JMed Genet 1997;34:453-458

Intelligence and psychosocial adjustment invelocardiofacial syndrome: a study of 37 childrenand adolescents with VCFS

A Swillen, K Devriendt, E Legius, B Eyskens, M Dumoulin, M Gewillig, J P Fryns

AbstractWe report data on a group of 37 VCFSpatients with specific reference to theirintelligence, behaviour, and social compe-tence. Fifty five percent of the childrenhad a borderline to normal IQ. Mentalretardation (defined as IQ <70 or >-2 SDbelow the mean) was found in 45%. In themajority, the mental retardation was mild(38%) and only two patients had moderatemental retardation. Severe mental retar-dation seems to be rare in VCFS. Thepresent study shows also that the inci-dence of mental retardation is muchhigher in the familial than the de novogroup. Intelligence is not correlated withthe presence or absence of a heart defect.Significantly higher verbal IQs than per-formance IQs (probably related to deficitsin visuospatial-perceptual functioning)were found. Problems in social-emotionalfunctioning and attention were also found.Further longitudinal studies are neces-sary to provide an accurate prognosis andappropriate intervention for VCFS chil-dren.( Med Genet 1997;34:453-458)

Keywords: velocardiofacial syndrome; intelligence; be-haviour; social competence

Centre for HumanGenetics, UniversityHospital Gasthuisberg,Herestraat 49, B-3000Leuven, BelgiumA SwillenK DevriendtE LegiusJ P Fryns

Division of PaediatricCardiology, UniversityHospital Gasthuisberg,Herestraat 49, B-3000Leuven, BelgiumB EyskensM DumoulinM Gewillig

Correspondence to:Dr Fryns.

Received 1 July 1996Revised version accepted forpublication 7 January 1997

The velocardiofacial syndrome (VCFS) was

initially described by Shprintzen et al' in 1978as a multiple congenital malformation syn-drome. Its major features are a cleft palate or

velopharyngeal insufficiency, cardiac anoma-lies, typical facial appearance, learningdisabilities, or mental retardation. The discov-ery of a submicroscopic deletion in chromo-some 22ql 12 in the majority of patients hasconfirmed that VCFS is a specific syndrome. Inmost patients the deletion occurs de novo, butautosomal dominant inheritance with variableexpression has been observed. Both severelyand mildly phenotypically affected patientswith the 22ql 1 deletion have been observed.3So far, no predictive factors for the severity ofthe disorder have been identified.Although learning disabilities or mental

retardation have almost invariably been foundin VCFS, only one study in patients assessed ata craniofacial centre has so far specificallytested the cognitive abilities and language pro-files of these children.4

We report data on a group of 37 VCFSpatients with specific reference to their intelli-gence, behaviour, and social competence.

Material and methodsPATIENTSWe studied a group of 37 consecutivelydiagnosed children and adolescents withVCFS. Eleven were identified in a prospectivestudy of patients with a conotruncal heartdefect.5 The main presenting symptoms of theremaining 26 patients were as follows: congeni-tal heart defect in six, developmental delay ineight, behavioural problems in three, and velo-pharyngeal insufficiency in three. The remain-ing six patients were affected sibs of indexpatients.

Table 1 gives a summary of the age at time ofdiagnosis, origin of the deletion (familial or denovo), presenting symptoms, mental level/IQof the patients, and educational level of theparents.The study group consisted of 19 males and

18 females (n=37). Their age, at the time of thetesting, varied from 8 months to 20 years . Allpatients presented features of the VCFS and allhad a 22ql 1 deletion (shown by fluorescencein situ hybridisation using probe D0832).6 In25 of these 37 patients, the 22ql 1 deletion wasof de novo origin and in 12 of familial origin(nine maternal, three paternal).Two thirds of the children and adolescents

(24 or 65%) had a heart defect. Three childrenhad a cleft palate which was surgically repairedand nine children had a pharyngoplasty forvelopharyngeal insufficiency.

PSYCHOMETRIC TESTSWe completed a psychometric evaluation in all37 subjects aged between 8 months and 20years. Medical and psychosocial history wereobtained from medical records and parentalinterview. Data on intelligence were obtainedby formal IQ tests, and a behaviour rating scalewas completed by the parents. All childrenwere tested by the same person (AS) at home.

