The Brachmann‐de Lange syndrome in two siblings of normal parents

Abstract

In this report we describe two male siblings with typical Brachmann‐de Lange syndrome. Both presented a severe form of this MCA syndrome, and died at the age of 3 months and 3 weeks, respectively. Family history was completely negative, parents were normal, and prometaphase chromosome studies failed to reveal a chromosomal basis for this unique malformation syndrome.

On the variable expression of the Brachmann‐de Lange syndrome

“…In this respect recurrence in sibs could be explained by germ cell mosaicism, as is well known in other autosomal dominant conditions, e.g. achondroplasia (Frijns et al 1983).…”

“…Most cases occur sporadically in an otherwise normal family, but familial occurrence of BDLS has repeatedly been reported. At least three instances of recurrence in sibs with apparently healthy parents have been described, suggesting autosomal recessive inheritance (Lieber et al 1973, Frijns et al 1987, Naguib et al 1987.…”

“…But there were no children with reduction deformities of forearms or gross internal anomalies. The sib pairs (Lieber et al 1973, Frijns et al 1987, Naguib et al 1987 with BDLS presented a severe form of BDLS with upper limb anomalies, severe growth and mental retardation, and frequently early death. The clinical spectrum of BDLS appears to be wide.…”

“…Boys and girls are equally affected. Although most cases occur sporadically in an otherwise normal family, the possibility of both autosomal recessive and autosomal dominant inheritance has been raised by several authors (Kumar et al 1985, Leavitt et al 1985, Robinson et al 1985, Bankier et al 1986, Frijns et al 1987.…”

Germline mosaicism in cornelia de lange syndrome: Dilemmas and risk figures

“…Therefore, in the authors' database, germline mosaicism ranges from a conservative 3.4% (12 families out of 351 with confirmed proband mutations) up to 5.4% (19 out of 351, including seven families with unknown mutations in the affected probands) [Slavin et al, ]. In keeping with these findings, Slavin et al [] state that the previous reported recurrence rate of 1.5% due to germline mosaicism, based on “various reported cases of apparently unaffected parents who had two or more children affected,” could constitute an under‐representation of the real situation [Beratis et al, ; Lieber et al, ; Naguib et al, ; Fryns et al, ; Jackson et al, ; Krajewska‐Walasek et al, ].…”