Archives of Disease in Childhood 1994; 71: 44-49

The swollen leg and primary lymphoedema

N B Wright, H M L Carty

AbstractChildren who present with unilateral orbilateral swelling of the legs are oftensuspected ofhaving a deep venous throm-bosis. The incidence of deep venousthrombosis in children is low and lym-phoedema may be a more appropriatediagnosis. Lymphoedema can be primaryor secondary. In childhood, primarylymphoedema is more common and maybe seen associated with other congenitalabnormalities, such as cardiac anomaliesor gonadal dysgenesis. Primary hypo-plastic lymphoedema is the most oftenencountered type. It is more common ingirls, especially around puberty, and istypically painless. Atypical presentationsproduce diagnostic confusion and mayrequire imaging to confirm the presence,extent, and precise anatomical nature ofthe lymphatic dysplasia. This articledescribes four patients presenting withlimb pain and reviews the clinical featuresand imaging options in children withsuspected lymphoedema.(Arch Dis Child 1994; 71: 44-49)

A child with a swollen leg may present adifficult diagnostic problem. The initial clinicaldiagnosis is usually a deep venous thrombosis,although these are uncommon in children. Ifpelvic and vascular ultrasound, includingcolour flow and Doppler imaging, does notshow venous thrombus or its cause, thena large number of other disorders need tobe considered. These include lymphoedema,lipoedema, hemihypertrophy, neurofibro-matosis, macrodystrophia lipomatosa, reflexsympathetic dystrophy, multiple enchondro-matosis, and the mixed vascular deformities(for example, Klippel-Trenaunay syndrome,congenital arteriovenous fistulas, and diffusehaemolymphangiomatosis). Although mostof these uncommon disorders are clinicallydistinguishable, there will be a small propor-tion of patients in whom the diagnosis remainsobscure. Such a group includes those childrenwith primary lymphoedema. This paper dis-cusses the clinical and radiological features ofprimary lymphoedema and presents four casereports.

of her right hand, but this was normal atpresentation. The swelling of her ankleswas associated with pain and limitation ofmovement. Menarche occurred at 11 years ofage. On clinical examination she had bilateralpitting oedema of the legs, more markedon the right, and confined to below bothknees. Haemoglobin, white cell count, plateletcount, erythrocyte sedimentation rate, bloodbiochemistry, rheumatoid factor, and thyroidfunction tests were all normal. Plain radio-graphy and an isotope bone scan gave normalresults. The child was referred for rheumato-logical and dermatological opinions. A firmdiagnosis was not made and advice was soughtfrom a paediatrician. Further investigation wasdiscussed with the radiology department and alymphangiogram was suggested. A bilaterallymphangiogram showed a solitary, mildlyectatic lymphatic vessel on the left leg withnormal inguinal, pelvic, and lumbar lymphnodes (fig 1). On the right there was aplasia ofthe lymphatic vessels with dermal backflow oninjection of Patent Blue dye.

CASE 2A 14 year old previously healthy girl presentedwith a 12 month history of intermittent bilat-eral leg pain. The pain was initially localisedaround the knees but later affected the thighsand hips. It was occasionally severe enough to

Department ofRadiology, RoyalLiverpool Children'sNHS Trust, Alder Hey,Eaton Road, LiverpoolL12 2APN B WrightH M L Carty

Correspondence to:Dr Carty.Accepted 23 March 1994

Case reportsCASE 1A 13 year old previously healthy girl presentedto an orthopaedic clinic with an 11 monthhistory of intermittent swelling of her ankles.She recalled a trivial injury to the back ofher right calf before the onset of symptoms.She had also noticed mild intermittent swelling

Figure 1 Lymphangiogram showing a solitary, mildlyectatic lymphatic vessel in the thigh.

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Figure 2 Bilateral lymphangiogram showingmorphological hypoplasia and a paucity of valves in thelymphatic vessels of the calf.

wake her at night. Shortly after the onset ofsymptoms, swelling of the legs developed.Clinical examination showed bilateral swellingof the legs with pitting oedema of both anklesand the presence of striae over the thighs andbuttocks. She was normotensive. A number ofclinical diagnoses were considered, includingCushing's disease and intra-abdominal patho-logy. Routine blood tests were normal, as werecortisol concentrations. A lateral skull radio-graph and estimation ofbone age were normal.Pelvic ultrasound and abdominal computedtomography were normal. A bilateral lymph-angiogram showed morphological hypoplasia

Figure 3 Lymphangiogram showing a solitary iliaclymphatic vessel and mildly hypoplastic lymph nodes. Thethigh lymphatic vessels are normal in size but the valves areabnormal.

with a paucity of valves, but normal nodalmorphology (fig 2). Features were consistentwith a primary lymphatic dysplasia.

