tugas jurnal 1-10

7/28/2019 Tugas jurnal 1-10

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1. Wei Sheng Yan Jiu.2013 Mar;42(2):277-81.[Be based on the morphological and histological changes to study optimal dose of

TCDD induced cleft palate in mice embryo].

He X,Liu C,Pu Y,Gan L,Yuan X,Wei G,Fu Y.Source :http://www.ncbi.nlm.nih.gov/pubmed/23654107 Plastic Surgery of Chongqing Medical University Affiliated Children's Hospital, Ministry of Education

Key Laboratory of Child Development and Disorders, Chongqing 40014, [email protected]

Abstract

OBJECTIVE:

To define the optimal 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) dose based on the morphologicaland histological changes of fetal mice cleft palate induced by different TCDD doses.

METHODS:

The pregnant mice were randomly divided into five groups and 6 in each grouop, and were gavaged on

gestation day 10 (GD10). The control group were given 0.1 ml corn oil, and the experimental groups I, II ,III, IV were given 32, 28, 24, 20 microg/kg TCDD respectively. To weight pregnant mice and embryos,

record the number of live, cleft palate, dead and resorption fetal mice on GD 17.5. Another 15 pregnantmice were randomly divided into five groups (same as above) and 3 in each group. The coronal sections

of the fetal mice heads were prepared at GD 13.5, 14.5 and 15.5 respectively, stained with haematoxylin-eosin staining (HE) and observed by microscopy.

RESULTS:

No significant differences in embryonic weight and live fetuses weight in each group. Compared with thecontrol group,experimental groups I - III had small palate shelves (PS) and delayed palae shelves lift;the palate development and elevation in experimental group IV was similar to the control group. The

incidence of cleft palate in the experimental groups I - IV were 97.37%, 93.02%, 65.12%, 56.82%, andno cleft palate in the control group.

CONCLUSION:

The optimal dose of TCDD to induce cleft palate in C57BL/6J mice is 28 microg/kg.

Plant Foods Hum Nutr.1998;52(4):315-24.

Supplementary effect of spirulina on hematological status of ratsduring pregnancy and lactation.Kapoor R,Mehta U.Source :http://www.ncbi.nlm.nih.gov/pubmed/10426118Department of Home Science, Sri Sathya Sai Institute of Higher Learning Anantapur, Andhra Pradesh,India.

AbstractThe effect of Spirulina on iron status was assessed based on hemoglobin, packed cell volume, serum iron, totaliron binding capacity and ferritin levels of rats during pregnancy and lactation. Rats were fed 5 different kinds ofdiets (casein, Spirulina, wheat gluten, Spirulina + wheat gluten, Spirulina without additional vitamins andminerals) each providing 22 percent protein. Diets containing Spirulina alone or in combination with wheatgluten resulted in significantly higher iron storage and hemoglobin contents than casein and wheat gluten diets

during the first half of pregnancy and lactation. Wheat gluten diet result in the smallest increase in hemoglobinlevels and iron stores compared to other diets. The values of serum iron and iron binding capacity remainedunchanged with different diets. Spirulina appears to be effective in improving the iron status of rats duringpregnancy and lactation.
http://www.ncbi.nlm.nih.gov/pubmed/23654107http://www.ncbi.nlm.nih.gov/pubmed/23654107http://www.ncbi.nlm.nih.gov/pubmed?term=He%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=He%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Liu%20C%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Liu%20C%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Liu%20C%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Pu%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Pu%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Pu%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Gan%20L%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Gan%20L%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Gan%20L%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Yuan%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Yuan%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Yuan%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Wei%20G%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Wei%20G%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Wei%20G%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Fu%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Fu%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Fu%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed/23654107http://www.ncbi.nlm.nih.gov/pubmed/23654107http://www.ncbi.nlm.nih.gov/pubmed/23654107http://www.ncbi.nlm.nih.gov/pubmed/10426118http://www.ncbi.nlm.nih.gov/pubmed/10426118http://www.ncbi.nlm.nih.gov/pubmed?term=Kapoor%20R%5BAuthor%5D&cauthor=true&cauthor_uid=10426118http://www.ncbi.nlm.nih.gov/pubmed?term=Kapoor%20R%5BAuthor%5D&cauthor=true&cauthor_uid=10426118http://www.ncbi.nlm.nih.gov/pubmed?term=Mehta%20U%5BAuthor%5D&cauthor=true&cauthor_uid=10426118http://www.ncbi.nlm.nih.gov/pubmed?term=Mehta%20U%5BAuthor%5D&cauthor=true&cauthor_uid=10426118http://www.ncbi.nlm.nih.gov/pubmed?term=Mehta%20U%5BAuthor%5D&cauthor=true&cauthor_uid=10426118http://www.ncbi.nlm.nih.gov/pubmed/10426118http://www.ncbi.nlm.nih.gov/pubmed/10426118http://www.ncbi.nlm.nih.gov/pubmed/10426118http://www.ncbi.nlm.nih.gov/pubmed/10426118http://www.ncbi.nlm.nih.gov/pubmed?term=Mehta%20U%5BAuthor%5D&cauthor=true&cauthor_uid=10426118http://www.ncbi.nlm.nih.gov/pubmed?term=Kapoor%20R%5BAuthor%5D&cauthor=true&cauthor_uid=10426118http://www.ncbi.nlm.nih.gov/pubmed/10426118http://www.ncbi.nlm.nih.gov/pubmed/23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Fu%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Wei%20G%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Yuan%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Gan%20L%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Pu%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=Liu%20C%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed?term=He%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23654107http://www.ncbi.nlm.nih.gov/pubmed/23654107


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2. J Biol Chem.2013 May 10;288(19):13467-80. doi: 10.1074/jbc.M112.431775. Epub 2013 Apr 1.

TGF--activated kinase 1 (Tak1) mediates agonist-induced Smad activation and linker region

phosphorylation in embryonic craniofacial neural crest-derived cells.

Yumoto K,Thomas PS,Lane J,Matsuzaki K,Inagaki M,Ninomiya-Tsuji J,Scott GJ,Ray MK,IshiiM,Maxson R,Mishina Y,Kaartinen V.

Source :http://www.ncbi.nlm.nih.gov/pubmed/23546880 Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Ann Arbor, MI48109, USA.

Abstract

BACKGROUND:

The role of Smad-independent TGF- signaling in craniofacial development is poorly elucidated.

RESULTS:

In craniofacial mesenchymal cells, Tak1 regulates both R-Smad C-terminal and linker region

phosphorylation in TGF- signaling.CONCLUSION:

Tak1 plays an irreplaceable role in craniofacial ecto-mesenchyme during embryogenesis.

SIGNIFICANCE:

Understanding the mechanisms of TGF- signaling contributes to knowledge of pathogenetic mechanismsunderlying common craniofacial birth defects. Although the importance of TGF- superfamily signalingin craniofacial growth and patterning is well established, the precise details of its signaling mechanisms

are still poorly understood. This is in part because of the concentration of studies on the role of the Smad-dependent (so-called "canonical") signaling pathways relative to the Smad-independent ones in many

biological processes. Here, we have addressed the role of TGF--activated kinase 1 (Tak1, Map3k7), oneof the key mediators of Smad-independent (noncanonical) TGF- superfamily signaling in craniofacialdevelopment, by deleting Tak1 specifically in the neural crest lineage. Tak1-deficient mutants display a

round skull, hypoplastic maxilla and mandible, and cleft palate resulting from a failure of palatal shelvesto appropriately elevate and fuse. Our studies show that in neural crest-derived craniofacial ecto-mesenchymal cells, Tak1 is not only required for TGF-- and bone morphogenetic protein-induced p38Mapk activation but also plays a role in agonist-induced C-terminal and linker region phosphorylation of

the receptor-mediated R-Smads. Specifically, we demonstrate that the agonist-induced linker regionphosphorylation of Smad2 at Thr-220, which has been shown to be critical for full transcriptional activityof Smad2, is dependent on Tak1 activity and that in palatal mesenchymal cells TGFRI and Tak1 kinasesmediate both overlapping and distinct TGF-2-induced transcriptional responses. To summarize, ourresults suggest that in neural crest-derived ecto-mesenchymal cells, Tak1 provides a critical point ofintersection in a complex dialogue between the canonical and noncanonical arms of TGF- superfamilysignaling required for normal craniofacial development.

