JMed Genet 1995;32:7-13

The profile of major congenital abnormalities inthe United Arab Emirates (UAE) population

L I Al-Gazali, A H Dawodu, K Sabarinathan, M Varghese

AbstractThe aim of this study was to establish theprofile ofmajor congenital malformationsin the United Arab Emirates (UAE) popu-lation which has a high rate of con-sanguinity. All births with birth weightabove 500 g in the three hospitals in the AlAin Medical District of UAE were pro-spectively studied from January 1992 toJanuary 1994. About 98% of the births inthe district occur in these three hospitals.Detailed family history and clinical andrelevant laboratory investigations were re-corded in each case. Necropsy was notpermitted. The major malformations wereclassified as multiple or isolated single sys-tem abnormalities as well as genetic ornon-genetic disorders. Ofthe 16 419 birthswhich occurred during the two yearperiod, 173 (10.5/1000 births) had majormalformations, 90 (52%) had multiplemalformations, and 83 (47-97%) had in-volvement ofa single system. Ofthe infantswith multiple malformations, 43 had re-cognised syndromes, most of which areautosomal recessive disorders with a highfrequency ofrare syndromes. Twenty eight(31%) had chromosomal abnormalities.The most common systems involved ininfants with isolated single system mal-formations include gastrointestinal (33),central nervous system (17), and cardio-vascular (10). While the consanguinity ratewas similar (57% v 54%), the frequency offirst cousin marriages was much higher(51% v 30%) in the study group comparedwith the figures for the general population.The consanguinity rate was highest amongthe syndrome cases, and related parentswere more likely to have infants with mul-tiple malformations than an isolated singlesystem abnormality with a relative risk of1*69 (95% CL 1.27-2-24). Genetic factorscould be implicated in 116 (67%) ofthe 173cases ofmajor malformations and 49 (28%)were potentially preventable. The studysuggests that genetic disorders account fora significant proportion ofcongenital mal-formations in the UAE and, thus, a geneticservice should be provided as part of thepreventive care programme.

(J Med Genet 1995;32:7-13)

Congenital malformations are structural ab-normalities of prenatal origin that result fromdefective embryogenesis or deviation from nor-mal development. The pattern and frequency

of different congenital abnormalities vary fromone country to another depending on geo-graphical, ethnic, and socioeconomic char-acteristics of the population studied. Suchstudies are useful for planning health care,including preventive programmes and edu-cational and rehabilitation needs of the popu-lation. Recent advances in the diganosis ofcongenital abnormalities has led to the iden-tification of many more dysmorphic syn-dromes. In addition, the improvement inprenatal diagnostic techniques has led to anincrease in the number of congenital ab-normalities which can be prevented.'The population of the United Arab Emirates

(UAE) is a mixture of different ethnic groups.The majority are Arab Muslims with a con-sanguinity rate of 54%; 30% of marriages arefirst cousin marriages.' These consanguinityfigures were independently reproduced in apilot study from Al Ain Medical District (Al-Gazali, unpublished data). Currently, there areno preventive programmes for congenital ab-normalities and many women continue to re-produce after the age of 40 years. Attemptingto provide genetic counselling for families ofchildren with congenital malformations in thispopulation has highlighted several issues.These included a lack of accurate informationon the genetic and non-genetic causes of mal-formation, and a lack of awareness by bothfamilies and the health authorities of theimportance of genetic counselling in the pre-vention of congenital malformations.The aim of this study was to establish the

incidence and pattern of congenital ab-normalities in the UAE population, as well asthe proportion of anomalies in which geneticfactors are implicated, in order to identify theappropriate strategies for prevention.

