Studies of Malformation Syndromes XXVA

Abstract

The statistical analysis of phenotypic data available on 180 cases of the Brachmann-de Lange syndrome (BDLS), (161 previously published, 19 personally studied) documented the incomplete nature of most case reports, and the fact that investigators are more likely to mention abnormal traits than normal traits in their reports; it did not uncover evidence of (etiologically pertinent) heterogeneity of the BDL phenotype. The finding of a C-autosomal ring in one of our patients and the available genetic and cytogenetic data are discussed in the context of the hypothesis that the BDLS is recessively inherited and that the homozygous state of this incompletely recessive gene predisposes to early zygotic chromosome breakage and/or chromosome loss which is lethal in most cases. The hypothesis of autosomal recessive inheritance is further strengthened by the discovery of a new BDL case (PM) at Central Wisconsin Colony in Madison (courtesy Dr. E. G. Kaveggia); this 35-year-old woman was the product of an uncle/niece marriage.

Cornelia de Lange syndrome in a mother and daughter

“…Extensive chromosome studies have been done and all, including more recent ones with prometaphase banding, have revealed normal karyotypes except for a few cases (Beck & Mikkelsen 1981, Merikangas et al 1977, McArthur & Edwards 1967, McIntire & Eisen 1965, Mot1 & Opitz 1971, Ptacek et al 1963. The abnormal karyotypes exhibited a wide variety of abnormalities but no consistent chromosomal aberration has been identified (Falek et al 1966, Motl & Opitz 1971, Noe & Hammond 1967, Sciorra et al 1979, Wilson et al 1978.…”

“…Most of the reported cases of the syndrome have been sporadic but there have been reports of monozygotic twins concordant for the syndrome (Watson 1979) and a few reports of families with several affected siblings (Beck 1974, Opitz et al 1971) that suggest it is familial. In 1969, Pashayan et al estimated the empirical risk of recurrence of the syndrome, once a sporadic case has appeared in a family, as 2 to 5%.…”

“…In 1969, Pashayan et al estimated the empirical risk of recurrence of the syndrome, once a sporadic case has appeared in a family, as 2 to 5%. Various authors have raised the possibility of auto-soma1 dominant or recessive inheritance (Motl & Opitz 1971, Pashayan et al 1969, Ptacek et al 1963.…”

“…The syndrome's major features are growth failure, mental retardation, microcephaly, characteristic facial features, hirsutism and skeletal abnormalities. A few reports in the literature have described families with several affected siblings (Beck 1974, Opitz et al 1971, raising the possibility of a single gene mode of inheritance. Chromosome analyses have mostly been normal, and the abnormalities found have not been consistent.…”