KEYWORDS:

Bone Morphogenetic Protein (BMP), Craniofacial Birth Defects, Craniofacial Development, Embryo,

Linker Region Phosphorylation, SMAD Transcription Factor, Transforming Growth Factor beta(TGFbeta)
http://www.ncbi.nlm.nih.gov/pubmed/23546880http://www.ncbi.nlm.nih.gov/pubmed/23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Yumoto%20K%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Yumoto%20K%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Thomas%20PS%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Thomas%20PS%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Thomas%20PS%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Lane%20J%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Lane%20J%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Lane%20J%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Matsuzaki%20K%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Matsuzaki%20K%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Matsuzaki%20K%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Inagaki%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Inagaki%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Inagaki%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ninomiya-Tsuji%20J%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ninomiya-Tsuji%20J%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ninomiya-Tsuji%20J%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Scott%20GJ%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Scott%20GJ%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Scott%20GJ%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ray%20MK%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ray%20MK%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ray%20MK%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ishii%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ishii%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ishii%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ishii%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Maxson%20R%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Maxson%20R%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Maxson%20R%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Mishina%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Mishina%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Mishina%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Kaartinen%20V%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Kaartinen%20V%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Kaartinen%20V%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed/23546880http://www.ncbi.nlm.nih.gov/pubmed/23546880http://www.ncbi.nlm.nih.gov/pubmed/23546880http://www.ncbi.nlm.nih.gov/pubmed/23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Kaartinen%20V%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Mishina%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Maxson%20R%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ishii%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ishii%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ray%20MK%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Scott%20GJ%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Ninomiya-Tsuji%20J%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Inagaki%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Matsuzaki%20K%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Lane%20J%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Thomas%20PS%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed?term=Yumoto%20K%5BAuthor%5D&cauthor=true&cauthor_uid=23546880http://www.ncbi.nlm.nih.gov/pubmed/23546880


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3. Food Chem Toxicol.2013 Jun;56:67-74. doi: 10.1016/j.fct.2013.02.003. Epub 2013 Feb 13.Dexamethasone alters epithelium proliferation and survival and suppresses Wnt/-catenin

signaling in developing cleft palate.

Hu X,Gao JH,Liao YJ,Tang SJ,Lu F.Source :http://www.ncbi.nlm.nih.gov/pubmed/23416130 Department of Plastic and Cosmetic Surgery, Nan Fang Hospital, Guangzhou 510515, People's Republic

of China.Abstract

Dexamethasone (Dex) contributes to a cleft palate, but the cellular and molecular mechanisms responsiblefor the deleterious effect on the developing palate are unclear. Wnt signaling is a causal mechanism ofDex-induced osteoporosis, so this study was conducted to determine whether Dex-induced cleft

palate may result from altered Wnt signaling. Administration of Dex to mice completely inhibitedcanonical Wnt/-catenin signaling and altered cell proliferation and apoptosis of the craniofacialepithelium in developing embryos. Thus, downregulated Wnt/-catenin signaling was associated withDex-induced cleft palate. Moreover, altered cell fate by Dex responsible for small palates, delaying shelfelevation and unfused palates was a crucial mechanism in cleft palate. Our findings help in elucidating the

mechanisms of Dex-induced cleft palate.

Plant Foods Hum Nutr.1993 Jan;43(1):29-35.

Effect of supplementation of blue green alga (Spirulina) onoutcome of pregnancy in rats.

Kapoor R,Mehta U.

Source :http://www.ncbi.nlm.nih.gov/pubmed/8464842

Department of Foods and Nutrition, Haryana Agricultural University, Hisar, India.

AbstractTo study the supplementary effect of Spirulina, pregnant rats were fed 5 different kinds of diets (casein,

Spirulina, wheat gluten, Spirulina + wheat gluten, Spirulina-without additional vitamins and minerals), eachproviding 22% protein during the period of pregnancy. The outcome of pregnancy was assessed from litter and

dams' weight and litter size. Maternal weight gain was found to be maximum with Spirulina + wheat gluten and

least with the wheat gluten diet. Rats receiving Spirulina containing diets produced significantly (p < 0.05)

higher litter size than those receiving casein and wheat gluten. In spite of having higher litter size, Spirulina

containing diet groups produced pups with birth weights comparable to those of casein. Spirulina appears to be

a good dietary supplement during pregnancy.
http://www.ncbi.nlm.nih.gov/pubmed/23416130http://www.ncbi.nlm.nih.gov/pubmed/23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Hu%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Hu%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Gao%20JH%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Gao%20JH%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Gao%20JH%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Liao%20YJ%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Liao%20YJ%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Liao%20YJ%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Tang%20SJ%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Tang%20SJ%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Tang%20SJ%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Lu%20F%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Lu%20F%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Lu%20F%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed/23416130http://www.ncbi.nlm.nih.gov/pubmed/23416130http://www.ncbi.nlm.nih.gov/pubmed/23416130http://www.ncbi.nlm.nih.gov/pubmed/8464842http://www.ncbi.nlm.nih.gov/pubmed/8464842http://www.ncbi.nlm.nih.gov/pubmed?term=Kapoor%20R%5BAuthor%5D&cauthor=true&cauthor_uid=8464842http://www.ncbi.nlm.nih.gov/pubmed?term=Kapoor%20R%5BAuthor%5D&cauthor=true&cauthor_uid=8464842http://www.ncbi.nlm.nih.gov/pubmed?term=Mehta%20U%5BAuthor%5D&cauthor=true&cauthor_uid=8464842http://www.ncbi.nlm.nih.gov/pubmed?term=Mehta%20U%5BAuthor%5D&cauthor=true&cauthor_uid=8464842http://www.ncbi.nlm.nih.gov/pubmed?term=Mehta%20U%5BAuthor%5D&cauthor=true&cauthor_uid=8464842http://www.ncbi.nlm.nih.gov/pubmed/8464842http://www.ncbi.nlm.nih.gov/pubmed/8464842http://www.ncbi.nlm.nih.gov/pubmed/8464842http://www.ncbi.nlm.nih.gov/pubmed/8464842http://www.ncbi.nlm.nih.gov/pubmed?term=Mehta%20U%5BAuthor%5D&cauthor=true&cauthor_uid=8464842http://www.ncbi.nlm.nih.gov/pubmed?term=Kapoor%20R%5BAuthor%5D&cauthor=true&cauthor_uid=8464842http://www.ncbi.nlm.nih.gov/pubmed/8464842http://www.ncbi.nlm.nih.gov/pubmed/23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Lu%20F%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Tang%20SJ%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Liao%20YJ%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Gao%20JH%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed?term=Hu%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23416130http://www.ncbi.nlm.nih.gov/pubmed/23416130


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4. Teratology.1990 Dec;42(6):597-610.Retinoic acid-induced alterations in the expression of growth factors in embryonic mouse palatal

shelves.

