33 De Lange Syndrome
Cornelia De Lange syndrome, Brachmann-De Lange syndrome
Prenatal/postnatal growth retardation, microbrachy- cephaly, synophrys, long eyelashes, hand and limb anomalies, mental retardation
Frequency: 1 in 30,000 births.
Genetics
Autosomal dominant (OMIM 122470); most cases sporadic; caused by mutations in NIPBL gene, mapped to chromosome 5q13.1.
Clinical Features
• Prenatal growth retardation, low birth weight, short stature
• Mental retardation
• Hirsutism, low anterior and posterior hairline
• Microcephaly, brachycephaly
• Long eyelashes, synophrys (confluent eyebrows)
• Depressed nasal bridge, anteverted nostrils
• Long philtrum, thin upper lip, downturned lips
• Small, widely spaced teeth
• Micrognathia
• Low-set ears
• Cleft palate
• Small hands and feet, tapering fingers, absence or deformity of limbs, mainly upper limbs (pho- comelia, oligodactyly)
• Limitation of large joint motion, flexion contrac- ture of elbows
• Congenital heart defects, diaphragmatic defects, genitourinary system defects
Differential Diagnosis
• Duplication 3q2 syndrome
• Fetal alcohol syndrome
• Coffin-Siris syndrome
• Gorlin-Chaudhry-Moss syndrome
Radiographic Features Skull
• Microbrachycephaly
• Choanal atresia
• Spurs of the mandible
• Teeth anomalies (delayed eruption, microdontia) Limbs
• Shortening of the long bones of upper limbs
• Severe upper limb malformations in 25%, uni- or bilateral (micromelia, phocomelia, hemimelia)
• Radial head dysplasia and dorsal dislocation (80%) Hands and Feet
• Small hands and feet
• Oligodactyly, syndactyly, clinodactyly of 5th fin- gers
• Proximally placed thumbs (70%)
• Hypoplasia of the 1st metacarpal and middle pha- lanx of the 2nd and 5th fingers
• Hypoplasia of the 3rd through 5th metatarsals
• Kirner deformity Generalized Bone Defects
• Retarded skeletal age Pelvis
• Flat acetabular angles
• Aseptic necrosis of the femoral head
• Coxa valga Chest
• Abnormal configuration of the thoracic cage (wide upper portion, short sternum, advanced development of sternal ossification centers)
• Thin ribs
De Lange Syndrome 674
Bibliography
Allanson JE, Hennekam RCM, Ireland M. De Lange syndrome:
subjective and objective comparison of the classical and mild phenotypes. J Med Genet 1997; 34: 645–50
Feingold M, Lin AE. Familial Brachmann-de Lange syndrome:
further evidence for autosomal dominant inheritance and review of the literature. Am J Med Genet 1993; 47: 1064–7 Filippi G. The de Lange syndrome: report of 15 cases. Clin
Genet 1989; 35: 343–63
Ireland M, Donnai D, Burn J. Brachmann-de Lange syndrome:
delineation of the clinical phenotype. Am J Med Genet 1993; 47: 959–64
Jackson L, Kline AD, Barr MA, Kock S. De Lange syndrome: a clinical review of 310 individuals. Am J Med Genet 1993; 47:
940–6
Krantz ID, McCallum J, DeScipio C, Kaur M, Gillis LA,Yaeger D, Jukofsky L, Wasserman N, Bottani A, Morris CA, Nowaczyk MJ, Toriello H, Bamshad MJ, Carey JC, Rappaport E, Kawauchi S, Lander AD, Calof AL, Li HH, Devoto M, Jackson LG. Cornelia de Lange Syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nat Genet 2004; 36: 631–5 Opitz JM. The Brachmann-de Lange syndrome. Am J Med
Genet 1985; 22: 89–102
Raddock SR, Lachman RS, Stoppenhagen CC, Carey JC, Ireland M, Moeschler JB, Cunniff C, Graham JM. Radiological fea- tures in Brachmann-de Lange syndrome. Am J Med Genet 1993; 47: 1006–13
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D
Fig. 33.1. Patient 1, newborn.
Growth retardation, hirsutism, low anterior hairline, long eye- lashes, synophrys, long philtrum, micrognathia, absence deformity of distal upper limbs, flexion con- tracture at the elbows