CASE 3A 13 year old previously healthy girl presentedwith a three day history of unilateral calfswelling and itching around the ankle and foot.Clinical examination confirmed the presenceof mildly tender pitting oedema from the kneeto the ankle. Otherwise, the clinical examina-tion was normal. A tentative diagnosis of deepvenous thrombosis was made. Her haemo-globin, white cell count and differential,platelet, erythrocyte sedimentation rate, bloodbiochemistry, urine analysis, and clottingprofile were all normal. Vascular Dopplerultrasound was performed and was normal.The swelling resolved within 72 hours withelevation and, although pain and tendernesspersisted, the child was allowed homewhile receiving a short course of ibuprofen(200 mg four times a day). Approximatelythree weeks later she returned with recurrentsymptoms. Her foot was also noted to becooler, but peripheral pulses were normal.Plain radiography of the leg and ultrasound ofthe pelvis were normal. Further investigationwas discussed with the radiology department.Ultrasound of the affected leg confirmedgeneralised thickening of the subcutaneoustissues distally. A lymphangiogram wasperformed on the affected leg. This showedfine calf lymphatic vessels and a solitaryiliac lymphatic vessel. The lymph nodesappeared hypoplastic. The diagnosis ofprimary hypoplasia of the lymphatic systemwas made (fig 3).

CASE 4A 16 year old previously healthy girl presentedwith an acutely swollen right hand and arm. Avenous thrombosis was suspected and veno-graphy was performed on the arm. This wasnormal. Plain radiography showed no abnor-mality. Computed tomography showed anincrease in the thickness of the subcutaneouslayers of the arm, but no obvious cause for theswelling. Lymphoedema was suspected andlymphatic obstruction confirmed by lympho-scintigraphy, no obvious lymphatic vesselsbeing identified. The arm swelling resolvedspontaneously, but, a few months later,moderately painful leg swelling occurred.Atypical lymphoedema was suspected anda lymphangiogram was performed. Thisconfirmed a lymphatic dysplasia of the legs.

DiscussionLymphoedema has been described as 'aswelling of some part of the body due to a faultin the lymphatic system'.1 The pathologicalcharacteristics include excess tissue proteinand oedema, which are initially reversible,but eventually chronic inflammation andfibrosis occur.2 This is reflected clinically byswelling which pits on pressure, but with time

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Genetic syndromes associated with lymphoedema

Turner's syndrome'0Noonan's syndrome"Pes cavus'2Distichiasis (double row eyelashes) 13 14Yellow nail syndrome'5 16Ptosis'7Hypoparathyroidism'8Microcephaly19-21Arteriovenous malformations22Neuronal migration defects23Facial anomalies24 25Cholestasis26

becomes thickened and unyielding. Super-vening inflammation accelerates the processand hyperkeratosis, verrucas, and condylomataformation may occur. Ulceration is rare.Further complications of chronicity includeelephantiasis, lymphocutaneous fistulas, andrarely the development of angiosarcoma.3-7

CLASSIFICATIONLymphoedema can be a primary or, morecommonly, a secondary disorder. Primarylymphoedema is more often seen in childrenthan in adults. The secondary causes are clearlydefined by aetiology. They include those seen ingeneralised oedema (for example, cardiac,renal, and hepatic failure, and hypo-proteinaemia) and those due to local causessuch as trauma (including surgery), malignancy,infection (for example, filarial), inflammation(for example, chronic eczema), and radiation.

Primary lymphoedema is classified by age atpresentation: congenita, praecox (age 1 to 35years old), and tarda (over 35 years). Someconfusion may arise in that lymphoedemapraecox and tarda, though presenting inlater life, are due to an underlying congenitalanomaly. The suffix merely describes the age atpresentation. An alternative classification usesradiological appearances: aplasia, hypoplasia,and hyperplasia. There is a large, but compara-tively rare, heterogeneous group of primarylymphoedemas which are hereditary (Milroy'sand Meige's disease8 9) or associated withgenetic syndromes. The table above sum-marises the latter; most show features whichshould not cause diagnostic problems. Anincreased incidence of lymphoedema is alsoseen in congenital heart disease27 and themixed vascular deformities.2829 Primarylymphoedema has also been considered as oneend of a spectrum of disorders of the lymphaticsystem encompassing lymphangiectasia,lymphangiomas, and chylous effusions.30 Theincidence of other congenital malformationsseen in children with primary lymphoedema isreported by some workers to be high,' 31 32although this is contentious.33