Abbott BD,Birnbaum LS.Source :http://www.ncbi.nlm.nih.gov/pubmed/2087681 Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle

Park, North Carolina 27709.Abstract

Retinoic acid (RA) is teratogenic in many species, producing multiple malformations, including cleftpalate. The effects of RA which lead to cleft palate vary depending on the stage of development exposed.After exposure of embryonic mice to RA on gestation day (GD) 10, abnormally small palatal shelvesform. After exposure on GD 12 shelves of normal size form, but fail to fuse, as the medial cells proliferate

and differentiate into a nasal-like epithelium. Growth factors and their receptors play an important role inregulating development, and the expression of EGF receptors, EGF, TGF-alpha, TFG-beta 1, and TGF-

beta 2 has been reported in the mouse embryo. In a variety of cell types in culture, these growth factorsare capable of regulating proliferation, differentiation, expression of matrix proteins, and other cellular

events including epithelial-mesenchymal transformations. The present study examinesimmunohistochemically the expression of EGF, TGF-alpha, TGF-beta 1, and TGF-beta 2 in the control

embryonic palatal shelves from GD 12 to 15 and the effects of RA treatment on GD 10 or 12 on theirexpression on GD 14 and 16. These growth factors were shown to have specific temporal and spatialexpression in the palatal shelf. With advancing development the levels of TGF-alpha decreased while the

expression of EGF increased. TGF-beta 2 localization became regional by GD 14-15, with higher levelsfound in epithelial cells and chondrogenic mesenchyme. TGF-beta 1 occurred in epithelial andmesenchymal cells and distribution did not change substantially with advancing development. RA

exposure altered the expression of TFG-alpha, TGF-beta 1, and TGF-beta 2, but significant effects onEGF were not found. The effects on TGF-alpha and TGF-beta 1 expression were dependent on the

gestational age exposed. Levels of TGF-alpha on GD 14 decreased after RA exposure on GD 10, butincreased after GD 12 exposure. TGF-beta 1 expression in the mesenchyme was increased after exposureon GD 12, but was unaffected by RA on GD 10. After exposure on either day, the levels of TGF-beta 2

increased in GD 14 nasal epithelial cells. Acting in concert, growth factors could regulate events critical

to formation of the secondary palate, including cessation of medial epithelial cell proliferation, synthesisof extracellular matrix proteins in the mesenchyme, programmed cell death of medial epithelial

peridermal cells, and transformation of basal epithelial medial cells to mesenchymal cells.(ABSTRACTTRUNCATED AT 400 WORDS)

Minerva Stomatol.1992 Dec;41(12):557-66.

[A current update on the etiopathogenesis of palatoschisis].

[Article in Italian]

Pierleoni P,Tollaro I,Baccetti T,Franchi L.Source :http://www.ncbi.nlm.nih.gov/pubmed/1301490

Facolt di Medicina e Chirurgia, Istituto di Odonto-Gnato-Stomatologia, Universit degli Studi di

Firenze.Abstract

By means of a review of the most recent literature, the authors report on "state of the art" about etiologyand pathogenesis of cleft palate. Epithelial-mesenchymal interactions regulating growth and orientation of

palatal shelves, as well as teratogenic effects on such ultrastructural development control by endogenousand exogenous substances, are described.
http://www.ncbi.nlm.nih.gov/pubmed/2087681http://www.ncbi.nlm.nih.gov/pubmed/2087681http://www.ncbi.nlm.nih.gov/pubmed?term=Abbott%20BD%5BAuthor%5D&cauthor=true&cauthor_uid=2087681http://www.ncbi.nlm.nih.gov/pubmed?term=Abbott%20BD%5BAuthor%5D&cauthor=true&cauthor_uid=2087681http://www.ncbi.nlm.nih.gov/pubmed?term=Birnbaum%20LS%5BAuthor%5D&cauthor=true&cauthor_uid=2087681http://www.ncbi.nlm.nih.gov/pubmed?term=Birnbaum%20LS%5BAuthor%5D&cauthor=true&cauthor_uid=2087681http://www.ncbi.nlm.nih.gov/pubmed?term=Birnbaum%20LS%5BAuthor%5D&cauthor=true&cauthor_uid=2087681http://www.ncbi.nlm.nih.gov/pubmed/2087681http://www.ncbi.nlm.nih.gov/pubmed/2087681http://www.ncbi.nlm.nih.gov/pubmed/2087681http://www.ncbi.nlm.nih.gov/pubmed/1301490http://www.ncbi.nlm.nih.gov/pubmed/1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Pierleoni%20P%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Pierleoni%20P%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Tollaro%20I%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Tollaro%20I%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Tollaro%20I%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Baccetti%20T%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Baccetti%20T%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Baccetti%20T%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Franchi%20L%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Franchi%20L%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Franchi%20L%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed/1301490http://www.ncbi.nlm.nih.gov/pubmed/1301490http://www.ncbi.nlm.nih.gov/pubmed/1301490http://www.ncbi.nlm.nih.gov/pubmed/1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Franchi%20L%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Baccetti%20T%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Tollaro%20I%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed?term=Pierleoni%20P%5BAuthor%5D&cauthor=true&cauthor_uid=1301490http://www.ncbi.nlm.nih.gov/pubmed/1301490http://www.ncbi.nlm.nih.gov/pubmed/2087681http://www.ncbi.nlm.nih.gov/pubmed?term=Birnbaum%20LS%5BAuthor%5D&cauthor=true&cauthor_uid=2087681http://www.ncbi.nlm.nih.gov/pubmed?term=Abbott%20BD%5BAuthor%5D&cauthor=true&cauthor_uid=2087681http://www.ncbi.nlm.nih.gov/pubmed/2087681


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5. Zhonghua Kou Qiang Yi Xue Za Zhi.2003 May;38(3):185-7.[Study on etiology of retinoic acid-induced cleft palate in mouse].

Huang HZ,L BH,Chen YY,Liao GQ.Source :http://www.ncbi.nlm.nih.gov/pubmed/12887794

Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital, Sun Yet-sen University,Guangzhou 510120, China.

AbstractOBJECTIVE:To investigate the morphologic changes of embryonic palatal development exposed toretinoic acid (RA) in mouse, and to detect the significance of the expression of TGFbeta1, TGFbeta3,EGF and BCL2.METHODS:The stage of palatal development was examined by light microscopy. S-Pimmunohistochemistry and in-situ hybridization was used to detect spatio-temporal patterns of

expression of TGFbeta1, TGFbeta3, EGF and BCL2 in embryonic palate.RESULTS:The fetus exposed to RA resulted in formation of small palatal shelves without contact and

fusion of each other to form and intact palate. RA can regulate the embryonic palatal expression of genesinvolved in RA-induced cleft palate.

CONCLUSIONS:RA can inhibit the proliferation of MEPM cell to form small palatal shelves andinduce abnormal differentiation of MEE cell causing the bi-palatal shelves no contact and fuse with each

other, then induce the formation of cleft palate. RA can regulate the spatio-temporal patterns ofexpression of TGFbeta1, TGFbeta3 and EGF in embryonic palatal processes and the change of specialexpression of these genes in embryonic palatal processes are involved in RA-induced cleft palate.

Central European Journal of Medicine

April 2010, Volume 5,Issue 2, pp 235-242

Is adequate and balanced nutrition during pregnancy more effective than iron and folic acidsupplements?