IntelligenceThe following intelligence tests were usedaccording to age: the youngest children (8-30months) were evaluated with the Bayley Devel-opmental Scales (BOS 2-30)7 (n = 11). TheMcCarthy Developmental Scales8 9 were usedin two children (aged 2 years 6 months and 3years 11 months, respectively) and theSnijders-Oomen Non-Verbal Tntelligence Test-

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Table 1 Description of the study group

PresentingNo Sex Age Fam symptonms Mental levellIQ EducM* EducF*

1 M 0;3 N Cardio screen Normal 4 32 F 0;4 N Cardio screen Delayed 3 43 F 1;6 N Cardio+dev delay Moderate MR 5 54 F 2;0 Y Dev delay Mild MR 1 25 F 2;0 N Dev delay+FD Borderline (86) 3 36 M 0;5 N Heart defect Borderline 5 57 M 2;10 N Dev delay Normal(100) 5 38 M 3;3 N Cardio screen Borderline(85) 3 39 M 0;1 Y Familial Mild MR 3 210 M 2;0 N Heart defect Normal (92) 4 411 M 3;1 1 N Heart defect Borderline (79) 1 212 F 3;6 N VPI Borderline (80) 3 313 F 4;7 N Dev delay Normal (90) 5 514 F 5;0 N VPI Normal (94) 3 415 M 5;8 N Cardio screen Borderline (76) 5 516 F 5;3 Y Familial Mild MR (59) 1 117 F 5;0 Y Dev delay Mild MR (61) 1 218 M 6;0 N Cardio screen Mild MR (65) 3 519 F 3;0 N Dev delay+FD Normal (100) 4 420 M 6;6 N Behavioural probl Mild MR (69) 3 321 F 5;0 Y VPI+short stature Mild MR (60) 1 222 M 6;4 Y Dev delay Moderate (<50) 2 323 M 8;5 Y Familial Severe MR (24) 1 124 M 9;6 N Cardio screen Borderline (75) 5 525 F 10;7 N Cardio screen Borderline (82) 5 526 M 9;0 N Cardio screen Normal (87) 3 427 M 9;3 Y Familial Mild MR (59) 2 328 F 8;0 Y Familial Mild MR (60) 2 129 F 7;0 N Behavioural probl Borderline (80) 5 530 F 10;0 N Heart defect Normal (86) 5 531 M 9;0 Y Cardio screen Mild (57) 2 132 M 12;0 N Behavioural probl Mild (69) 2 233 F 16;5 N Cardio screen Mild (55) 3 334 F 16;0 Y Cardio screen Borderline (77) 2 535 M 17;0 N Heart defect + Borderline (73)

short stature36 M 16;0 N Dev delay Mild MR (65) 4 537 F 20;8 Y Familial Normal (86) 2 5

Age=age at time of diagnosis, Fam=familial occurrence of the del(22ql 1), Y=Yes, N=No, Devdelay=developmental delay, Cardio screen=patients ascertained through systematic screening ofpatients with conotruncal heart disease, VPI=velopharyngeal insufficiency, Mental level/IQ=mental level/IQ of the patient, EducM=educational level of the mother, EducF=educationallevel of the father.tl=primary school or special school, 2=vocational training, 3=secondary technical school, 4=sec-ondary general school, 5=college/university.

Revised (SON-R)10 in two other children withgross delay in verbal development. TheWechsler Primary Preschool Scale of Intelli-gence (WPSSI)" was used in nine preschoolchildren (age range 4-6 years 5 months, meanage 6 years), the Wechsler Intelligence Scale forChildren-Revised (WISC-R)12 was used in 11school age children and young adolescents (agerange 7-16 years, mean age 12 years 4 months),and the Wechsler Adult Intelligence Scale(WAIS)3 in a 20 year old adolescent girl. TheTerman-Merrill intelligence scale'4 was used inone mentally retarded boy. Dutch norms wereused, except for the Terman-Merrill intelli-gence scale.