Materials and methodsA study of 16 419 consecutive live and still-births over 500 g birth weight at the three mainhospitals in Al Ain, UAE was carried out overa two year period from January 1992 to January1994. All babies were routinely examinedwithin 48 hours of delivery. All cases of severecongenital abnormalities which were either sus-pected or diagnosed within the first few days(up to one week) were registered. Only majormalformations were included in the study.These were defined as those abnormalities thatif uncorrected or uncorrectable significantlyimpair normal body functions or reduce normallife expectancy.3 Congenital dislocation of thehip was not included in this study. The diag-nosis of congenital abnormality was based onclinical assessment by an experienced neo-

Department ofPaediatrics, Faculty ofMedicine and HealthSciences, UAEUniversity, PO Box17666, Al Ain, UnitedArab EmiratesL I Al-GazaliA H Dawodu

Department ofPaediatrics, Al AinHospital, Ministry ofHealth, Al Ain, UAEK Sabarinathan

Department ofPaediatrics, OasisHospital, Al Ain, UAEM Varghese

Correspondence to:Dr Al-Gazali.Received 6 May 1994Revised version accepted forpublication 11 August 1994

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Table I Major congenital abnormalities in 16 419 birthsin the UAE

Type No IncidencellOOO births

MultipleSyndromes 43 2-61Sequences 12 0 73Chromosomes 28 1-70Association 1 0-06Complex 1 0-06Unknown 5Subtotal 90 5-48

Single systemCardiovascular 10 0-60Central nervous system 18 1-07Gastrointestinal 33 2-00Respiratory 2 0-121Genitourinary 7 0-42Musculoskeletal 5 0 30Skin 4 0 24Eye 2 0-12Tumours 2 0-12Subtotal 83 5 05Total 173 10-5

Table 2 Multiple abnormalities in the UAE

Type No of cases Family history(parent or sib)

(1) Syndromes(A) Autosomal donminant

Holt-OramCongenital myotonic dystrophyRobinowEDS ISubtotal

(B) Autosomal recessive

JoubertGoldenharLarsenOSMEDRobertsWrinkly skin syndromeEDS VIISMAOphthalmoacromelia01+ optic atrophy + retinopathyOsteodysplastic primordial dwarfism II

Osteodysplastic primordial dwarfism IKyphomelic dysplasia + tricuspid atresiaCongenital adrenal hyperplasiaChondrodysplasia punctataMarden WalkerCerebro-oculofacioskeletalShort limb dwarfism ?typeShort rib-polydactyly IIIUnknownSpondylothoracic dysplasia01 + dysmorphic featuresCystic kidney and ventriculomegalySubtotal

(C) EnvironmentalCongenital rubella

(D) SporadicNoonanSturge Weber

(E) Unidentified aetiologyRobin sequence + radial aplasiaTotal

(2) Chromosomal abnormalitiesTrisomy 18Trisomy 21Trisomy 1345,XO (Turner's)Unbalanced translocation5p- (cri du chat)Total

(3) SequenceHoloproscencephalyPotter'sPrune bellyPierre RobinAmniotic bandTotal

(4) AssociationCHARGE

(5) ComplexesPoland

(6) Undefined abnormalities

2

122

6

2

2

2

4

2

1

2

4l

21

21

32

2

in one

+

+

+ i n

43

319

1221

28

+

2612112

natologist or clinical geneticist or both and theLondon Dysmorphology Database (LDDB)4was consulted when indicated. Chromosomeanalysis was performed on all babies with mul-tiple abnormalities and dysmorphic features.Other appropriate investigations were per-formed when indicated. Necropsy was not car-ried out because it is not allowed. For eachcase, a detailed pregnancy and family history,including the level of consanguinity, was ob-tained by interviewing the parents.Each abnormal baby was classified into one

of two major groups.

(1) Isolated abnormalities include ab-normalities affecting a single body site.

(2) Multiple abnormalities are those ab-normalities that affect more than one bodysite. These are further divided into:(A) Syndromes which are further sub-

divided according to their aetiologyinto monogenic, chromosomal, en-vironmental, and syndromes of un-identified aetiology.

(B) Associations, which are disorderscharacterised by the non-randomoccurrence of several anomalies butwhich do not constitute a specificsyndrome, for example, CHARGE.

(C) Sequences include cases in whichthe associated anomalies can be in-terpreted as a consequence of aprimary malformation.

(D) Complexes are anomalies of severaldifferent structures, all of which lietogether in the same body regionduring embryonic development.

(E) Unrecognisable patterns of multipledefects including patterns of mul-tiple abnormalities that do not fitinto any of the above categories.

ResultsThere were 173 babies with major congenitalabnormalities identified during the two yearperiod, giving an incidence of 10 5/1000 births.Six of these were stillbirths and 41 died in theneonatal period. There were 90 babies withmultiple congenital abnormalities and 83 ba-bies with isolated malformations. These aresummarised in table 1.