Funda Elmacioglu,

Bulent Surucu,

Tayfun Alper, Aliye Ozenoglu,

Serdal Ugurlu

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AbstractTo provide instruction for pregnant women regarding adequate and balanced nutrition and determine whether iron and

folic acid supplementation is essential. The research was an experimental clinical intervention. The study was conducted

between March 2004 and May 2005 with 80 pregnant volunteers. The study participants were in their 16th to 24th weeks

of pregnancy; all participants were healthy, carried only one fetus, and successfully completed their pregnancy. All

participants were instructed about adequate and balanced nutrition. Until the participants gave birth, 40 (Group 1)

consumed an iron-rich diet that was equivalent to the inclusion of a supplement containing 100 mg Ferro III plus 0,35 mg

folic acid; the other group (Group 2) was also instructed in proper nutrition and was given by a gynecologist 1 tablet (100
http://www.ncbi.nlm.nih.gov/pubmed/12887794http://www.ncbi.nlm.nih.gov/pubmed/12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Huang%20HZ%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Huang%20HZ%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=L%C3%BC%20BH%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=L%C3%BC%20BH%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=L%C3%BC%20BH%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Chen%20YY%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Chen%20YY%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Chen%20YY%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Liao%20GQ%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Liao%20GQ%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Liao%20GQ%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed/12887794http://www.ncbi.nlm.nih.gov/pubmed/12887794http://www.ncbi.nlm.nih.gov/pubmed/12887794http://link.springer.com/journal/11536http://link.springer.com/journal/11536http://link.springer.com/journal/11536/5/2/page/1http://link.springer.com/journal/11536/5/2/page/1http://link.springer.com/journal/11536/5/2/page/1http://link.springer.com/search?facet-author=%22Funda+Elmacioglu%22http://link.springer.com/search?facet-author=%22Bulent+Surucu%22http://link.springer.com/search?facet-author=%22Tayfun+Alper%22http://link.springer.com/search?facet-author=%22Aliye+Ozenoglu%22http://link.springer.com/search?facet-author=%22Serdal+Ugurlu%22http://link.springer.com/accesspage/article/10.2478/s11536-009-0099-1?coverImageUrl=%2Fstatic-content%2Fcovers%2Fjournals%2F856%2F11536.jpghttp://link.springer.com/accesspage/article/10.2478/s11536-009-0099-1?coverImageUrl=%2Fstatic-content%2Fcovers%2Fjournals%2F856%2F11536.jpghttp://link.springer.com/accesspage/article/10.2478/s11536-009-0099-1?coverImageUrl=%2Fstatic-content%2Fcovers%2Fjournals%2F856%2F11536.jpghttp://link.springer.com/search?facet-author=%22Serdal+Ugurlu%22http://link.springer.com/search?facet-author=%22Aliye+Ozenoglu%22http://link.springer.com/search?facet-author=%22Tayfun+Alper%22http://link.springer.com/search?facet-author=%22Bulent+Surucu%22http://link.springer.com/search?facet-author=%22Funda+Elmacioglu%22http://link.springer.com/journal/11536/5/2/page/1http://link.springer.com/journal/11536http://www.ncbi.nlm.nih.gov/pubmed/12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Liao%20GQ%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Chen%20YY%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=L%C3%BC%20BH%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed?term=Huang%20HZ%5BAuthor%5D&cauthor=true&cauthor_uid=12887794http://www.ncbi.nlm.nih.gov/pubmed/12887794


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mg) Ferro III hydroxide polymaltose complex and iron pharmaceutical with 0,35 mg folic acid (Maltofer Fol). In both

groups, before and after the instruction, consumption frequency was noted, and the levels of serum ferritin, serum iron,

total iron-binding capacity, folic acid, and vitamin B12 in the blood were determined at monthly intervals. Between the

two groups, no statistical difference was found with regard to age, number of pregnancies, weight before pregnancy, body

mass index (BMI) before pregnancy, and weight of the newborn (p>0,05). At the end of the study, the hemoglobin,

hematocrit, and serum ferritin levels decreased considerably in both groups compared to the initial values (p0,05). The

comparison of Group I and Group II in terms of nutritional status (average energy and food consumption) in the pre-instruction and post-instruction periods revealed that intake of total protein, heme protein, dietary fiber, folic acid,

carotene, vitamins A, B1, B2, B6, C, and B12, potassium, calcium, phosphorus, iron, and zinc was higher in Group I in the

post-instruction period (p=0.000); no statistically significant change in nutritional status during pregnancy was observed in

Group II. Conclusion: Medical diet programs with iron sources are examined in association with food consumption.

Assessment of hematological results suggests that, during pregnancy, each patient should receive a specific dose, rather

than a routine dose, of iron and folic acid.

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important medical, social or educational needs. The prevalence of chromosomal anomalies was 3.6 per1,000 births, contributing 28% of stillbirths/fetal deaths from 20 weeks gestation with congenital

anomaly, and 48% of all TOPFA. Congenital heart defects (CHD) were the most common non-chromosomal subgroup, at 6.5 per 1,000 births, followed by limb defects (3.8 per 1,000), anomalies ofurinary system (3.1 per 1,000) and nervous system defects (2.3 per 1,000). In 2004, perinatal mortalityassociated with congenital anomaly was 0.93 per 1,000 births, and TOPFA 4.4 per 1,000 births, with

considerable country variation. Primary prevention of congenital anomalies in the population based oncontrolling environmental risk factors is a crucial policy priority, including preconceptional care andwhole population approaches.Lancet.2009 Nov 21;374(9703):1773-85. doi: 10.1016/S0140-6736(09)60695-4. Epub 2009 Sep 9.

Cleft lip and palate.

Mossey PA,Little J,Munger RG,Dixon MJ,Shaw WC.Source :http://www.ncbi.nlm.nih.gov/pubmed/19747722/

Department of Dental and Oral Health, University of Dundee, Dental Hospital and School, Dundee, UK.

[email protected]

Abstract

Clefts of the lip and palate are generally divided into two groups, isolated cleft palate and cleft lip with orwithout cleft palate, representing a heterogeneous group of disorders affecting the lips and oral cavity.

These defects arise in about 1.7 per 1000 liveborn babies, with ethnic and geographic variation. Effects onspeech, hearing, appearance, and psychology can lead to longlasting adverse outcomes for health andsocial integration. Typically, children with these disorders need multidisciplinary care from birth to

adulthood and have higher morbidity and mortality throughout life than do unaffected individuals. ThisSeminar describes embryological developmental processes, epidemiology, known environmental andgenetic risk factors, and their interaction. Although access to care has increased in recent years, especially

in developing countries, quality of care still varies substantially. Prevention is the ultimate objective forclefts of the lip and palate, and a prerequisite of this aim is to elucidate causes of the disorders.

Technological advances and international collaborations have yielded some successes.Am J Hum Genet.1996 Jan;58(1):182-90.

8. Familial recurrence-pattern analysis of nonsyndromic isolated cleft palate--a DanishRegistry study.

Christensen K,Mitchell LE.Source :http://www.ncbi.nlm.nih.gov/pubmed/8554055/ Steno Institute of Public Health, Department of Epidemiology and Social Medicine, Aarhus University,Denmark.