CLINICAL ASPECTS OF PRIMARY LYMPHOEDEMA

Classical primary lymphoedema is a mild,painless swelling of the distal extremity whichprogresses relentlessly to a huge, swollen limb.The diagnosis of primary lymphoedema ismade by taking a careful history and perform-ing a thorough examination. There may beobvious features, such as those of Turner's

syndrome, which help in confirming thediagnosis. The clinical diagnosis in the fourcases presented here was made difficult by thepresence of a painful limb, which undoubtedlycaused some confusion.Lymphoedema praecox is the most common

type of primary lymphoedema and both thecongenita and the praecox types are morecommon in females (2:1 and 4:1 respectively).The sex difference is especially notable inthe second decade, possibly due to the onsetof puberty with consequent alterations inpelvic lymph flow and the effects of hormonalchanges. This theory is supported by childrenwith Turner's syndrome who develop lym-phoedema of the congenita type which oftenspontaneously resolves, only to recur oncemenarche is induced.'0 Oestrogen has beenspecifically implicated and subcutaneous tissuepressure is also thought to play a part, it beingslightly higher in boys than girls.33 Featuresoften arise spontaneously or are related to aminor insult such as in case 1.Some distinct clinicoradiological groups of

patients with primary lymphoedema have beendescribed.1 These include patients withprimary hypoplastic lymphoedema, unilateralmegalymphatics, and bilateral hyperplasia ofthe lymphatics.

Primary hypoplastic lymphoedemaThis group forms about 80% of patientswith primary lymphoedema of the legs. It isalso the group of patients causing the greatestdiagnostic confusion. The comments madeabout lymphoedema praecox refer mainly tothis group. There is a spectrum of disease withtwo extremes defined by lymphographic,genetic, and histopathological features. At oneend of the spectrum are patients with hypo-plasia of the proximal lymphatics and distaldistension. There is usually a more acutehistory of unilateral severe swelling, an equalsex distribution, and extensive lymph nodefibrosis. At the opposite end is distal lymphatichypoplasia, which is more common in females,milder in nature, symmetrical, and confined tobelow the knee. There may be a family historyand the lymph nodes are normal.34 35 Manypatients have features between these twoextremes, as do all four cases presented here.

Unilateral megalymphaticsIn this group, patients almost always havea capillary angioma on the affected limb ortrunk. Bilateral features are rare, there isno family history, and there is an even sexdistribution.

Bilateral hyperplasiaThis predominantly male group of patientsshows bilateral symmetrical lymphoedemamainly affecting the legs below the knees.Some also have symmetrical angiomataaround their feet. A family history is commonand a number of other deformities may bepresent, the most common being distichiasis36

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and cardiac anomalies.27 The thoracic ductis often absent or abnormal, reflectingthe intimate relation between cardiac andlymphatic development.Two other distinct groups were described

by Kinmonth,l Milroy's disease and lympho-edema associated with gonadal dysgenesis orpes cavus. In the two groups the lymphaticsshow hypoplasia or aplasia. Nodal fibrosissimilar to that seen in primary hypoplasticlymphoedema is seen in Milroy's disease.

IMAGINGThe investigation of a child with a swollenleg must include the initial exclusion ofsystemic and vascular causes. The latter isrelatively easy and should include vascularDoppler ultrasound in the first instance.The exclusion of systemic causes andsecondary lymphoedema may involve a widerange of investigations, and, from the imagingaspect, pelvic ultrasound is probably thesimplest, non-invasive next step, and canbe combined with the vascular study.Subsequently, imaging should be guidedby the clinical course and the results ofother investigations. Once primary lym-phoedema is suspected, imaging should aimto confirm the diagnosis, define its extentand severity, and detect any possible compli-cations. Consideration must be given tothe necessity of further investigation. It isof limited value in confirming the presenceof a lymphatic problem in a child witha disease known to be associated with lym-phatic abnormality, such as Turner'ssyndrome, and we would confine furtherinvestigation to those patients in whomthere is diagnostic confusion. Therefore,most of our remarks refer to primaryhypoplastic lymphoedema, usually presentingas lymphoedema praecox.