MULTIPLE ABNORMALITIES (90 BABIES)(A) Syndromes (43 babies)The total number of babies who had a re-cognised syndrome was 43 (2-6/1000). Thirtytwo of these were autosomal recessive, six wereautosomal dominant, two had congenital in-fection, and two were sporadic. One baby hadthe newly recognised syndrome of radial aplasiaand Robin sequence where the aetiology isstill uncertain.5 The different syndromes aresummarised in table 2.There were four babies with spinal muscle

atrophy presenting with arythrogryposis mul-tiplex, and the diagnosis was confirmed in allof them by muscle biopsy. In one of thesebabies there was, in addition, bilateral femoral

1-1 - ----

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The profile of major congenital abnormalities in the United Arab Emirates (UAE) population

fracture noted soon after birth. This baby mighthave the same syndrome as described by Bor-ochowitz et al.6 Of the two cases of Joubertsyndrome, one had a similarly affected sib.There was a set of twins with osteogenesis

imperfecta (01) presenting with multiple frac-tures and limb deformities, as well as dys-morphic features which included hyper-telorism, very short, upturned nose, extremelyhighly arched palate with thick ridges, andclinodactyly. There was multiple consanguinityin the family and three other affected sibs, withonly one surviving to the age of 12 years. Theclinical and radiological features in this familydid not fit any of the recognised types of 01and collagen studies are in progress to definethe type of 01. The baby with Goldenhar syn-drome (usually inherited as AD) had anotheraffected sib and both parents were normal andconsanguineous and, thus, was included in theAR syndrome.The infant with wrinkly skin syndrome had

two affected sibs and consanguineous parents.The parents of the baby with short rib-poly-dactyly syndrome III (Verma-Naumoff) hadcomplex consanguinity in the family with ahistory of three babies dying soon after birthwith similar features. Another infant born tothese parents had bilateral cataracts and mas-sive intracranial calcification with hepato-splenomegaly and was diagnosed as havingcongenital infection. There were no survivingchildren in this particular family.Many of the recessive syndromes diagnosed

were very rare. For example, ophthalmoacro-melia was diagnosed in one baby. Anotherinfant had a rare syndrome of osteogenesisimperfecta, optic atrophy, and retinopathy anda similarly affected sib. These cases arereported elsewhere.78 There were two casesof microcephalic osteodysplastic primordialdwarfism types I and type II. Both had verycomplex consanguinity in the family and therewas a history of a sib dying with similar featuresin the former. The case of otospondylomega-epiphyseal dysplasia (OSMED) had two affec-ted sibs and has been previously published.9The baby with chondrodysplasia punctata hadtwo affected sibs and detailed investigation inone of them showed isolated DHAP-AT de-ficiency. This new peroxisomal disorder hasbeen reported twice previously.'""' Other syn-dromes diagnosed in which there was con-sanguinity and an affected sib included Larsensyndrome, EDS type VII, and cerebro-oculofacioskeletal syndrome. The baby withhydrocephalus and bilateral cystic kidneys hadno other associated abnormalities. The familyis highly inbred with a history of a previouslyaffected baby and another similarly affectedstillbirth who was not included in the study(born afterjanuary 1994). This family probablyhas the same syndrome of ventriculomegalyand cystic kidneys described by Reuss and DenHollander. " The diagnosis in two babies wasuncertain. However, since the parents wereconsanguineous with a history of three still-births who had similar features, these wereincluded with the recessive syndromes. Themother of the infant with congenital myotonic

dystrophy had typical features ofmyotonic dys-trophy and two previously affected children.The cases of Robinow syndrome had an affec-ted father and one affected sib.

(B) Chromosome abnormalities (28 cases)Abnormal karyotypes were detected in 28 ba-bies as summarised in table 2. There were 19cases of Down's syndrome giving an incidenceof 1-15/1000 which is the same as in otherparts of the world. All were of the non-dis-junction type. Nine of the mothers were abovethe age of 35 years.There was one case of trisomy 13. The

mother had a history of previous stillbirth withmultiple abnormalities but no cytogenetic ana-lysis was performed. She was found to have a13; 14 translocation.There were two cases of unbalanced trans-

location and one case of cri du chat syndrome(5p-).