Abstract

The finding of an association between genetic variation at the transforming growth-factor alpha (TGFA)locus and nonsyndromic isolated cleft palate (CP) represents a potentially important breakthrough in ourunderstanding of this condition. The present study was undertaken to assess the feasibility of detectinglinkage to putative CP-susceptibility loci, such as TGFA. To this end, the familial recurrence pattern for

CP was evaluated to determine the most likely mode of inheritance for this condition. The study tookadvantage of the high ascertainment and uniform registration of CP in Denmark. In addition, the study

utilized estimates of familial recurrence that were obtained by register linkage and, hence, were not

subject to either recall bias or the potentially biasing influence of nonresponders. The recurrence risks forfirst-, second-, and third-degree relatives of 1,364 nonsyndromic CP probands were estimated to be 2.74%(72/2,628), 0.28% (3/1,068), and 0.00% (0/360), respectively. These estimates are close to publishedestimates based on questionnaire and interview data. The population prevalence for nonsyndromic CP

was, however, found to be considerable higher than usually reported (0.058% [1,456/2,523,023]).Analyses of these and previously published data, using the method presented by Risch, indicated thatmajor-locus or additive multilocus inheritance of CP is unlikely. The familial recurrence pattern was,however, consistent with CP being determined by several interacting loci. Under such a model, a singlelocus accounting for more than a sixfold increase in the risk to first-degree relatives of CP probands is
http://www.ncbi.nlm.nih.gov/pubmed/19747722/http://www.ncbi.nlm.nih.gov/pubmed/19747722/http://www.ncbi.nlm.nih.gov/pubmed?term=Mossey%20PA%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Mossey%20PA%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Little%20J%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Little%20J%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Little%20J%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Munger%20RG%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Munger%20RG%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Munger%20RG%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Dixon%20MJ%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Dixon%20MJ%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Dixon%20MJ%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Shaw%20WC%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Shaw%20WC%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Shaw%20WC%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed/19747722/http://www.ncbi.nlm.nih.gov/pubmed/19747722/http://www.ncbi.nlm.nih.gov/pubmed/19747722/http://www.ncbi.nlm.nih.gov/pubmed/8554055/http://www.ncbi.nlm.nih.gov/pubmed/8554055/http://www.ncbi.nlm.nih.gov/pubmed?term=Christensen%20K%5BAuthor%5D&cauthor=true&cauthor_uid=8554055http://www.ncbi.nlm.nih.gov/pubmed?term=Christensen%20K%5BAuthor%5D&cauthor=true&cauthor_uid=8554055http://www.ncbi.nlm.nih.gov/pubmed?term=Mitchell%20LE%5BAuthor%5D&cauthor=true&cauthor_uid=8554055http://www.ncbi.nlm.nih.gov/pubmed?term=Mitchell%20LE%5BAuthor%5D&cauthor=true&cauthor_uid=8554055http://www.ncbi.nlm.nih.gov/pubmed?term=Mitchell%20LE%5BAuthor%5D&cauthor=true&cauthor_uid=8554055http://www.ncbi.nlm.nih.gov/pubmed/8554055/http://www.ncbi.nlm.nih.gov/pubmed/8554055/http://www.ncbi.nlm.nih.gov/pubmed/8554055/http://www.ncbi.nlm.nih.gov/pubmed/8554055/http://www.ncbi.nlm.nih.gov/pubmed?term=Mitchell%20LE%5BAuthor%5D&cauthor=true&cauthor_uid=8554055http://www.ncbi.nlm.nih.gov/pubmed?term=Christensen%20K%5BAuthor%5D&cauthor=true&cauthor_uid=8554055http://www.ncbi.nlm.nih.gov/pubmed/8554055/http://www.ncbi.nlm.nih.gov/pubmed/19747722/http://www.ncbi.nlm.nih.gov/pubmed?term=Shaw%20WC%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Dixon%20MJ%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Munger%20RG%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Little%20J%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed?term=Mossey%20PA%5BAuthor%5D&cauthor=true&cauthor_uid=19747722http://www.ncbi.nlm.nih.gov/pubmed/19747722/


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unlikely, whereas a single locus accounting for a threefold increase provided a good fit to the data. Such alocus could be detected in a realistic sample of affected sib pairs.

9. Am J Hum Genet. 1992 August; 51(2): 323332.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/

PMCID: PMC1682664

Mode of inheritance of nonsyndromic cleft lip with or without cleft palate: a reanalysis.

L E MitchellandN RischAuthor information Copyright and License information

This article has beencited byother articles in PMC.Abstract

Nonsyndromic cleft lip with or without cleft palate (CL +/- P) is traditionally recognized as a

multifactorial threshold trait (MFT). Recently, however, evidence for the involvement of a major gene inthe etiology of CL +/- P has been reported. To assess the potential for major-gene involvement in the

etiology of this trait, familial recurrence patterns from several family studies of CL +/- P were reanalyzed.The recurrence patterns in first-degree relatives of CL +/- P probands were found to be compatible withthe expectations for either an MFT or a generalized single-major-locus (gSML) trait. The use of multiple

thresholds based on proband sex, defect bilaterality, or palatal involvement did not help to discriminatebetween these models. However, the pattern of recurrence among MZ twins and more remote relatives ofCL +/- P probands is not consistent with gSML inheritance but is compatible with either an MFT modelor a model specifying multiple interacting loci. For such a model, no single locus can account for more

than a sixfold increase in risk to first-degree relatives. These findings have important implications withregard to the feasibility of detecting linkage to loci conferring susceptibility to CL +/- P.B-ENT.2006;2 Suppl 4:11-9.

Embryology and epidemiology of cleft lip and palate.

Bernheim N,Georges M,Malevez C,De Mey A,Mansbach A.Source :http://www.ncbi.nlm.nih.gov/pubmed/17366840

Department of Otorhinolaryngology, Head and Neck Surgery, The Cleft Lip and Palate Team, HpitalUniversitaire des Enfants Reine Fabiola, Brussels, Belgium. [email protected]

Abstract

Craniofacial anomalies, in particular cleft lip and palate, are major human birth defects with a worldwide

frequency of 1 in 700 and substantial clinical impact. This article reviews the embryology of the face, lip,and palate to enhance the understanding of the pathogenesis of these lesions, with particular attention to

the period of susceptibility during gestation, complexity, and the factors that may influence theirdevelopment. It includes an overview of the prevalence and environmental and genetic causes of cleft lip-with or without cleft palate- and cleft palate.

PMID:

10. Int J Pediatr Otorhinolaryngol.2009 Jul;73(7):993-7. doi: 10.1016/j.ijporl.2009.03.027. Epub2009 May 13.

Cleft lip and palate treatment of 530 children over a decade in a single centre.

Vlastos IM,Koudoumnakis E,Houlakis M,Nasika M,Griva M,Stylogianni E.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pubmed/?term=Mitchell%20LE%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Mitchell%20LE%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Risch%20N%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Risch%20N%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Risch%20N%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/citedby/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/citedby/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/citedby/http://www.ncbi.nlm.nih.gov/pubmed/17366840http://www.ncbi.nlm.nih.gov/pubmed/17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Bernheim%20N%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Bernheim%20N%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Georges%20M%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Georges%20M%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Georges%20M%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Malevez%20C%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Malevez%20C%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Malevez%20C%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=De%20Mey%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=De%20Mey%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=De%20Mey%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Mansbach%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Mansbach%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Mansbach%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed/17366840http://www.ncbi.nlm.nih.gov/pubmed/17366840http://www.ncbi.nlm.nih.gov/pubmed/17366840http://www.ncbi.nlm.nih.gov/pubmed/19443049http://www.ncbi.nlm.nih.gov/pubmed/19443049http://www.ncbi.nlm.nih.gov/pubmed/19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Vlastos%20IM%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Vlastos%20IM%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Koudoumnakis%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Koudoumnakis%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Koudoumnakis%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Houlakis%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Houlakis%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Houlakis%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Nasika%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Nasika%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Nasika%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Griva%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Griva%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Griva%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Stylogianni%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Stylogianni%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Stylogianni%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Stylogianni%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Griva%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Nasika%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Houlakis%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Koudoumnakis%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed?term=Vlastos%20IM%5BAuthor%5D&cauthor=true&cauthor_uid=19443049http://www.ncbi.nlm.nih.gov/pubmed/19443049http://www.ncbi.nlm.nih.gov/pubmed/17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Mansbach%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=De%20Mey%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Malevez%20C%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Georges%20M%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed?term=Bernheim%20N%5BAuthor%5D&cauthor=true&cauthor_uid=17366840http://www.ncbi.nlm.nih.gov/pubmed/17366840http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/citedby/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/http://www.ncbi.nlm.nih.gov/pubmed/?term=Risch%20N%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Mitchell%20LE%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682664/


