Objective: To update the phenotype, cause, mode of inheritance, and certainty of the diagnosis of Brachmann-de Lange syndrome.
Design: Case series with comparative review of pertinent literature.
Setting: A tertiary university-based pediatric genetic clinic.
Participants: All 37 children with Brachmann-de Lange syndrome examined between January 1982 and December 1992.
Intervention: None.
Main results: The syndrome was previously undiagnosed in 33 of the patients. Thirty-one were white, four were Hispanic, and two were African-American. In 22 of 32 patients, intrauterine growth had been retarded; in 32 of 37 subjects, height was below the National Center for Health Statistics fifth percentile and growth velocity was less than the 50th percentile in those with serial 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), seizures (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 variation makes them difficult to diagnose. Two patients were half first cousins; their parents (who were half siblings) had minor manifestations of Brachmann-de Lange syndrome, including hypertrichosis and developmental delay, suggesting possible autosomal dominant inheritance in this family.
Conclusions: The dysmorphic abnormalities associated with Brachmann-de Lange syndrome may be expanded to include cleft palate, nuchal webbing, and hypospadias, while the presence of seizures and hypopituitarism extend the functional abnormalities found in these patients. Most cases are sporadic, and in the absence of laboratory biomarkers for Brachmann-de Lange syndrome, the certainty of the diagnosis is high but not 100%. Submicroscopic deletion 3q25-3qter or uniparental disomy remains as a plausible cause of the syndrome.