Behaviour and social competenceThe Dutch version of the Child BehaviourChecklist (CBCL)'5 was used to obtain stand-ardised reports of problem behaviour inchildren and adolescents. Parents of 25 pa-tients completed the CBCL 2-3 years (n=6) orthe CBCL 4-18 years (n= 19), according to thecorresponding age of their child. In ninechildren, CBCL data could not be collectedbecause the children were too young (<2 yearsof age). In the remaining three children, CBCLdata were incomplete, so that T scores couldnot be calculated. The CBCL consists of 112behaviours (problem items), and these are

scored as follows: 0 if the item is "not true" for

Table 2 Milestones in motor development in VCFS

IQ>70

Milestones in nmotor developnment Mean SEM

Sitting alone 8.It 9.6 1.064Crawling 8.7 12.0* 1.633Standing alone 13.4 13.6 1.208Walking alone 14.1 18.8** 1.447

*Significant p<0.05. **Significant p<0.01.tMean (according to Bayley Developmental Scales (2-30months).

the child, 1 if the item is "somewhat orsometimes true", and 2 if it is "very true oroften true". A total problem score is computedby summing all Os, is, and 2s. We used thecross informant syndrome constructs as re-ported by Achenbach." The results from thechecklist are transformed first into a totalproblem score, second into two subscores forrespectively internalising (withdrawn, somaticcomplaints, and anxious/depressed) and exter-nalising problem behaviour (delinquent andaggressive), and third into a profile of clusterswith specific problem behaviour (withdrawn,somatic complaints, anxious/depressed, socialproblems, thought problems, attention prob-lems, delinquent behaviour, and aggressivebehaviour).T scores (X=50, SD=10) were calculated for

each patient. For the total problem score, andthe internalising and externalising subscores, atotal T score of 63 or higher (90th centile orhigher) is considered to be in the "clinical"range. T scores (for the separate syndromes) inthe range of 70 or higher (>98th centile) arefound in populations with severe behaviouralor emotional problems. For the specific prob-lem clusters, a T score of 66 or higher (>93rdcentile) are considered to be of concern-"We also interviewed the parents and re-

viewed medical records and child welfare dataconcerning the early development of the child(motor and language milestones) and theschool performance, and the socioeconomicstatus (SES) of the parents (for example,educational level, current occupation).

STATISTICAL ANALYSISAnalysis of covariance, t tests, sign test, andScheff&'s post hoc test were performed whereindicated.

ResultsDEVELOPMENTAL HISTORY

In 13 children, the parents could not giveaccurate and complete information on devel-opmental milestones. Developmental datawere obtained on 24 children. The majority ofchildren had delayed motor and languagedevelopment. With regard to motor develop-ment, even the children with a normal toborderline intelligence (IQ >70) were statisti-cally significantly slower (compared with nor-mally developing peers) in reaching the mile-stones "crawling" and "walking alone" (table2).Data on language development (first words,

first sentences) could not be statistically tested,owing to missing data. The children with nor-

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mal and borderline IQ (IQ >70) spoke theirfirst words around 18 months (mean age) andfirst sentences around 36 months (mean age).The mentally retarded children spoke their firstwords at 32 months (mean age) and their firstsentences at 60 months (mean age, 5 years).

INTELLIGENCE AND SCHOOL PERFORMANCE

Intelligence and cognitive profileTwenty children (55%) had normal (IQ >86)(n=9) or borderline (IQ 71-85) (n=1 1) intelli-gence. In 18 of these 20 children (90%) the22ql 1 deletion was of de novo origin and in2/20 (10%) the deletion was familial (inheritedfrom their mother) (table 1). Seventeenchildren (45%) were mentally retarded (IQ<70). Fourteen of them had mild mental retar-dation (IQ=55-69), two were moderately men-tally retarded (IQ <50), and one child wasseverely mentally retarded (IQ=24). The meanIQ of the children in whom the presentingsymptom was developmental delay (n=8;familial deletion in three, de novo deletion infive) was 71.85, which is not significantlydifferent from the mean IQ of 69.05 of theremaining patients (n=29; familial deletion innine, de novo deletion in 20).