(C) Sequence (12 cases)Twelve babies had multiple abnormalities as aconsequence of a single malformation (table2). Six had Potter's sequence, four resultingfrom renal agenesis, one from cystic dysplastickidney, and one from urethral obstruction.Diagnosis was made by renal ultrasound. Twoinfants had holoprosencephaly and chro-mosome analysis was unsuccessful in both.

(D) Association and complexes (2 cases)There was one case of CHARGE associationand another of Poland anomaly (table 2).

(E) Unrecognised multiple malformationsFive infants in the study had abnormalitieswhich could not be classified either becausethe investigations were incomplete or the ab-normalities did not conform to any disorder orthe syndrome was not known to the authors(table 2).

ISOLATED ABNORMALITIES (83 CASES)The malformations affecting a single systemfound in 83 patients are summarised in table 3.

(A) Cardiovascular (10 cases)The diagnosis was based on echocardiographyin all cases.

(B) Central nervous system (18 cases)Anencephaly and meningomyelocele werepresent in 12 babies. Five cases were diagnosedprenatally by ultrasound late in pregnancy. Twobabies had autosomal recessive microcephaly,with a similarly affected sib in one of the cases.There was a case of severe microcephaly andcomplex brain malformation including po-lymicrogyria, hypoplasia of the cerebellum andbrain stem, with agenesis of corpus callosum.There was a history of three sibs who died

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Table 3 Single system involvement among infants withmajor malformations

Type No

(A) CardiovascularSingle ventricleVSD + PDAVSDTransposition of great arteriesDextrocardia + situs inversusComplex congenital heart diseaseSubtotal

222

210

(B) Central nervous systemAnencephalyMeningomyeloceleMicrocephalyCerebrocerebellar lissencephaly and agenesis of

corpus callosumPolymicrogyria, hypoplasia of cerebellum and

brain stem, and agenesis of corpus callosumDandy-Walker malformationSubtotal

(C) GenitourinaryMultiple dysplastic kidneyPosterior urethral valveHydronephrosis (PUJ obst)Subtotal

(D) MusculoskeletalDistal arythrogryposisSevere talipesCraniosynostosisFocal femoral hypoplasiaSubtotal

(E) GastrointestinalCleft lip and palateDiaphragmatic herniaOesophageal atresia + tracheo-oesophageal

fistulaImperforate anusIntestinal obstructionOmphaloceleSubtotal

(F) RespiratoryLung hypoplasiaLaryngomalaciaSubtotal

(G) SkinEpidermolysis bullosaPeeling skin syndromeSubtotal

(H) EyesMicrophthalmia

(I) TumoursSacrococcygeal teratomaCervical teratomaSubtotal

7521

18

4

27

2

18

5

10105

431

33

2

224

2

2

of similar malformations. The parents were

consanguineous and of Omani origin.

(C) Genitourinary (7 cases)Four infants had multiple cystic dysplastic kid-ney, diagnosed by ultrasound. There was a case

of posterior urethral valve and two cases ofhydronephrosis owing to pelviureteric junction(PUJ) obstruction.

(D) Musculoskeletal (5 cases)Distal arythrogryposis was present in one babywhose mother was also affected. There was

one case each of focal femoral hypoplasia andcraniosynostosis and two cases of severe talipes.

(E) Gastrointestinal (33 cases)The commonest among these was dia-phragmatic hernia (10 cases). All the infantswere otherwise normally formed. The defectswere confirmed at surgery. There were fivecases of oesophageal atresia or tracheo-oeso-

Table 4 Genetic contribution to congenital abnormalitiesin the UAE

Type No ofcases

Single geneTotal 47

Autosonmal recessiveJoubert syndrome 2Goldenhar syndrome ILarson syndrome ISpondylothoracic dysplasia 1OSMED IRoberts' syndrome 2Kyphomelic dysplasia 1CAH 2Chondrodysplasia punctata IEDS VII 2Wrinkly skin syndrome ISMA 401 + optic atrophy + retinopathy IOphthalmoacromelia IOsteodysplastic primordial dwarfism 2Marden Walker syndrome ICOFS I0! 2Short rib-polydactyly III IUnknown syndrome 2Microcephaly 3Epidermolysis bullosa 2Netherton syndrome 2Cystic kidney and ventriculomegaly ISubtotal 38