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Center of Craniofacial Anomalies, Department of Otolaryngology, Head and Neck Surgery, Aghia Sophia

Children Hospital of Athens, Greece. [email protected]

Abstract

OBJECTIVE:

We sought to evaluate the process of care and the outcomes of cleft lip and palate operations carried by a

multidisciplinary team at a centre of craniofacial anomalies with a high patients' volume.METHODS:

A retrospective review of all cleft lips and/or palates cases treated in the centre from 1995 to 2007 wasperformed. Direct and long term complication rates, clinical, audiologic, speech intelligibility and dentalarch assessments were analyzed.

RESULTS:

A total of 530 children have been operated this period in the centre (64 isolated cleft lip closures). Adetailed presentation of the outcomes is performed in relation to the various types of cleft lip and palates.

The majority of parents (70%) reported very good or excellent results 2-5 years after the lip closure withthe Millard technique, although those with bilateral clefts were significantly less satisfied (P


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an important effort in terms of social organization as well as economical costs for the health care system.In Italy, the health care costs for approximately 800 children born with orofacial clefting per year has

been estimated at around 150 billion Lire (80 million Euros). The etiology of OC is complex andheterogeneous both for isolated and associated defects; causes linked to environment, genetics and gene-environment interaction are known, although there is still a lot to do, especially in clarifying the role ofgenetics in producing susceptibility to the environment. Four categories of genes for which there are

results suggestive of a genetic susceptibility to OCs are: 1) genes expressed in a particular area of theembryo or in a particular period of the palatine arch development, such as the transforming growth factorsalpha and beta (TGF alpha, TGF beta 2, TGF beta 3); 2) genes having biological activities linked to theOC's pathogenesis without direct involvement (e.g. the retinoic acid receptor (RARA), themethylenetetrahydrofolate reductase receptor (MTHFR) and the folic acid receptor (FOLR1); 3) genes orlocus identified in experimental animals as the homeotic genes MSX-1 and MSX-2; 4) genes involved in

the interaction with the xenobiotics metabolism as those in P-450 cytochrome system. Severalenvironmental factors have been implicated in the OC etiology; among those, the folic acid

supplementation during the periconceptional period that was found effective in the prevention of neuraltube defects. In fact, folic acid deficiency may be responsible for different malformations through a

common mechanism that interferes with the embryonic development, depending on the maternal orembryo genotype. Further investigation is required to study in depth how the genotype would modify the

role of environmental factors like folic acid. Well-designed and conducted epidemiological studies seemto be able to give worthwhile information. Studies carried out in Europe on these issues are a few,

particularly those on gene-environment interaction. Recent results obtained in molecular biology and the

availability of wealth of data can allow to perform ad hoc investigations, being important not only for thebasic research but also for their public health implications. For this objective a specific scientific networkat the European level has been set by the European Science Foundation (ESF), whose first step will be to

establish consistent case ascertainment and data collection across Europe and to develop standardizedprotocols and methods of analysis. It is hoped that in the longer term such multicentre collaborative

research will enable combined analysis and lead to the identification of genetic susceptibility to certainenvironmental factors, including nutrition. Such studies would inform the current debate about theefficacy of folic acid and other nutritional factors in prevention of disease in the developing embryo.

Subsequent public health measures targeted according to risk might reduce the prevalence of disorders

such as orofacial clefting.

12.Am Fam Physician.1992 Oct;46(4):1211-21.Cleft lip and cleft palate.

Yetter JF 3rd.Source :http://www.ncbi.nlm.nih.gov/pubmed/1414884 Madigan Army Medical Center, Tacoma, Washington.

Abstract

The birth of a child with a cleft lip or a cleft palate, or both, can be traumatic to the family. Although

referral to a multidisciplinary team experienced in craniofacial abnormalities is essential, the family

physician can reduce the impact on the family by providing antenatal diagnosis and continued care of theentire family after diagnosis, during initial feeding and bonding difficulties and throughout the manyyears of surgical and speech therapy.

Cleft Lip and Palate

http://www.nlm.nih.gov/medlineplus/cleftlipandpalate.html Cleft lip and cleft palate arebirth defectsthat occur when a baby's lip or mouth do not form properly.They happen early during pregnancy. A baby can have a cleft lip, a cleft palate, or both.
http://www.ncbi.nlm.nih.gov/pubmed/1414884http://www.ncbi.nlm.nih.gov/pubmed/1414884http://www.ncbi.nlm.nih.gov/pubmed/1414884http://www.ncbi.nlm.nih.gov/pubmed?term=Yetter%20JF%203rd%5BAuthor%5D&cauthor=true&cauthor_uid=1414884http://www.ncbi.nlm.nih.gov/pubmed?term=Yetter%20JF%203rd%5BAuthor%5D&cauthor=true&cauthor_uid=1414884http://www.ncbi.nlm.nih.gov/pubmed/1414884http://www.ncbi.nlm.nih.gov/pubmed/1414884http://www.ncbi.nlm.nih.gov/pubmed/1414884http://www.nlm.nih.gov/medlineplus/cleftlipandpalate.htmlhttp://www.nlm.nih.gov/medlineplus/cleftlipandpalate.htmlhttp://www.nlm.nih.gov/medlineplus/birthdefects.htmlhttp://www.nlm.nih.gov/medlineplus/birthdefects.htmlhttp://www.nlm.nih.gov/medlineplus/birthdefects.htmlhttp://www.nlm.nih.gov/medlineplus/birthdefects.htmlhttp://www.nlm.nih.gov/medlineplus/cleftlipandpalate.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/1414884http://www.ncbi.nlm.nih.gov/pubmed?term=Yetter%20JF%203rd%5BAuthor%5D&cauthor=true&cauthor_uid=1414884http://www.ncbi.nlm.nih.gov/pubmed/1414884


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A cleft lip happens if the tissue that makes up the lip does not join completely before birth. This causes anopening in the upper lip. The opening can be a small slit or a large opening that goes through the lip into

the nose. It can be on one or both sides of the lip or, rarely, in the middle of the lip.Children with a cleft lip also can have a cleft palate. The roof of the mouth is called the "palate." With acleft palate, the tissue that makes up the roof of the mouth does not join correctly. Babies may have boththe front and back parts of the palate open, or they may have only one part open.

Children with a cleft lip or a cleft palate often have problems with feeding and talking. They also mighthave ear infections, hearing loss, and problems with their teeth.Often, surgery can close the lip and palate. Cleft lip surgery is usually done before age 12 months, andcleft palate surgery is done before 18 months. Many children have other complications. They may needadditional surgeries, dental and orthodontic care, and speech therapy as they get older. With treatment,most children with clefts do well and lead a healthy life.