In the group of mentally retarded childrenand adolescents, the incidence of familial dele-tions (three paternal transmission, nine mater-nal transmission) was high (12/17 or 70.5%).Of the 25 patients with a de novo 22ql 1 dele-tion, only seven (28%) were mentally retarded,compared with 10 of the 12 patients (83.3%)with a familial transmission of the deletion.The incidence of mental retardation is thushigher in familial than in de novo cases: meanFSIQ of familial cases (n=9) was 63.2 (SD11.08) (fig 1) which is statistically significantlylower than the mean FSIQ of de novo cases(n=20) with an IQ of 79.8 (SD 11.8)(p<0.002, Student's t test). In this analysis, onepatient with a familial deletion and severemental retardation was excluded. A possiblerelationship of IQ with parental educationallevel was studied by covariance analysis. Whenwe corrected for the educational level of themother and father in a covariance analysis, themean FSIQ of familial cases was not statisti-cally significantly lower than the mean FSIQ ofthe de novo cases. However, when we correctedonly for educational level of the father, themean FSIQ of the familial cases was stillsignificantly lower than the mean FSIQ of thede novo cases.The mean FSIQ of the children with a heart

defect (n=17) was 77.2, and for the childrenwithout a heart defect mean FSIQ was 67.3,which is not statistically significant (Student's ttest, p=0.10447).Looking at the VIQ-PIQ differences, we

found for the total group (tested with Wechslerscales) (n=20) a statistically significant differ-ence between the average verbal IQ of 78 (SD14.7) and average performance IQ of 70 (SD11.3) (paired Student's t test, p<0.001). In thegroup of nine young children (mean age 6years, WPPSI results), we found a mean verbalIQ of 75.5 and a performance IQ of 70.2 (notsignificant). In the group of the 11 older

110 r

100 F

90gF

cn

LL

o Individual FSIQ score- Average FSIQ of the group

0

80 H0

70 H

00

00

0000

60 F0

50 H 0

40 H

Familal De novoInheritance

Figure 1 Intelligence of VCFS patients with a familialdeletion 22qll versus a de novo 22qll deletion.

children (mean age 12 years; WISC-R results)we found a mean verbal IQ of 79 and a meanperformance IQ of 69 (p<0.001).

Educational level and school performanceParents.The educational level of the parents offamilial cases was significantly lower than non-familial cases (p=0.00007, Kruskal-Wallis oneway ANOVA).

Children and adolescents. Of the total group of37 children and adolescents, 30 children attendschool. Thirteen (age range 3-16 years) attendregular classes: seven are now in preschool (onechild has repeated one class), three are inprimary school (two of them have repeated oneclass), and three are in secondary school (twohave repeated one class). All children receivespeech therapy with special attention to articu-lation, grammar, and syntax. Remedial teach-ing, especially for mathematics, is required formost of the children.The remaining 17 children (age range 5-16

years) attend special classes. Three children arein a special school for normal intelligentchildren with severe learning disabilities.Theremaining 14 attend schools for the mildly tomoderately mentally retarded. All receive anintensive programme for early reading, writing,and arithmetic, speech therapy, psychomotortherapy, and training in social skills andself-care.

BEHAVIOURIn the toddler group (children between 2 and 3years, n = 6), somatic complaints ("constipa-tion" and "eats poorly") and (social) with-drawal were reported in five of the six childrenon the CBCL. Only one child had a total Tscore within the clinical range (T >63).For the older children and adolescents

(n= 19), the mean T scores on the CBCL 4-18years for the total group on total problemscore, on internalising, externalising, and onthe different clusters of problem behaviour aregiven in table 3. Highest scores were found on"Social problems" (average T score of 64),

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Table 3 Average Tscores on the CBCL 4-18for the totalgroup (n=19)

T scores SEM

Total problem score 52.2 2.206Total internalising score 54.5 2.206Total externalising score 49.9 2.206Withdrawn 58.6 1.603Somatic complaints 54.9 1.603Anxious 54.3 1.603Social problems 64.7 1.603ThoughtAttentioiDelinqu,Aggressi

70

65

oH) 60

55

50

Figure 2

axis: WiAnx=atAtt=atteAgg=agitotal grosignica

"Attenand "'hoc st,the cluproblehigherbehavi2).

