GEPY 6911: Functional Implications of

Visual ImpairmentSession 8: Wednesday October 28, 2015:

Syndromes and Associated Eye Conditions

Questions from last week?

CVI Assignment

Final Project/Presentation

Syndromes and Associated Eye Conditions

Agenda

There are a number of syndromes with systemic manifestations that have ophthalmic implications

Patients with these syndromes are seen in ophthalmology clinics to asses and treat their ocular symptoms

Students with these syndromes may be referred to you!

Introduction

They can be classified according to the types of disorders they cause:◦ Chromosomal◦ Skeletal◦ Developmental◦ Connective Tissue◦ Hearing

They can also be classified according to how they cause their effect:◦ Physcial/Chemical injuries◦ Neural tube defects

Classification

Chromosomal Disorders

Trisomy 21Turner Syndrome

Etiology◦ Extra copy of chromosome 21◦ Most common single cause of human birth defects

Systemic Signs and Symptoms◦ Short stature◦ Developmental delay◦ Flattened facial appearance

Depressed nasal bridge◦ Congenital Heart defects◦ Prevalence of diseases such as leukemia,

hypothyroidism and diabetes mellitus

Trisomy 21 (Down Syndrome)

Ophthalmic Signs and Symptoms◦ Upward slant of palpebral fissures◦ Strabismus◦ Nystagmus◦ Keratoconus◦ Cataracts◦ Myopic refractive errors

Treatment◦ Require multi-systemic evaluations◦ Correcting refractive error, removing cataracts, etc.

Trisomy 21 (Down Syndrome)

Prognosis◦ Serious heart problems and higher risk of

leukemia may lead to early death◦ Adults with DS have an increased risk of dementia

◦ Generally they are living longer than ever!

Trisomy 21 (Down Syndrome)

Etiology◦ Absence of a set of genes on the X chromosome of

affected females

Systemic Signs and Symptoms◦ Short stature◦ Prone to osteoporosis and renal problems◦ Webbed, wide neck and low hairline◦ Scoliosis◦ Hypertension◦ Hyperthyroidism◦ Infertility◦ Swollen hands and feet

Turner Syndrome

Ophthalmic Signs and Symptoms◦ Ptosis◦ Strabismus◦ Amblyopia◦ Cataracts◦ Red-green color blindness◦ Dry eyes

Treatment◦ Monitoring of heart defects◦ Calcium and Vit. D to prevent osteoporosis◦ Cataract surgery ◦ Treatments for dry eyes

Turner Syndrome

Prognosis◦ Can have a normal life ◦ Require careful monitoring by a doctor

Turner Syndrome

Skeletal DisordersCrouzon/Apert SyndromeTreacher-Collins SyndromeGoldenhar SyndromePierre-Robin SyndromeMarfan SyndromeStickler SyndromeCockayne Syndrome

Etiology◦ Caused by premature fusion of the cranial sutures

causing a skull deformity◦ Sporadic mutations◦ Autosomal dominant

Systemic Signs and Symptoms◦ Cranium is egg-shaped ◦ Crowding of the teeth◦ Syndactyly of the fingers and toes (Apert)◦ Heart and Kidney malformations (Apert)◦ Short stature◦ Hearing impairments

Crouzon/Apert Syndrome

Ophthalmic Signs and Symptoms◦ Proptosis (caused by abnormal orbital structure)◦ Optic nerve compression◦ Strabismus◦ Hyperopic refractive errors◦ Iris colobomas◦ Nystagmus◦ Ptosis◦ Retinal detachments◦ Congenital cataracts

Crouzon/Apert Syndrome

Treatment◦ No treatments exist

Cosmetic surgeries

Prognosis◦ Generally good◦ Can sometimes have high intracranial pressure

which can cause death

Crouzon/Apert Syndrome

Etiology◦ Caused by a defective protein◦ Is hereditary◦ Possible mutation on chromosome 5

Systemic Signs and Symptoms◦ Small chin◦ Steep angle of the lower jaw (breathing problems)◦ Prominent nose◦ Underdeveloped ears◦ Hearing loss ◦ Heart defects

Treacher-Collins Syndrome

Ophthalmic Signs and Symptoms◦ Strabismus◦ Downward slant of the eyes◦ Absence of lashes on the lower lid margin◦ Sometimes coloboma