Possible ARLissencephaly IShort limb dwarfism I

Autosomal dominantCongenital myotonic dystrophy IHolt-Oram 2Robinow 2EDS I 1Distal arythrogryposis ISubtotal 7

Chromosomal abnormalities 28Multifactorial

Congenital heart disease'4 10Neural tube defects'5 12Renal agenesis'6 4Severe talipes equinovarus deformity'7 2Holoprosencephaly'" 2Cleft lip/palate'5 10Coronal craniosynostosis20 I

Subtotal 41Total 116

phageal fistula or both, four cases of im-perforate anus, and 10 cleft lip/palate. Thebaby with omphalocele looked normal and hadnormal chromosomes.

(F) Respiratory (2 cases)Lung hypoplasia was present in one infant withnormal kidneys. The other case was an infantwith laryngomalacia who was otherwise nor-mal.

(G) Skin (4 cases)Two infants had epidermolysis bullosa dy-strophica. Two sibs whose parents are con-sanguineous had Netherton syndrome orpeeling skin syndrome. One of them presentedas harlequin baby.'3

(H) OthersTwo infants had simple microphthalmia withno other abnormalities. "TORCH" in-vestigation was normal in both. There wasone case each of sacrococcygeal teratoma andcervical teratoma, both proven by histology.

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GENETIC CONTRIBUTION TO CONGENITALABNORMALITIESGenetic factors can be implicated in 116 (67%)of the 173 cases (table 4). There were 47 cases

caused by a single gene defect (27-1%) and 38of these were caused by an AR gene (21 9%),two were possibly caused by an AR gene(1 2%), and seven by an AD gene (4%). Chro-mosomal abnormalities accounted for 16 1%(28 babies) and multifactorial inheritance23-6% (41 babies) of the cases.

CONSANGUINITY LEVELThere were 99 babies with consanguineousparents giving a consanguinity rate of 57% inthe study group which is slightly higher thanthe rate in the general population.2

Fifty (51 %) of the 99 babies had first cousinparents compared with 30% in the generalpopulation.2 Eight babies had complex con-

sanguinity in the family, these were the twinswith OI, and one case each of short rib-poly-dactyly III syndrome, congenital infection, os-

teodysplastic primordial dwarfism type I andII, cystic kidney and ventriculomegaly, andan undiagnosed syndrome with three previousstillbirths who were similarly affected.There was one uncle-niece marriage and

three double first cousin marriages. In the re-

maining 37 cases, the consanguinity levelamong the parents ranged from first cousinonce removed to second cousin to more distant.The occurrence of consanguinity was 38

(88%) in the 43 syndrome cases, 26 (55%) inthe other multiple malformation group, and35 (42%) in those with isolated abnormality.These differences were highly significant (x2 =24-06, df 2, p<00001). Similarly, con-

sanguineous parents were more likely to haveinfants with multiple malformations than isol-ated abnormalities with a relative risk of 1-69(95% CL= 1-27-2-24).

HOW MANY ABNORMALITIES WERE POTENTIALLYPREVENTABLE?

Nine babies with Down's syndrome whosemothers were above 35 years of age could havebeen diagnosed antenatally using the triple testfollowed by chorionic villus biopsy (CVB) or

amniocentesis. Similarly, the 12 infants withneural tube defects could have been detected inutero using oc fetoprotein and ultrasonography.The case of trisomy 13 whose mother had a

13;14 translocation and a history of stillbirthwith malformation should have had CVB or

amniocentesis.There were six cases with a positive family

history and abnormalities that are detectableby antenatal ultrasound. These include thebaby with microcephaly and complex CNSmalformation (three sibs affected), Joubert syn-

drome (one sib affected), short rib-polydactylyIII (three sibs affected), the twins with 01

(three sibs affected), and the baby with cystickidneys and ventriculomegaly.Three other cases with previously affected

sibs had disorders that could be diagnosedprenatally using biochemical or molecular stud-

ies; these include CAH (one sib affected), con-genital myotonic dystrophy (mother and twosibs), and the baby with chondrodysplasiapunctata with isolated deficiency of DHAP-AT.