Plain radiographs are primarily performed toexclude underlying soft tissue or bony path-ology. Radiographs may show a generalincrease in the depth of the fat planes, butunless particularly marked, these may onlybe identified in retrospect and are of littlediscriminatory value.

Ultrasound examination is mandatory andshould be performed to exclude an underlyingvascular abnormality. It may also detect theincreased thickness of the subcutaneous andsubfascial compartments, especially when thedisorder is unilateral, and has been used forvolumetric assessment.37

LymphographyThere are two types of radiographic lympho-graphy: intralymphatic and interstitial.

Intralymphatic lymphography is the tradi-tional method and involves the cannulation of alymphatic vessel. It is technically demandingand is described in detail by Kinmonth.1The lymphatic vessels are initially visualisedafter a dermal injection of Patent Blue dye intoan interdigital webspace. Lymphatic obstruc-tion may be suspected at this stage if the

dye forms a large, but finely reticulated,network on the skin (dermal backflow).Several lymphographic patterns have beendescribed. In primary hypoplastic lympho-edema, the two extremes of the disease spec-trum show distinctive appearances. In the distalhypoplasia group there is a reduction in thenumber and calibre of the lymphatic vessels. Inproximal hypoplasia, the trunk lymphatics areabnormal and hypoplastic, with a distendedlymphatic tree distally. In unilateral mega-lymphatics, the affected limb has large andvalveless lymphatic vessels, and the lymphnodes are small, multiple, and scattered.The thoracic duct is large and incompetent. Inbilateral hyperplasia, there is both numericaland morphological hyperplasia of the vesselsand lymph nodes with an absent or partiallyatretic thoracic duct.

Interstitial lymphangiography is a relativelynew technique which allows the visualisationof the peripheral lymphatic vessels.38 39The technique is easier to perform thanintralymphatic lymphography and it hasbeen advocated as the study of choice forassessing lymphatic vascular morphology.40 Itdoes not show nodal morphology adequately,however, and this may be important inassessing prognosis.

Other imaging modalitesRadioisotopes (lymphoscintigraphy) can beused to evaluate lymphatic morphology andfunction.41-47 Several agents have been used,including technetium-99m labelled antimonysulphide colloid, dextran, and human serumalbumin. The radiolabelled isotope is injectedinto the subcutaneous interdigital space andimages obtained using a gamma camera.Static and dynamic images can be obtained.Lymph vessels and nodes, collateral circula-tion, dermal backflow, and vessel dilatationcan be recognised by lymphoscintigraphy, butit lacks precise anatomical definition.Quantitative (dynamic) assessment allows thedetection and grading of lymphoedema, and isa sensitive method of assessing mild and/orincipient lymphoedema.41

Both computed tomography and magneticresonance imaging (MRI) are better known fortheir ability to show lymphatic nodal morpho-logy. They can also differentiate lymphoedemafrom lipoedema and phleboedema.48-50Lymphoedema shows a typical honeycombpattern in both modalities between the muscleand subcutis. A pronounced increase in signalintensity is seen on T2 weighted images usingMRI. Failure to demonstrate the honeycombpattern does not exclude lymphoedema,however. Angiosarcomatous change can alsobe detected.5'

PROGNOSIS AND MANAGEMENTThe prognosis of primary hypoplastic lym-phoedema of the legs is variable. Relentlessprogression of the lymphoedema may notoccur and about 60% of patients reacha plateau of clinical severity after several

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years.33 52 It is therefore essential that asufficiently long period of conservativemanagement is undertaken to allow thedisorder to stabilise before contemplating anoperation. There are some clinical featureswhich may be helpful in predicting outcome.The prognosis is better for females, even ifthere is bilateral disease. The outcome isgenerally worse with an acute onset of oedemaand if swelling begins in the thigh. Maleswith unilateral oedema tend to progress tosevere change. The extent and degree oflymphatic abnormality in the vessels andnodes seen on lymphography will help topredict the outcome. Quantitative lympho-scintigraphy can also be helpful in gradingdisease severity and assessing treatmentsuccess.41The conservative management of lym-

phoedema includes exercise, self massage,elevation, compression (such as elasticatedstockings or pneumatic machine), and scrupu-lous attention to skin care. Medical treatmentwith diuretics has shown disappointingresults,33 and they are not recommendedfor long term treatment.2 Treatment withbenzopyrones has been shown to reduce excessprotein in the tissues with some beneficialeffects.53 It is also important not to under-estimate the psychological effects of thedisorder, especially in adolescence.An operation should be a last resort when

all conservative measures have failed. More-over, an operation early in the disease isinadvisable because of its varied nature. Thereare numerous potential surgical procedures,such as excisional operations, buried dermalflaps, and attempts at creating lymphati-covenous anastomoses, but complications arecommon and there is generally only a 30%success rate.33

Dr N B Wright, research fellow in paediatric radiology, is partlyfunded by a grant from E Merck ILimited and I G E MedicalSystems Limited.