Treatments◦ Genetic counselling◦ Monitoring heart defects◦ Cosmetic surgery

Treacher-Collins Syndrome

Prognosis◦ Normal intelligence and life span◦ Must be followed for any systemic complications

Treacher-Collins Syndrome

Etiology◦ Unknown◦ Sporadic occurrence, AD and AR inheritance

Systemic Signs and Symptoms◦ Facial asymmetry due to abnormal development of

the underlying facial bones◦ Growths of skin and cartilage around the ear◦ Hearing loss is common◦ Cleft lip/palate◦ Malformations of the spine and skull◦ Sometimes developmental delay

Goldenhar Syndrome

Ophthalmic Signs and Symptoms◦ Overgrowth of normal tissues on the outer coats

of the eye◦ Dermoids◦ Upper lid colobomas◦ Ptosis◦ Narrowing of the palpebral fissures◦ Lacrimal system problems◦ Retinal and optic nerve problems◦ Strabisums

Goldenhar Syndrome

Treatment◦ Surgery can be done on the bones of the face◦ Repair of ptosis, strabismus surgery, removal of

larger dermoids

Prognosis◦ Dependent on associated complications

Goldenhar Syndrome

Etiology◦ Unknown◦ AR inheritance

Systemic Signs and Symptoms◦ Cardiovascular problems◦ Hyperextendible joints◦ Small mandible◦ Foot and hip abnormalities◦ Scoliosis◦ CNS problems (50% of cases)

Language delay, epilepsy and hydrocephalus

Pierre-Robin Syndrome

Ophthalmic Signs and Symptoms◦ Congential glaucoma◦ High myopia◦ Retinal detachment◦ Congenital cataracts◦ Microphthalmos◦ Esotropia

Pierre-Robin Syndrome

Treatment◦ Treatment of systemic complications

Respiratory/feeding problems Airway obstruction

◦ Treatment of glaucoma, cataracts, strabismus as needed

Prognosis◦ Depends on complications◦ Mortality rates of up to 30% due to airway

obstruction and feeding difficulties

Pierre-Robin Syndrome

Etiology◦ AD disorder◦ Mutation on chromosome 15

Systemic signs and symptoms◦ Long fingers and toes◦ Taller for age◦ Dislocations of hips and mandible◦ Cardiovascular defects

Marfan Syndrome

Ophthalmic Signs and Symptoms◦ Lens dislocation◦ Large, flat corneas◦ Myopia◦ Cataract◦ Miosis◦ Glaucoma◦ Retinal detachment◦ Ptosis◦ Strabismus◦ Incomplete choroidal formation

Marfan Syndrome

Treatment◦ Treatment of systemic complications

Hormone therapy Heart surgery

◦ Correction of refractive errors and treatment of associated eye findings

Prognosis◦ Depends on severity of cardiovascular problems

Marfan Syndrome

Etiology◦ AD inheritance◦ Mutation on chromosome 12

Systemic Signs and Symptoms◦ Flattened face◦ Depressed nasal bridge◦ Short nose◦ Deafness◦ Dental abnormalities◦ Cleft palate◦ Scoliosis◦ Short sature◦ Arthritis

Stickler Syndrome

Ophthalmic Signs and Symptoms◦ Myopia (8-18 diopters)◦ Retinal detachments◦ 75% can develop myopia before 20 years of age◦ Cataracts◦ Less frequently

Lens dislocation Glaucoma

Stickler Syndrome

Treatment◦ Hip replacement◦ Hearing aids◦ Correction of myopia◦ Retinal detachment surgery

Treatment◦ Good prognosis◦ Vision loss is most severe complication◦ Arthritis can decrease quality of life in older

patients

Stickler Syndrome

Etiology◦ Defect in a DNA repair mechanism◦ AR inheritance

Systemic Signs and Symptoms◦ Progressive degeneration of CNS and PNS◦ Dwarfism apparent by one year of age◦ Microcephaly ◦ Developmental delay◦ Hearing loss◦ Thin, dry hair◦ Narrow nose◦ Sunken eyes◦ Dental abnormalities◦ Photosensitive skin

Cockayne Syndrome

Ophthalmic Signs and Symptoms◦ Salt-and-pepper retinal pigmentation◦ Optic atrophy◦ Corneal opacity◦ Cataracts◦ Hyperopia◦ Strabismus◦ Nystagmus◦ Decreased lacrimation◦ Photophobia