Fordistincderlinethe grn(IQ <

becausmental

In tichildre35) hai(T >(scores

foundprobleand "

iourallems",was al

<70) balread3foundWe als

non-clinical) on anxiety/depression for theolder children (11 years and older) with VCFS.

In the group of mentally retarded children(n=7), two out of seven (patients 16 and 18)had a total T score within the clinical range.Clinical scores on the syndromes (T >70) werefound on "Social problems" (n=5) and on"Attention problems" (n=3).

t problems 55.8 1.603 Discussionnproblems 64.1 1.603 In the present study of 37 patients with VCFS,ent behaviour 52.5 1.603ive behaviour 54.6 1.603 and a deletion in 22ql 1, we confirm that one of

the main clinical features of this syndrome islearning disability or mental retardation. Men-tal retardation (defined as FSIQ <70 or >-2SD below the mean) was found in 45%. In the

* majority of them, the mental retardation wasT- ~ mild (38%) and only two patients had moder-

ate mental retardation. Severe mental retarda-tion seems to be rare in VCFS. Only one childwith a familial deletion and cerebellar hypopla-sia (patient 23) was severely retarded. In theirinitial description of the syndrome Shprintzenet all recognised the presence of learningdisabilities in all patients. Since then, learning

} difficulties have been reported in 82% 17 toIII_l__ 4 4 100%'8 of the patients with VCFS. Mental

retardation (not specifically defined) seems tobe present in 40%'9 to 46%.'8 In the present

I I study, eight patients were initially referred forWit Som Anx Soc Tho Att Del Agg diagnosis because of developmental delay. This

Syndromes (CBCL) could have introduced a bias in the study.Behavioural profile in VCFS (CBCL 4-18). X However, we found no difference in FSIQ

it=withdrawn, Som=somatic complaints, between this group of patients and the remain-ixious, Soc=social problems, Tho=thought problems, ing patients. Our findings are thereforeention problems, Del=delinquent behaviour,gressive behaviour. Y axis: average T scores for the representative of VCFS, irrespective of their)up for the different syndromes. *Statistically referral pattern. Also, in this series, 37tnt higher score (Scheffi's test post hoc). consecutively diagnosed patients were exam-

ined, thus eliminating a further possible bias.The present study also confirms a wide vari-

ition problems" (average T score of 64), ability in intelligence in VCFS patients. UntilVithdrawn" (average T score of 58). Post now there have been no good explanations foratistical test (Scheffe's test) shows that this variability in intelligence (for example, noisters "Social problems" and "Attention correlation with the extent of the deletion).mis" score statistically significantly Also, we found no correlation between intelli-than the other clusters of problem gence and the presence or absence of a

iour, except the cluster "Withdrawn" (fig congenital heart defect. However, the inci-dence of mental retardation was found to be

the interpretation of the results, a much higher in the patients with a familial-tion was made between the normal/bor- deletion than in patients with a de novointelligent children (IQ >70, n= 12) and deletion. We found a statistically significantoup of children with mental retardation difference of 16.6 IQ points between the mean:70, n=7). This distinction was made FSIQ of the patients with a "familial" deletionse there are no norms available for the (mean FSIQ 63.2) and the mean FSIQ of theIly retarded children. patients with a "de novo" deletion (mean FSIQie group of normal/borderline intelligent 79.8). As far as we know, this has not beenn, three out of 12 (patients 13, 28, and reported in VCFS. This difference, however,d a total T score within the clinical range can possibly be explained in part by the lower53). In individual patients, "clinical" educational level of the affected parents thanon the syndromes (T score >70) were the unaffected parents. Indeed, parental IQfor "Attention problems" (n=3), "Social and socioeconomic status are major determin-ms" (n=3), "Thought problems" (n=1), ing factors of the IQ in their children, and thisWithdrawn" (n= 1). The same behav- was estimated here by their educational level.profile with "peaks" at "Attention prob- This is further supported by the two patients"Social problems", and "Withdrawn" with a familial deletion but a FSIQ of

