INTRODUCTION

Cornelia de Lange syndrome (CdLS) (also known Brachmann de Lange syndrome) is a rare and well known genetic syndrome characterized by intrauterine growth retardation, typical facial features, microbrachycephaly, short stature, hirsutism and limb anomalies. Although almost any organ system can be affected, the neurodevelopmental, craniofacial, gastrointestinal, and musculoskeletal systems are the most commonly involved (1,4). Facial features and typical extremity findings help to establish the diagnosis. The lower extremities are less involved than the upper extremities. The feet are often small and two-three syndactyly of the toes occurs in over 80% of affected individuals (2, 3). Here we report on the case of a Cornelia de Lange syndrome with bilateral cleft feet and to our best knowledge this limb anomaly has not been reported before.

CASE REPORT

An 11-month-old boy was admitted to the hospital with fever, oliguria, and diarrhea. He was the first child of a first degree consanguineousIy married couple. He was born at 38 weeks with severe intrauterine growth retardation only weighing 1000 gram. He was hospitalized for one month in the neonatal intensive care unit. He had a cleft palate and lip operation when he was 4 months old. Initial examination revealed an acutely ill looking febrile (38.5 degrees Celsius) and mildly dehydrated infant with a weight of 4.9 kg., length of 50.0 cm and a head circumference of 37.0 cm. All these measurements were well below the 3rd percentile on relevant standardized charts. He was tachycardie and tachypneic. The cardiovascular, respiratory and abdominal examinations were normal. Additional physical examination findings included microcephaly, long curly eyelashes, arched eyebrows synophrys, operated cleft lip and palate, depressed nasal bridge, low set ears, facial-frontal hirsutism (Fig. 1). Testes were bilateral unpalpable. There was bilateral syndactyly between 3rd and 4th digits of the hands. Feet revealed deep extending cleft proximally, involving distal one third of feet with normal great toes and syndactyly of fourth and fifth toes on the right side (Fig. 2).

White blood cell count was 21000/mm^sup 3^, blood urea and Creatinin levels were high (135 mg/dl and 3.5 mg/dl), respectively. Serum Na level was also high (172 meq/L). The echocardiogram and renal ultrasonograpy were normal. Chromosomal analysis was done on peripheral blood lymphocytes according to conventional techniques. The analysis revealed a normal male karyotype (46, XY). The final diagnosis was Cornelia de Lange syndrome associated with bilateral cleft feet and prerenal acute renal failure.

DISCUSSION

Cornelia de Lange syndrome (CdLS) is a well described genetic disorder. Most cases of CdLS appear to be sporadic. Familial cases are rare and indicate autosomal dominant inheritance (6). CdLS is characterized by distinctive facial features, growth retardation (prenatal onset; <5th centile throughout life), hirsutism, and upper limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly. The lower extremities are less involved than the upper extremities. The feet are often small and two-three syndactyly of the toes occurs in over 80% of affected individuals (3). The review of radiologic manifestations of CdLS show that unusual radiologic manifestations found with CdLS are related primarily to the limb anomalies, and these are often asymmetric (2). The clinical phenotype of our patient is concordant with typical facial features and intrauterine growth retardation, short stature, microbrachycephaly, hirsutism.

Split-hand/split-foot malformation also known as ectrodactyly, is a congenital limb malformation, characterized by a deep median cleft of the hand and/or foot due to the absence of the central rays. This malformation may occur as an isolated entity or as part of a syndrome. Ectrodactyly is frequently seen in combination with other congenital anomalies. Such ectrodactyly syndromes may be caused by genetic factors or by exposure of the embryo to environmental factors (5). In The London Dysmorphology Database more than 50 syndromes and associations are distinguished (7). Split foot associated with CdLS was not reported. The association of bilateral split feet is a new finding in CdLS.

References:

1. AKDENIZ C., ODEMIS E., ERDEM A., CELEBI A:. Double outlet right ventricle and aortopulmonary window in a patient with Cornelia de Lange syndrome: a novel association. Genet. Couns., 2009, 20(2), 161-166.

2. BRADDOCK S.R., LACHMAN R.S., STOPPENHAGEN C.C., CAREY J.C., IRELAND M., MOESCHLER J.B., CUNNIFF C., GRAHAM J.M.: Radiological features in Brachmann-de Lange syndrome. Am. J. Med. Genet., 1993, 47(7), 1006-1013.

3. JACKSON L., KLINE A.D., BARR M.A., KOCH S.: de Lange syndrome: a clinical review of 310 individuals. Am. J Med. Genet., 1993, 47(7), 940-946.

4. KLINE A.D., KRANTZ I.D., SOMMER A., KLIEWER M., JACKSON L.G., FITZPATRICK D.R., LEVIN A.V., SELICORNI A.: Cornelia de Lange syndrome: clinical review, diagnostic and scoring systems, and anticipatory guidance. Am. J. Med Genet., 2007, 12, 1287-1296.

5. PASCAL H.G., DUlJF P.H., VAN BOKHOVEN H., BRUNNER H.G.: Pathogenesis of split-hand/splitfoot malformation. Hum. MoI Genet., 2003, 12, R51-R60.

6. RUSSELL K.L., MNG J.E., PATEL K., JUKOFSKY L., MAGNUSSON M., KRANTZ I.D.: Dominant paternal transmission of Cornelia de Lange syndrome: a new case and review of 25 previously reported familial recurrences. Am. J. Med. Genet., 2001, 104, 267-276.

7. WINTER R.M. AND BARAITSER M.: The London Dysmorphology Database. J. Med. Genet., 1987,24, 509-510.

Author affiliation:

BY D.G. DOGAN1, M. DOGAN2, M. ASLAN1 AND H. KARABIBER1

Author affiliation:

(1) Department of Pediatrics, Inönü University, Faculty of Medicine, Malatya, Turkey.

(2) Department of Radiology, Inönü University, Faculty of Medicine, Malatya, Turkey.

Author affiliation:

ADDRESS FOR CORRESPONDENCE:

Derya Gumus Dogan, MD

Department of Pediatrics

Inonu University School of Medicine

Turgut Ozal Medical Center

44315, Malatya, Turkey

Phone: +90 422 3410660; Fax: +90 422 3410660

E-mail: deryagumus@yahoo.com