Cockayne Syndrome

Treatment◦ Specific to specific complications

See audiologist for hearing problems Ophthalmologist for eye problems Dentists for dental abnormalities

Prognosis◦ Not good◦ Death usually occurs in adolescence or early

adulthood

Cockayne Syndrome

Developmental Disorders

Bardet-BiedlPrader-Willi SyndromeSepto-Optic DysplasiaCHARGE SyndromeAlstrom

Etiology◦ Unknown◦ AR inheritance

Systemic Signs and Symptoms◦ Obesity◦ Developmental delay◦ Kidney abnormalities◦ Can sometimes have extra fingers/toes or fusion of

fingers/toes◦ Speech difficulties◦ Diabetes mellitus

Bardet-Biedl

Ophthalmic Signs and Symptoms◦ RP or progressive pigmentary retinal degeneration

or rod-cone dystrophy◦ Nystagmus sometimes present

Treatment◦ No specific treatments◦ Manage vision loss◦ Obesity is resistant to treatment

Bardet-Biedl

Etiology◦ Missing gene on chromosome 15◦ Missing genetic material on the father’s part of the chromosome

Systemic Signs and Symptoms◦ Feeding difficulties in infants resulting in low weight until 6

months of age◦ Obesity occurs around age 2◦ Extreme insatiable appetite ◦ Heart problems◦ Diabetes mellitus◦ Developmental delay◦ Short stature◦ Small hands and feet◦ Cutaneous hypopigmentation

Prader-Willi Syndrome

Ophthalmic Signs and Symptoms◦ Non-accommodative or infantile-type strabismus◦ Most have blue irides◦ Iris transillumination defects◦ Nystagmus (esp. on lateral gaze)◦ Myopia in ¼ of cases◦ RPE hypopigmentation◦ Foveal hypoplasia

Treatment◦ Must be followed by multiple specialists◦ Monitor their diet and be physically active

Prader-Willi Syndrome

Prognosis◦ Generally good◦ Normal life span◦ Complications, like obesity can shorten life

expectancy and quality of life

Prader-Willi Syndrome

Etiology◦ Defect of normal embryological development◦ Has been linked to young maternal age and in-utero

cocaine exposure◦ Rare familiar occurance

Systemic Signs and Symptoms◦ Pituitary deficiency (variable degrees)◦ Sometimes seizures◦ Low muscle tone◦ Jaundice at birth◦ Developmental delay

Septo-Optic Dysplasia/de Morsier Syndrome

Ophthalmic Signs and Symptoms◦ Optic nerve hypoplasia◦ Nystagmus◦ Strabismus◦ Variable degrees of visual impairment

Treatment◦ Hormone replacement therapy for hormone deficiencies◦ No treatment for ophthalmic symptoms

Prognosis Dependent on the presence and severity of symptoms

Septo-Optic Dysplasia/de Morsier Syndrome

Etiology◦ AD genetic disorder

Systemic Signs and Symptoms◦ Choanal atresia – back of the nasal sinuses on one or both

sides is narrowed or doesn’t connect with the back of the throat

◦ Cranial nerve abnormality – difficulty swallowing, facial paralysis

◦ Heart defect◦ Growth retardation◦ Developmental delay◦ Underdeveloped genitals◦ Ear abnormalities

CHARGE Syndrome

Ophthalmic Signs and Symptoms◦ Coloboma◦ Micorophthalmos or anophthalmos

Treatment◦ Treatment of many medical and physical problems

Prognosis◦ Can have many life-threatening issues◦ With advances in medical care, these children can

survive and become healthy individuals

CHARGE

CHARGE

CHARGE

Etiology◦ Caused by a defective gene, but it’s unknown how this gene

causes the disorder◦ AR inheritance

Systemic Signs and Symptoms◦ Dark patches of skin◦ Deafness◦ Impaired heart function◦ Obesity◦ Progressive kidney failure◦ Slowed growth◦ Symptoms of type II diabetes◦ Hypothyroidism◦ Developmental delay