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2 Casley-Smith JR, Foldi M, Ryan TJ, et al. Lymphedema:summary of the 10th International Congress ofLymphology: working group discussions and recommen-dations, Adelaide, Australia, August 10-17, 1985.Lymnphology 1985; 18: 175-80.

3 Schirger A, Harrison EG, Janes JM. Idiopathic lym-phedema.JAMA 1962; 182: 124-32.

4 Danese CA, Grishman E, Oh C, Dreiling DA. Malignantvascular tumours of the lymphedematous extremity. AnnSurg 1967; 166: 245-53.

5 Sordillo PP, Chapman R, Hajdu SI, Magill GB, Golbey RB.Lymphangiosarcoma. Cancer 1981; 48: 1674-9.

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7 Gajraj H, Barker SG, Burnand KG, Browse NL.Lymphangoisarcoma complicating chronic primarylymphoedema. BrjtSurg 1987; 74: 1180.

8 Milroy WF. Chronic hereditary edema: Milroy's disease.JAAMA 1928; 91: 1172-5.

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10 Hall JG, Gilchrist DM. Turner syndrome and its variants.Pediatr Clin North Amn 1990; 37: 1421 -40.

11 Lanning P, Simila S, Suramo I, Paavilainen T. Lymphaticabnormalities in Noonan's syndrome. Pediatr Radial 1978;7: 106-9.

12 Jackson BT, Kinmonth JB. Pes cavus and lymphoedema..7 Bone J7oint Surg [Br] 1970; 52: 518-20.

13 Kolin T, Johns KJ, Wadlington WB, Butler MG, SunlapMA, Wright KW. Hereditary lymphedema and distichia-sis. Arch Ophthalmol 1991; 109: 980-1.

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16 Govaert P, Van Kets H, Goeteyn M. Perinatal manifesta-tions of maternal yellow nail syndrome. Pediatrics 1992;89: 1016-8.

17 Bloom D. Hereditary lymphedema (Noone-Milroy-Meige).Report of a family with hereditary lymphedema associatedwith ptosis of the eyelids in several generations. NY] Med1941; 41: 856-63.

18 Dahlberg PJ, Borer WZ, Newcomer KL, Yutuc WR.Autosomal or X-linked recessive syndrome of congenitallymphedema, hypoparathyroidism, nephropathy, prolaps-ing mitral valve, and brachytelephalangy. Amn 7 Med Genet1983; 16: 99-104.

19 Leung AKC. Dominantly inherited syndrome of micro-cephaly and congenital lymphedema. Cli't Genet 1985; 27:611-2.

20 Crowe CA, Dickerman LH. A genetic association betweenmicrocephaly and lymphedema. Amn 3 Med Genet 1986;24: 131-5.

21 Feingold M, Bartoshesky L. Microcephaly, lymphedemaand chorioretinal dysplasia: a distinct syndrome? Aos YMed Genet 1992; 43: 1030-1.

22 Avasthey P, Roy SB. Primary pulmonary hypertension,cerebrovascular malformation, and lymphoedema feet in afamily. Br Heart] 1968; 30: 769-75.

23 Hourihane JO, Bennett CP, Chaudhuri R, Robb SA,Martin ND. A sibship with a neuronal migration defect,cerebellar hypoplasia and congenital lymphedema.Neuropediatrics 1993; 24: 43-6.

24 Hennekam RC, Geerdink RA, Hamel BC, et al. Autosomalrecessive lymphangiectasia and lymphedema, with facialanomalies and mental retardation. Am 7 Med Genet 1989;34: 593-600.

25 Optiz JM, Reynolds JF, Fitzgerald JM. Mandibulofacialdysostosis or bilateral hemifacial microsomia with hearingloss, telecanthus, tetramelic postaxial hexadactyly,congenital hypotonia and lymphedema with joint hyper-mobility, and pigmentary dysplasia: a new syndrome?Am]tYMed Genet 1989; 33: 433-5.