Furthermore, genetic counselling could havechanged the reproductive decision of the par-ents of 18 babies with previously affected sibsand abnormalities which are not yet detectableby prenatal testing.

Therefore, the total number of abnormalitieswhich were potentially preventable was 49(28%).

DiscussionThe incidence of congenital abnormalities inthis study was 10-5/1000 which is comparableto or even slightly less than studies from othercountries.2122 However, this figure could be anunderestimate since only 43% of all congenitalabnormalities are diagnosed at birth,23 andsome internal malformations are only re-cognised by necropsy which is not permittedhere. It is of interest that the incidence ofabnormalities caused by a single gene defect inthis study was high (27%). Other studies foundan incidence of such abnormalities to rangefrom 7 to 25%.2425 This is probably because ofracial differences of the population studied,for example the high incidence of single genedisorders in Holmes's study (25%) was theresult of the common prevalence of postaxialpolydactyly type b in the black population. Infact, if this abnormality is excluded from thedata in that study, the incidence of single genemutations drops to 8%.2425The high incidence of single gene disorders

in our study is accounted for by the incidenceof autosomal recessive abnormalities in thispopulation (21-9%). If the two possibly re-cessive disorders were included, the incidenceof autosomal recessive abnormalities will in-crease to 23%. A similar study from Abu Dhabifound the incidence ofcongenital abnormalitiesto be 12 9/1 000 with a relatively high frequencyof rare disorders.26The high incidence of major malformations

caused by rare recessive genes is probably re-lated to the high level of consanguinity in thepopulation of UAE. Although the rate of con-sanguinity in the study group was only slightlyhigher than that of the general population, thefrequency of first cousin marriages of 51% wasparticularly high when compared with 30%in the general population.2 In addition, theconsanguinity level was highest in the syndromegroup (88%). This group consisted mainly ofthe AR syndromes.

Studies of congenital malformations indifferent parts of the world have shown that therisk for malformation in first cousin marriagesincreases to 5 to 8% compared to a 2 to 3%frequency in the general population.27-32 Jaberet al32 found a significant increase in the in-cidence of major malformation in relation tothe closeness of the parental relationship in anIsraeli Arab village (15-8% in the offspring offirst cousin marriage compared to 8-3% inintra-village non-related marriages and 5-8%

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12Al-Gazali, Dawodu,Sabari nathan, Varghese

in the offspring of intervillage marriages). Inour series, although the very high level of con-sanguinity, particularly first cousin marriages,did not seem to increase the overall incidenceof congenital malformation diagnosed in thefirst week of life, there was a definite increasein the incidence of malformation caused byrare recessive genes. Further, the parents ofinfants with inherited syndromes and multiplemalformations group were about twice as likelyto be related than the parents of infants withisolated or single system abnormalities.

It is well known that the risk of a child havinga recessively inherited condition is higher if theparents are related, and the more closely relatedthe parents are, the higher the risk. Theseobservations were exploited by human gen-eticists to devise a method to map rare recessivetraits by linkage analysis.33 The concept ofhomozygosity mapping, which was initially sug-gested by Smith34 and later elaborated byLander and Bostein,"3 has been successfullyused to map many rare recessive disorders.3639Since the majority of the congenital ab-normalities in this series are caused by rarerecessive genes, and the level of first cousinmarriages and complex consanguinity are highamong the parents of affected children, it maybe useful for future research in the UAE toevaluate such families further in order to mapthe genes for these recessive syndromes. Thiswill be important in the prevention of thesedisorders.

Twenty-eight percent of the abnormalities inthis study were preventable using pregnancyscreening for neural tube defect, screeningolder mothers for Down's syndrome, or byusing the family history as an indicator forgenetic counselling and prenatal diagnosis.

Czeizel et all showed that preventive methodsare currently available for 70% of congenitalabnormality entities and that 60% of thesedevelopmental defects are preventable. In ad-dition, other reports suggest that 70 to 80% ofsevere congenital abnormalities may be de-tected by routine fetal anomaly scanning bytrained non-medical operators with modemequipment.40 Ifsuch approaches become widelyused, the proportion of congenital ab-normalities that could be prevented would in-crease considerably.There are no preventive programmes in the

UAE and genetic services are inadequate. Thehigh incidence of abnormalities with a highrecurrence risk (single gene) in this study in-dicates that there is a need to develop a com-prehensive preventive programme forcongenital abnormalities in this country. Apartfrom the routine maternal care in pregnancy,there should be a special and sensitive edu-cational programme about the genetic con-sequences of consanguineous marriage.Genetic counselling supported by the avail-ability of antenatal screening and prenatal diag-nostic technology when appropriate should bean essential component of such a programme.This should form the basis of a communitybased genetic service which is an integral partof preventive medical care.