Alstrom

Ophthalmic Signs and Symptoms◦ Cone-rod dystrophy◦ Light sensitivity

Treatment◦ No specific treatment◦ Treatment for different symptoms

Diabetes medication Hearing aids Heart medication Thyroid hormone replacement

◦ Prognosis Good Dependent on associated symptoms

Alstom

Connective Tissue Disorders

Ehlers-Danlos Syndrome

Etiology◦ Genetic defect in collagen and connective tissue synthesis and

structure◦ Can be AR, AD or X-linked recessive

Systemic Signs and Symptoms◦ Stretchable skin◦ Underlying vessels are diseased and visible through the skin◦ Fragile skin◦ Poor wound healing◦ Increased joint flexibility ◦ Scoliosis◦ Respiratory defects◦ Cardiac problems◦ Low weight◦ Short stature

Ehlers-Danlos Syndrome

Ophthalmic Signs and Symptoms◦ Found in Type VI ED Syndrome◦ Retinal detachment◦ Retinal hemorrhage ◦ Glaucoma◦ Abnormal coloration of the sclera◦ In rare cases the globe can rupture◦ Myopia◦ Keratoconus

Ehlers-Danlos Syndrome

Treatment◦ No specific treatment exists◦ Consult ophthalmologist and genetic counsellor◦ Refrain from heavy lifting, contact sports or

anything that puts stress on joints

Prognosis◦ Normal ◦ In Type IV, life expectancy is to about 50 years of

age

Ehlers-Danlos Syndrome

Physical/Chemical Injury

Fetal Alcohol Syndrome

Etiology◦ Women who drink heavily during their pregnancy

will produce a child with the features of FAS

Fetal Alcohol Syndrome

Systemic Signs and Symptoms◦ Craniofacial abnormalities

Mid-face hypoplasia Low nasal bridge Thin upper lip Cleft palate Flat philtrum

◦ CNS and neurobehavioral anomalies Microcephaly Developmental delay Siezures ADHD

◦ Cardiovascular disorders◦ Hearing loss

Fetal Alcohol Syndrome

Ophthalmic Signs and Symptoms◦ Short palpebral fissure◦ Monocular or asymmetric ptosis◦ Myopia is common◦ Strabismus (usually ET)◦ Optic nerve hypoplasia

Treatment◦ Treatment of associated birth defects ◦ Medications to treat ADHD

Fetal Alcohol Syndrome

Prognosis◦ Normal life span◦ Quality of life can be impaired

Mental health problems later in life Drug and alcohol addictions later in life

Fetal Alcohol Syndrome

Neural Tube DefectsSpina Bifida

Etiology◦ Occurs when a growing fetus is not exposed to

enough folic acid between the 17th and 30th day of gestation.

◦ The neural tube does not close completely or at all, which causes an incomplete closure of the spinal column

Spina Bifida

Systemic Signs and Symptoms◦ Hydrocephalus◦ Spinal cord is not protected by the spinal column

causing the spinal cord to grow into a growth in the back

◦ Partial paralysis◦ Bladder/bowel control problems◦ Learning disabilities

Spina Bifida

Ophthalmic Signs and Symptoms◦ Microphthalmus or anophthalmos◦ Choriodial coloboma◦ Atrophy of retinal ganglion cells and macula◦ Optic atrophy◦ Strabismus

Treatments◦ Can be treated in-utero if detected early enough◦ Shunts for hydrocephalus◦ Continuous follow-up from a variety of specialists

Spina Bifida

Prognosis◦ Longer life span now with advances in treatment◦ Shunting of hydrocephalus can lead to near-

normal intelligence

Spina Bifida

Hearing DisordersUsher Syndrome

Etiology◦ Unknown◦ AR inheritance

Systemic Signs and Symptoms◦ Sensorineural hearing loss

Progressive◦ Developmental delay◦ Cerebral atrophy

Usher Syndrome

Ophthalmic Signs and Symptoms◦ Night blindness

Peaks at 5 years and again between 15-20 years◦ Retinitis Pigmentosa◦ Progressive vision loss ◦ VF become constricted◦ Bull’s-eye maculopathy◦ Cataract◦ Vitreous detachment

Usher Syndrome

Treatment◦ No cure◦ Treatment of different complications◦ Early detection is important

Prognosis◦ Visual and auditory prognosis will vary depending

on severity◦ No reports on changes in lifespan

Usher Syndrome

There are a number of Syndromes that have associated eye conditions

Think about all of the different functional implications you’ve learned and how they would apply to each case

Conclusion

Happy Halloween!!!Next class: Optics and Low Vision Devices

Quiz for tonight’s lecture is due by November 8, 2015