26 Aagenaes 0, Sigstad H, Bjorn-Hansen R. Lymphoedema inhereditary recurrent cholestasis from birth. Arch Dis Child1970; 45: 690-5.

27 Corbett CRR, Dale RF, Coltart DJ, Kinmonth JB.Congenital heart disease in patients with primary lym-phoedemas. Lymphology 1982; 15: 85-90.

28 Kinmonth JB, Young AE, Edwards JM, O'Donnell TF,Lea Thomas M. Mixed vascular deformities ofthe lower limbs, with particular reference to lympho-graphy and surgical treatment. Br Y Suirg 1976; 63:899-906.

29 Servelle M. Klippel and Trenaunay's syndrome. 768 oper-ated cases. Ann Surg 1985; 201: 365-73.

30 Levine C. Primary disorders of the lymphatic vessels - aunified concept. .7 Pediatr Surg 1989; 24: 233-40.

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33 Smeltzer DM, Stickler GB, Schirger A. Primary lym-phedema in children and adolescents: a follow-up studvand review. Pediatrics 1985; 76: 206-18.

34 Kinmonth JB, Wolfe JH. Fibrosis in the lymph nodes inprimary lymphoedema. Ann R Coll Surg Enigl 1980; 62:344-54.

35 Kinmonth JB, Eustace PW. Lymph nodes and vessels inprimary lymphoedema. Ann R Coll Suirg Engl 1976; 58:278-84.

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37 Doldi SB, Lattuada E, Zappa MA, Pierri G, Favara A,Micheletto G. Ultrasonography of extremity lym-phedema. Lymnphology 1992; 25: 129-33.

38 Weissleder H, Weissleder R. Interstitial lymphangiography:initial clinical experience with a dimeric nonionic contrastagent. Radiology 1989; 170: 371-4.

39 Partsch H, Stoberl C, Urbanek A, Wenzel-Hora BI. Clinicaluse of indirect lymphography in different forms of legedema. Lymphology 1988; 21: 152-60.

40 Weissleder R, Thrall JH. The lymphatic system: diagnosticimaging studies. Radiology 1989; 172: 315-7.

41 Weissleder H, Weissleder R. Lymphedema: evaluation ofqualitative and quantitative lymphoscintigraphy in 238patients. Radiology 1988; 167: 729-35.

42 McNeill GC, Witte MH, Witte CL, et al. Whole-bodylymphoscintigraphy: preferred method for initial assess-ment of the peripheral lymphatic system. Radiology 1989;172: 495-502.

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Carbamazepine, phenytoin, and the fetus

The fetal hydantoin syndrome was first described in 1975.' It hasbeen estimated to occur in between 6 and 30% of at risk babies.Reports of adverse effects from carbamazepine in pregnancyhave been less common. A report from Toronto (Dennis Scolnikand colleagues, J7ournal of the American Medical Association 1994;271: 767-70) compares children born after exposure duringpregnancy to either phenytoin or carbamazepine used as singledrugs. In a prospective study the children of 34 mothers whotook phenytoin in pregnancy were compared with those of 36who took carbamazepine and 70 paired mothers matched forage, parity, gravidity, and social class, who took only non-terato-gens. The children were assessed between 18 and 36 months ofage using Bayley or McCarthy scales of development andReynell language scales.Mean IQ was 103d1 in the phenytoin-exposed children and

11 3 4 in their paired controls. In children who had been exposedas fetuses to carbamazepine the mean IQ was 111-5 and in theirpaired controls it was 1 14-9. The difference was significant onlyfor the phenytoin group (p<0 05). Seven of the phenytoinchildren had features of the fetal hydantoin syndrome. An IQ of84 or less was found in seven of the 34 children in the phenytoingroup and one of their controls (p< 00 1). (Of the seven childrenwith fetal hydantoin syndrome two had IQ -84.) Such an IQwas found in three of the 36 carbamazepine-exposed childrenand one of their controls. The phenytoin-exposed children alsoperformed poorly on tests of verbal comprehension and expres-sive language. There was no significant difference between trialmothers and controls as regards IQ or social class.The authors suggest that carbamazepine should be preferred

to phenytoin in pregnancy. Most paediatricians prefercarbamazepine anyway.

ARCHIVIST

1 Hanson JW, Smith DW. The fetal hydantoin syndrome. I Pediatr 1975; 87: 285-90.

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