In conclusion, this prospective study has pro-

duced a detailed analysis of the pattern ofcongenital malformation in a Middle Easternmedical district. The high incidence of geneticfactors in the causation of the malformationsuggests an urgent need for a comprehensivegenetic service as part of the health care pro-gramme.

1 Czeizel A, Intody Z, Modell B. What proportion of con-genital abnormalities can be prevented.BMr 1993;306:499-503.

2 Fahmy NA, Benson PE, Al-Garrah DB. Consanguinity inthe UAE: prevalence and analysis of some risk factors.Emir MedJ7 1993;1(suppl):39-41.

3 Aylsworth AS. Genetic counselling for patients with birthdefects. Pediatr C/in North Am 1992;39:229-53.

4 Winter RM, Barraitser M. London Dysmorphology Database.JMed Genet 1987;24:509-10.

5 Bruce A, Winship I. Radial ray defect and Robin sequence:a new syndrome. C/in Dysmorphol 1993;2:241-4.

6 Borochowitz Z, Glick B, Blazer S. Infantile spinal muscularatrophy (SMA) and multiple congenital fractures in sibs:a lethal new syndrome.JrMed Genet 199 1;28:345-8.

7 Al-Gazali LI, Sabarinathan K, Khidir A. Microphthalmiaand distal limb abnormalities in a child of consanguineousparents.Clin Dysmorphol 1 994;3:258-62.

8 Al-Gazali LI, Sabarinathan K, Nair K. A syndrome of os-teogenesis imperfecta, optic atrophy, retinopathy and se-vere developmental delay.Clin Dysmorphol 1994;3:55-62.

9 Al-Gazali LI, Lytle W. Otospondylomega epiphyseal dys-plasia (OSMED): report of three sibs and review of theliterature.Clin Dysmorphol 1994;3:46-54.

10 Wanders RJA, Schemacher H, Heikoop J, Schutgens RB,Tager JM. Human dihydroxyacetonephosphate acyl-transferase deficiency: a new peroxisomal disorder. _7 In-herited Metabol Dis 1992;15:389-41.

11 Barr DGD, Kirk JM, Al Howasi M, WandersRJ, SchutgensRBH. Rhizomelic chondrodysplasia punctata with isolatedDHAP-AT deficiency. Arch Dis Child 1993;68:415--17.

12 Reuss A, Den Hollander JC. Prenatal diagnosis of cystickidney disease with ventriculomegaly: a report of six casesin two related sibships. Am I Med Genet 1989;33:385 -9.

13 Lestringant G, Hertecant J, Bossaert Y, Abdulrazzaq Y,Frossard P. A harlequin fetus evolving into a Comel-Netherton/peeling skin type B syndromc. Abstracts of theAcademy of Dermatology, San Francisco, 1994.

14 Harper PS.Practical genetic counselling. 4th ed. London:Butterworth Heinemann, 1993:241.

15 Harper PS.Practical genetic counsellintg. 4th ed. London:Butterworth Heinemann, 1993:177.

16 Carter CO, Evans K, Pescia G. A family study of renalagenesis.7 Med Genet 1979;16:176-88.

17 Wang J, Palmer RM, Chung S.The role of major genes inclub foot. Am Hum Genet 1988;42:772--6.

18 Benke PJ, Cohen MM. Recurrence of holoprosencephalyin families with family history. Clin Genet 1983;24:324--8.

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20 Carter CO, Till K, Fraser R. A family study of cranio-synostosis with probable recognition of a distinct syn-drome. Med Genet 1982;19:280-5.

21 Stevenson AC, Johnson HA, Stewart MP, Golding ARE.Congenital malformations. A report of a study of seriesof consecutive births in 24 centres. Bull WHO 1966;34(suppl):25-9, 90-2.

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