[so found in the non-clinical group (T respectively 77 (patient 34) and 86 (patient)ut was less pronounced. This profile was 37): their unaffected parent had a highery found at the age of 5 years and we educational level compared to parents of otherno differences between boys and girls. familial cases (table 1). Except for these two;o found evidence for higher scores (but patients, the parent in familial cases, not

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carrying the deletion, had a lower SEScompared to parents of de novo cases, suggest-ing assortative mating. Associated cerebralmalformations could also be a possible expla-nation: in the present study, the severely men-tally retarded boy (patient 23) showed acerebral malformation, although Mitnick et af'did not find such a correlation.More studies are needed to confirm these

results and to determine the impact on intelli-gence of other associated malformations orfactors, such as hypoparathyroidism, parentalorigin of the deletion, or immune status.

Besides the distribution of intelligence, thepre,,ent study also provided data on the intelli-gence profile of these children. Analysis of theWechsler subscales showed a statistically sig-nificant difference between the average verbalIQ and average performance IQ.

Subtest analysis was not done because of thesmall number of children tested by theWISC-R (n= 1). In most children, however,specific cognitive deficits (that is, visuo-perceptual-spatial ability and planning ability)could be suspected from the profile of theWISC-R. These results indicate that childrenwith VCFS possibly might have a higher riskfor developing problems in the field ofvisuoperceptual-spatial abilities and of execu-tive functioning. This needs further investiga-tion in a larger patient group, however. We pre-fer to refer to learning disabilities only in thegroup of children who are not mentallyretarded (FSIQ >70). The term "learningdisabilities" includes the following two basicassumptions: (1) the learning problem is theresult of the inadequate functioning of one ormore cognitive skills in the presence of intactintelligence (specificity); (2) there is a discrep-ancy between IQ and achievement. We have theimpression that the learning disabilities ofVCFS children show similarities with thelearning disabilities of girls with Turnersyndrome. Typically, visuospatial or spatial-perceptual abilities or both are impaired inpatients with Turner syndrome.1'14 However, itis clear that more studies are needed to definethe type of learning disabilities in VCFS andanswer questions regarding, for instance, visualand tactile attention of children with VCFS,differences between short term and long termmemory, etc.Very few data on the intelligence of children

with VCFS have been reported so far. In astudy by Golding-Kushner et al,4 17 childrenwith VCFS received a psychometric intelli-gence assessment. The 4 year olds obtainedmean IQs of 87 on the mainly verbal Stanford-Binet and 84 on the Leiter InternationalPerformance test. The 8 year olds obtained amean WISC-R verbal IQ of 76 and a meanperformance IQ of 79. The 13 year oldsobtained a verbal IQ of 79 and a meanperformance IQ of 70. Meaningful compari-sons between the scores of the younger groupand the two older groups could not be made, asthe different tests may well assess differentabilities.A second topic of interest in the present

study was the behaviour and the social compe-

tence of children and adolescents with VCFS.In the group of young children aged between 2and 3 years, somatic complaints ("constipa-tion" and "eats poorly") and (social) with-drawal were often reported. The finding ofconstipation in many patients has not beenreported before. This might suggest an abnor-mal motility of the large intestine. Severalcharacteristics ofVCFS are most likely relatedto an abnormal differentiation or migration ofcranial neural crest cells. The caudal neuralcrest has a major role in Hirschsprung'sdisease, characterised by an abnormal motilityof the large intestine. It cannot be not excludedthat minor disturbances of the caudal neuralcrest also occur in VCFS, leading to poorcolonic motility and constipation. Alterna-tively, the constipation might be related to thepoor muscle tone found in most children withVCFS at a young age.

In the group of older normal/borderlineintelligent children, three out of 12 childrenhad a total T score within the clinical range.Clinical scores on the syndromes in individualpatients were found on "Attention problems","Social problems", "Thought problems", and"Withdrawn". The same behavioural profilebut less pronounced was also found in patientswith non-clinical scores. We found no differ-ences between boys and girls, and this profilewas already present at the age of 5 years.

