BRACHMANN-DELANGE-SYNDROME - 1994 UPDATE

Objective: To update the phenotype, cause, mode of inheritance, and ce rtainty of the diagnosis of Brachmann-de Lange syndrome. Design: Case series with comparative review of pertinent literature. Setting: A ter tiary university-based pediatric genetic clinic. Participants: All 37 children with Brachmann-de Lange syndrome examined between January 198 2 and December 1992. Intervention: None. Main Results: The syndrome wa s previously undiagnosed in 33 of the patients. Thirty-one were white, four were Hispanic, and two were African-American. In 22 of 32 patien ts, intrauterine growth had been retarded; in 32 of 37 subjects, heigh t was below the National Center for Health Statistics fifth percentile and growth velocity was less than the 50th percentile in those with s erial measurements. Compared with reference texts and reported studies of Brachmann-de Lange syndrome, the incidences of cleft palate (eight of 37), hypospadias (six of 18), nuchal webbing (four of 37), seizure s (14 of 37), and hypopituitarism (four of 13) in the studied patients were increased. Standard karyotypes were obtained in 36 patients; all were normal. Familial cases are infrequent, and intrafamilial variati on makes them difficult to diagnose. Two patients were half first cous ins; their parents (who were half siblings) had minor manifestations o f Brachmann-de Lange syndrome, including hypertrichosis and developmen tal delay, suggesting possible autosomal dominant inheritance in this family. Conclusions: The dysmorphic abnormalities associated with Brac hmann-de Lange syndrome may be expanded to include cleft palate, nucha l webbing, and hypospadias, while the presence of seizures and hypopit uitarism extend the functional abnormalities found in these patients. Most cases are sporadic, and in the absence of laboratory biomarkers f or Brachmann-de Lange syndrome, the certainty of the diagnosis is high but not 100%. Submicroscopic deletion 3q25-3qter or uniparental disom y remains as a plausible cause of the syndrome.