Clin Genet 2000: 58: 84–85Printed in Ireland. All rights reser6ed

Letter to the Editor

Polydactyly in 22q11 syndrome: should it betaken into account?

To the Editor:2q11 deletion is associated with multiple congenitalanomalies, including conotruncal heart defects, hy-poplasia of the parathyroid gland and thymus,immunodeficiency, and facial dysmorphism (1, 2).There are only a few reports of skeletal malforma-tions in individuals with a deletion of 22q11, pri-marily hand abnormalities (3–5). Here we report ona caucasian male with 22q11 monosomy and anextra digit. The second child of healthy, unrelatedparents was born at term after an uneventful preg-nancy by normal spontaneous delivery in a smallclinic. The newborn had a birth weight of 2930 g.Apgar scores 9 and 10 were recorded at 1 and 5 min,respectively. Ten hours after birth, the patient pre-sented with grunting and progressive cyanosis andwas immediately transferred to our hospital inten-sive neonatal care unit. A systolic heart murmur ofgrade III/IV was discovered, with marked decreaseof pulses in the femoral arteries. Cardiologic assess-ment by echocardiography disclosed a type B inter-rupted aortic arch, a ventricular septal defect, apatent ductus arteriosus, and an abnormal origin ofthe left subclavian artery, requiring ventilatory andinotropic support. Serum calcium was low (1.3mg/dl; normal range, 6–10.4) and phosphorus lev-els were increased to 10.7 mg/dl (normal range,2.5–4.5). He had postaxial polydactyly of the lefthand. No polydactyly was present in other familymembers. Family history was only relevant con-cerning a maternal aunt with hypocalcemia. Onphysical examination, an abnormal facial appear-ance was noted (Fig. 1). Chest X-ray film failed toshow a thymic shadow. Microdeletion detectionwas performed by fluorescence in situ hybridization(FISH). Only one signal was obtained using theD22S75 DiGeorge chromosome region probe, andtwo signals using the control probe D22S39 (Oncor,Inc., Gaithersburg, MD, USA). At the age of 3days, the patient underwent a successful cardiacrepair. The supernumerary finger was excised, andthe histological examination confirmed an extra

digit. The first immunological studies showed aquantitative defect of CD3+ T cells (28% of totallymphocytes, 301 cells/ml) and decreased CD4/CD8ratio, with normal lymphoproliferative response toT and B cell mitogens. Spontaneous T cell reconsti-tution was seen after 10 months of follow-up. Thepatient is currently alive and asymptomatic.

In the large series of patients analysed by Ming,skeletal anomalies have been reported in up to 36%of the patients with 22q11 deletions studied. Ofthese, 6% had upper limb abnormalities, 15% in thelower limbs, 17% supernumerary ribs, and 11% a‘butterfly’ vertebral body (4). Our case providesfurther evidence of the association between 22q11deletion and postaxial polydactyly. The EurofetusStudy recently evaluated the accuracy of the antena-tal detection of malformations at a level 2 ultra-sonographic examination and reported a sensitivityto detect polydactyly of 9.5% (6). The diagnosis oflimb malformation can be established around the12th week of gestational age; its association with22q11 deletion could help with the prenatal diagno-sis of this syndrome.

Congenital heart defects, specifically conotruncalcardiac malformations, constitute the most com-mon cause of morbidity and mortality in thesepatients (1, 6, 7). The question now arises whetherdetection of skeletal anomalies such as polydactyly,without a family history of such malformation,indicates that there should be a more careful mon-itoring of the pregnancy. Colour and pulsedDoppler ultrasonography could be performed in thesecond and third trimesters of gestation, whencardiac defects (i.e. interrupted aortic arch in 22q11deletions) are optimally detectable. Since the fre-quency of association of upper and lower limbabnormalities in patients with 22q11 deletion is 20%(4), it may be advisable to check these fetusescarefully for cardiac defects.

Approximately half of the deliveries in Spain takeplace in small or outlying clinics. An early diagnosisof cardiac defects is particularly relevant in order tobring attention to the child’s risk of developing the

84

Letter to the Editor

Fig. 1. Facial dysmorphic features at the age of 4 months: noteocular hypertelorism, anteverted nostrils, low-set ears withnotch on the left ear, and mandibular hypoplasia (with in-tegrity of the palate).

Eduardo Fernandez-CruzRicardo P Fernandez-Pacheco

Juana Gil

References

1. Hong R. The DiGeorge Anomaly (Catch 22, DiGeorge/Ve-locardiofacial Syndrome). Sem Hematol 1998: 35 (4): 282–290.

2. Markert ML, Hummell DS, Rosenblatt HM et al. CompleteDiGeorge syndrome: persistence of profound immunodefi-ciency. J Pediatr 1998: 132: 15–21.

3. Cormier-Daire V, Iserin L, Theophile D et al. Upper limbmalformations in DiGeorge syndrome. Am J Med Gen1995: 56: 39–41.

4. Ming JE, McDonnald-McGinn DM, Megerian TE etal. Skeletal anomalies and deformities in patientswith deletions of 22q11. Am J Med Gen 1997: 72: 210–215.

5. Fryer A. Monocygotic twins with 22q11 deletion and dis-cordant phenotypes. J Med Genet 1996: 33: 173.

6. The Eurofetus Study Group, Grandjean H, Larroque D,Levi S. The performance of routine ultrasonographicscreening of pregnancies in the Eurofetus Study. Am JObstet Gynecol 1999: 181 (2): 446–454.

7. Fokstuen S, Arbenz U, Artan S, Dutly F, Bauersfeld U,Brecevic L, Fasnacht M, Rothlisberger B, Schinzel A.22q11.2 deletions in a series of patients with non-selectivecongenital heart defects: incidence, type of defects andparental origin. Clin Genet 1998: 53: 63–69.

Correspondence :Dr Juana GilServicio de InmunologıaHospital General Universitario Gregorio MaranonCalle Doctor Esquerdo 4628007 MadridSpainTel.: +34-91-5868461Fax: +34-91-5868018E-mail: juanagil@maptel.es

medical problems associated with the syndromeafter birth (7). Thus planning the delivery at atertiary care centre – where immediate advancedneonatal care can be provided – is paramount.

AcknowledgementsWe thank Consuelo Pedras and Ana Hernandez for theirexcellent technical assistance, and Jane Kinnear for thefinal revision of the manuscript.

Sil6ia Sanchez-RamonJoaquın Bartolome

Manuel Sanchez-LunaM Luisa Franco

Marıa Orera

85