13.Cleft lip and cleft palate :http://www.marchofdimes.com/baby/birth-defects.aspx#InDepthTabLong_1618

A cleft lip is a birth defect in which a baby's upper lip doesnt form completely and has an opening in it.

A cleftpalate is a similar birth defect in which a babys palate (roof of the mouth) doesnt formcompletely and has an opening in it. These birth defects are called oral clefts.

How does a cleft lip affect ababys face?Some babies with cleft lip have just a small notch in the upper lip. Others have a complete opening or

hole in the lip that goes through the upper gum to the bottom of the nose. A cleft lip can happen on one or

both sides of a babys mouth.

How does a cleft palate affect ababys mouth?A cleft palate can affect the soft palate (the soft tissue at the back of the roof of the mouth) or the hard

palate (the bony front part of the roof of the mouth). A cleft palate can happen on one or both sides of ababys palate.

Do cleft lip and cleft palate always happen together?No. Some babies have just a cleft lip. But most babies with a cleft lip also have a cleft palate. Some

babies have only a cleft palate, which is called an isolated cleft palate.

What problems can oral clefts cause?

Babies and children with oral clefts may have: Feeding problems

Ear infections and hearing loss

Speech problems

Dental problemsWhen do oral clefts happen?Oral clefts happen very early inpregnancy. Your babys lips are formed by about 6 weeks of pregnancy.Your babys palate is formed by about 10 weeks of pregnancy. Oral clefts happen when your babys lipsor palate or both dont form completely.
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What causes oral clefts?Were not sure what causes oral clefts. Some possible causes are: Changes in your babys genes. Genes are part of your babys cells that store instructions for the way

the body grows and works. They provide the basic plan for how your baby develops. Genes arepassed from parents to children.

Not getting enoughfolic acidbefore pregnancy. Folic acid is a vitamin that can help protect yourbaby from birth defects of the brain and spine called neural tube defects. It also may reduce the riskof oral clefts by about 25 percent.

Taking certain medicines, like anti-seizure medicine, during pregnancy

Smokingduring pregnancy. Smoking causes 1 in 5 (20 percent) oral clefts.

Drinking alcoholduring pregnancy

Having certain infections during pregnancyCan oral clefts be prevented?

Not all clefts can be prevented. But there are things you can do to help reduce your chances of having ababy with an oral cleft:

Before pregnancy, get apreconception checkup. This is a medical checkup to help make sure youare healthy before you get pregnant.

Before pregnancy, take a multivitamin with 400 micrograms of folic acid in it every day. During pregnancy, take a prenatal vitamin with 600 micrograms of folic acid in it every day. Talk to yourproviderto make sure any medicine you take is safe during pregnancy.

Your provider may want to switch you to a different medicine that is safe during pregnancy.

Dont smoke. Dont drink alcohol. Getearlyandregular prenatal care.

How are oral clefts treated?

In most cases, oral clefts can be repaired by surgery. Each baby is unique, but surgery to repair cleft lipusually is done at 10 to 12 weeks of age. Surgery for cleft palate usually is done between 9 and 18 monthsof age. Your child may need more surgery for oral clefts as he grows.

Your baby gets treated by a team of specialists. Most teams include: Pediatrician. This is a doctor who has special training in taking care of babies and children.

Plastic surgeon. This is a doctor who repairs or rebuilds parts of the body to improve how theywork and look.

Pediatric dentist. This is a dentist who has special training to care for the teeth of babies andchildren.

Orthodontist. This is a dentist who fixes tooth defects and straightens teeth with braces and othermethods.

Otolaryngologist or ear, nose and throat specialist (also called ENT). This is a doctor who treats

problems of the ears, nose and throat.

Speech or language specialist. This is a person trained to help with speech problems.

Audiologist. This is a person trained to measurehearing lossand fit hearing aids.

Genetic counselor. This is a person trained to know about genetics, birth defects and other medicalproblems that run in families.

Social worker. This is a person trained to help find resources and programs, such as health care andspecial services, for people with disabilities.

How common are oral clefts?About 6,800 babies in the United States are born with oral clefts each year.

Cleft lip and cleft palate affects about 4,200 babies each year. It is more common in Asians andcertain Native Americans.
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Nearly 2,600 babies are born with isolated cleft palate each year. Isolated cleft palate affects babiesof all races about the same.

Can other birth defects happen along with oral clefts?Yes. There are about 400 health conditions (called syndromes) that are related to oral clefts. If your babyhas an oral cleft, his provider checks him thoroughly for other birth defects soon after birth.

Are oral clefts more common in some families?Yes. If you have family members with oral clefts, you may be more likely to have a baby with an oralcleft. If neither you nor your partner has a cleft but your baby does, and if your baby doesnt have anykind of syndrome, the chance of you having another baby with a cleft is about 2 to 5 out of 100 (2 to 5

percent).

14. Centers for Disease Control and Prevention

http://www.nlm.nih.gov/medlineplus/craniofacialabnormalities.html Craniofacial is a medical term that relates to the bones of the skull and face. Craniofacial abnormalitiesarebirth defectsof the face or head. Some, likecleft lip and palate, are among the most common of all

birth defects. Others are very rare. Most of them affect how a person's face or head looks. These

conditions may also affect other parts of the body.Treatment depends on the type of problem. Plastic and reconstructive surgery may help the person'sappearance.

Arch Dis Child. 1987 July; 62(7): 717720.PMCID: PMC1779220

Epidemiology of facial clefts.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/

J WomersleyandD H StoneCopyright and License information This article has beencited byother articles in PMC.

Abstract

Data from the Glasgow Register of Congenital Malformations were used to investigate the epidemiology

of congenital facial clefts over the period 1974-85. Facial clefts were registered in 247 infantsrepresenting a prevalence of 1.56 per 1000 total births. Cleft palate was more common than cleft lip, withcleft lip and palate occupying an intermediate position. More than half of the infants with facial clefts hadassociated defects. Males predominated for cleft lip; females for cleft palate. Cleft lip (alone) was more

common in babies born to women aged 35 years and over. Sudden declines in registered prevalence wereobserved in 1978 and 1985. Clefts were more common in socioeconomically deprived areas of the city. In

comparison with data from elsewhere, Glasgow seems to have a low rate of cleft lip, a high rate of cleftpalate, and a high rate of associated defects. Many of the findings of cleft palate in Glasgow could beexplained by the interaction of an unidentified environmental teratogen with a susceptible population.

15.Am J Epidemiol.2006 May 1;163(9):790-810. Epub 2006 Feb 22.Association between the transforming growth factor alpha gene and nonsyndromic oral clefts: a

HuGE review.

Vieira AR.