In the group of mentally retarded children,two out of seven children had a total T scorewithin the clinical range. Clinical scores on thesyndromes in individual patients were found on"Social problems" and on "Attention prob-lems". We conclude therefore that children andadolescents with VCFS have social problemson one hand (most of the internalised type,withdrawal, social problems) and problemswith attention/concentration already present ata young age on the other hand. So, children andadolescents with VCFS show extremes in theirbehaviour (withdrawn and shy on one hand,impulsive and disinhibited on the other hand).These findings are in accordance with the find-ings of Golding-Kushner et al.4 who assessedbehaviour and personality by a series ofinformal tests, interview, and parental history.The social withdrawal in children and adoles-cents with VCFS might result at least partlyfrom their impaired ability to communicatewith others. It might also be that neuropsycho-logical deficits (visual-perceptual impairments,problems with new situations) contribute totheir poorer social interaction skills. An impor-tant question is whether a pharyngoplasty andearly speech therapy can improve speech andthus self-confidence.

In addition to social and attention problems,our data also point to higher scores on theanxiety/depression syndrome in the older chil-dren ( 1 years and older). Adolescent and adultpatients with VCFS are at risk for developingpsychiatric disorders including schizophreniaand depression.'9 The most common symp-toms described in these reports are those asso-ciated with depression and anxiety disordersand include disturbed mood, severe vegetativesymptoms, disturbed appetite, fatigue, and low

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self-esteem, as well as poor concentration anddecision making ability.'9 Therefore, the find-ing in this study of higher levels on thedepression/anxiety scale in the older group is ofinterest, since this could be a first sign of devel-oping psychopathology. Further prospectivestudies are needed to address this question.To summarise, the present study showed that

the incidence of mental retardation is muchhigher in the familial than in the de novo group.Intelligence is not correlated with the presenceor absence of a heart defect. Significantlyhigher verbal IQs than lower performance IQs(probably related to deficits in visuospatial-perceptual functioning) were found. Problemsin social-emotional functioning and attentionwere found, and further studies are needed toassess the predictive value concerning theirpsychiatric status as adults. Longitudinal dataand studies with control groups (children witha cleft palate or heart defect, children withlearning disabilities, children with non-verballearning disabilities) are needed to confirmthese results and to show those deficits that arespecific for VCFS. This will allow us to providean accurate prognosis and appropriate inter-vention for VCFS children.

The authors wish to thank Dr Peter J Scambler for his kind giftof probe D0832, and all the families for their cooperation andsupport. We would like to express our gratitude to Lut Polleunisand Reinhilde Thoelen for their excellent technical assistance,and Rita Logist for helping in preparing the manuscript.

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2 Scambler PJ, Kelly D, Lindsay E, et al. Velo-cardio-facialsyndrome associated with chromosome 22 deletionsencompassing the DiGeorge locus. Lancet 1992;339: 1138-41.

3 Motzkin B, Marion R, Goldberg R, et al. Variablephenotypes in velocardiofacial syndrome with chromo-somal deletion. 7 Pediatr 1993;123:406-10.

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5 Devriendt K, Eyskens B, Swillen A, et al. The incidence of adeletion in chromosome 22ql1 in sporadic and familialconotruncal heart disease. EurJ7Pediatr 1996;155:721.

6 Wadey R, Daw S, Wickremasinghe A, et al. Isolation of anew marker and conserved sequences close to theDiGeorge syndrome marker HP500 (D22S134). J MedGenet 1993;30:818-22.

7 Van der Meulen BF, Smrkovsky M. Bayley ontwikkelingss-chalen (BOS 2-30). Lisse: Swets & Zeitlinger, 1983.

8 McCarthy D. Manual for the McCarthy scales of children'sabilities. London: The Psychological Corporation, Har-court Brace Jovanovich, 1972.

9 Van der Meulen BF, Smrkovsky M. McCarthy On-twikkelingsschalen (MOS 2 112 - 8 112). Lisse: Swets & Zei-tlinger, 1986.

10 Snijders JT, Snijders-Oomen M. Niet-verbale intelligentie-schaal Revised (SON-R 2 112-7). Groningen: Tjeenk-Willing, 1985.

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