Department of Oral Medicine and Pathology, School of Dental Medicine, University of Pittsburgh, 3501Terrace Street, Pittsburgh, PA 15261, USA. [email protected]

Abstract
http://www.nlm.nih.gov/medlineplus/craniofacialabnormalities.htmlhttp://www.nlm.nih.gov/medlineplus/craniofacialabnormalities.htmlhttp://www.nlm.nih.gov/medlineplus/birthdefects.htmlhttp://www.nlm.nih.gov/medlineplus/birthdefects.htmlhttp://www.nlm.nih.gov/medlineplus/birthdefects.htmlhttp://www.nlm.nih.gov/medlineplus/cleftlipandpalate.htmlhttp://www.nlm.nih.gov/medlineplus/cleftlipandpalate.htmlhttp://www.nlm.nih.gov/medlineplus/cleftlipandpalate.htmlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/http://www.ncbi.nlm.nih.gov/pubmed/?term=Womersley%20J%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Womersley%20J%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Stone%20DH%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Stone%20DH%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Stone%20DH%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/citedby/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/citedby/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/citedby/http://www.ncbi.nlm.nih.gov/pubmed/16495466http://www.ncbi.nlm.nih.gov/pubmed/16495466http://www.ncbi.nlm.nih.gov/pubmed/16495466http://www.ncbi.nlm.nih.gov/pubmed?term=Vieira%20AR%5BAuthor%5D&cauthor=true&cauthor_uid=16495466http://www.ncbi.nlm.nih.gov/pubmed?term=Vieira%20AR%5BAuthor%5D&cauthor=true&cauthor_uid=16495466http://www.ncbi.nlm.nih.gov/pubmed/16495466http://www.ncbi.nlm.nih.gov/pubmed/16495466http://www.ncbi.nlm.nih.gov/pubmed/16495466http://www.ncbi.nlm.nih.gov/pubmed/16495466http://www.ncbi.nlm.nih.gov/pubmed?term=Vieira%20AR%5BAuthor%5D&cauthor=true&cauthor_uid=16495466http://www.ncbi.nlm.nih.gov/pubmed/16495466http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/citedby/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/http://www.ncbi.nlm.nih.gov/pubmed/?term=Stone%20DH%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Womersley%20J%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779220/http://www.nlm.nih.gov/medlineplus/cleftlipandpalate.htmlhttp://www.nlm.nih.gov/medlineplus/birthdefects.htmlhttp://www.nlm.nih.gov/medlineplus/craniofacialabnormalities.html


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Transforming growth factor alpha (TGFA) is a well-characterized mammalian growth factor. Since thefirst report of an association between DNA sequence variants at the TGFA genetic locus and

nonsyndromic oral clefts, 47 studies have been carried out, producing conflicting results. In this review,the author synthesizes findings from published reports on the association between the TGFA gene andclefting in humans. Bias, lack of statistical power, and genuine population diversity can explain thediverse results. In the aggregate, TGFA is probably a genetic modifier of clefting in humans, which is

consistent with the oligogenic model suggested for nonsyndromic oral clefts.

Genomics.1999 Nov 1;61(3):237-42.

Transforming growth factor-alpha (TGFA): genomic structure, boundary sequences, and mutation

analysis in nonsyndromic cleft lip/palate and cleft palate only.

Machida J,Yoshiura Ki,Funkhauser CD,Natsume N,Kawai T,Murray JC.


Department of Pediatrics, University of Iowa, Iowa City, Iowa, 52242, USA.

AbstractTransforming growth factor-alpha (TGFA) has been proposed as a candidate gene in the etiology of

nonsyndromic cleft lip with or without cleft palate (NS-CL/P) and of nonsyndromic cleft palate only (NS-CPO). Biologic support for a role of TGFA arises from its presence at high levels in the epithelial tissue

of the medial edge of the palatal shelves at the time of shelf fusion in mice. Genetic support for the role ofTGFA in clefting comes from the reported association of TGFA alleles with human NS-CPO and NS-CL/P. In this study we report the sequence and structure of human genomic TGFA and the search for

causal TGFA mutations in 250 individuals with NS-CL/P or NS-CPO by conformational analysis of thecoding sequence, splice junctions, and a portion of the 3' untranslated region strongly homologous

between human and mouse. We confirm that human TGFA is composed of six exons and here report

several new sequence substitutions and their frequencies. Five variants in conserved segments mayrepresent rare causes for clefting in humans and provide support for the role of TGFA in facial

morphogenesis.Copyright 1999 Academic Press.

16.Cleft Palate Craniofac J.1997 Jan;34(1):1-6.Studies of the candidate genes TGFB2, MSX1, TGFA, and TGFB3 in the etiology of cleft lip

and palate in the Philippines.

Lidral AC,Murray JC,Buetow KH,Basart AM,Schearer H,Shiang R,Naval A,Layda E,Magee

K,Magee W.

Sourcehttp://www.ncbi.nlm.nih.gov/pubmed/9003904

Department of Orthodontics, University of Iowa, Iowa City 52242-1083, USA.

Abstract

Population-based candidate-gene studies can be an effective strategy for identifying genes involved in the

etiology of disorders where family-based linkage studies are compromised by lack of access to affectedmembers, low penetrance, and/or genetic heterogeneity. We evaluated association data for four candidate

genes using a population from the Philippines that is genetically separate from previously studied

Caucasian populations. Case ascertainment was made possible by collaboration with Operation Smile, avolunteer medical organization, which facilitated identification of a large number of cases for study. Anew allelic variant of transforming growth factor-beta 3 was identified to use in these studies. Afterexclusion of syndromic cases of cleft lip and palate, no evidence for association with previously reported

allelic variants of transforming growth factor-beta 2 (TGFB2), homeobox 7 (MSX1), or transforminggrowth factor-alpha (TGFA), or with the new TGFB3 variant was detected. Previous association studiesusing Caucasian populations of nonsyndromic cleft lip and/or palate (CL/P) and cleft palate only (CPO)have strongly suggested a role for TGFA in the susceptibility of clefting in humans. Exclusion ofsignificant association in a non-Caucasian population for TGFA suggests that TGFA plays less of a role
http://www.ncbi.nlm.nih.gov/pubmed/10552925http://www.ncbi.nlm.nih.gov/pubmed/10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Machida%20J%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Machida%20J%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Yoshiura%20Ki%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Yoshiura%20Ki%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Yoshiura%20Ki%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Funkhauser%20CD%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Funkhauser%20CD%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Funkhauser%20CD%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Natsume%20N%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Natsume%20N%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Natsume%20N%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Kawai%20T%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Kawai%20T%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Kawai%20T%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Murray%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Murray%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Murray%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed/10552925http://www.ncbi.nlm.nih.gov/pubmed/10552925http://www.ncbi.nlm.nih.gov/pubmed/10552925http://www.ncbi.nlm.nih.gov/pubmed/9003904http://www.ncbi.nlm.nih.gov/pubmed/9003904http://www.ncbi.nlm.nih.gov/pubmed/9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Lidral%20AC%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Lidral%20AC%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Murray%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Murray%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Murray%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Buetow%20KH%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Buetow%20KH%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Buetow%20KH%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Basart%20AM%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Basart%20AM%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Basart%20AM%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Schearer%20H%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Schearer%20H%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Schearer%20H%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Shiang%20R%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Shiang%20R%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Shiang%20R%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Naval%20A%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Naval%20A%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Naval%20A%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Layda%20E%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Layda%20E%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Layda%20E%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20K%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20K%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20K%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20K%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20W%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20W%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20W%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed/9003904http://www.ncbi.nlm.nih.gov/pubmed/9003904http://www.ncbi.nlm.nih.gov/pubmed/9003904http://www.ncbi.nlm.nih.gov/pubmed/9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20W%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20K%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Magee%20K%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Layda%20E%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Naval%20A%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Shiang%20R%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Schearer%20H%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Basart%20AM%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Buetow%20KH%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Murray%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed?term=Lidral%20AC%5BAuthor%5D&cauthor=true&cauthor_uid=9003904http://www.ncbi.nlm.nih.gov/pubmed/9003904http://www.ncbi.nlm.nih.gov/pubmed/10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Murray%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Kawai%20T%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Natsume%20N%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Funkhauser%20CD%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Yoshiura%20Ki%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed?term=Machida%20J%5BAuthor%5D&cauthor=true&cauthor_uid=10552925http://www.ncbi.nlm.nih.gov/pubmed/10552925


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than it does in Caucasians. This may be due to multiple or different genetic and/or environmental factorscontributing to the etiology of this most common c

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