X‐linked midline defects

Abstract

Opitz and Gilbert [Am J Med Genet 12:443-455, 1982] have postulated that the midline may be a kind of developmental field. Although developmental field defects (primary malformations) usually occur sporadically, in some instances they can be caused by a single gene mutation. We report on a family in which the occurrence of midline defects was consistent with X-linked inheritance. Anomalies present in the family include hydrocephalus, anencephaly, cleft lip, congenital heart defect, renal agenesis, and hypospadias.

Epidemiological analysis of the schisis association in the Spanish registry of congenital malformations

“…The differences between the number of cases with affected first-degree relatives observed by Czeizel [1981] and by us could well be due to differences in the genetic background of the Hungarian and Spanish populations. On the other hand, some of the cases with affected sibs observed by Czeizel [1981] could represent any of the X-linked recessive midline defects described after publication of his report [Toriello and Higgins, 1985;Martínez-Frías, 1994]. It is well-known that midline defects tend to cluster among themselves [Opitz and Gilbert, 1982;Khoury et al, 1989;Mathias et al, 1987;Martínez-Frías, 1994].…”

Congenital diaphragmatic defects and associated syndromes, malformations, and chromosome anomalies: A retrospective study of 60 patients and literature review

“…Diaphragmatic agenesis is relatively rare, occurring in ഛ1-6% of CDDs [Cunniff et al, 1990;Tibboel and Gaag, 1996], and its pathogenesis is also unknown. Although diaphragmatic agenesis may have a different pathogenesis than diaphragmatic hernias, and there have been familial cases in which only diaphragmatic agenesis is present [Norio et al, 1984;Toriello and Higgins, 1985;Bird et al, 1994a;Gibbs et al, 1997], both disorders may exist in the same sibship [Arad et al, 1980;Wolff 1980;Farag et al, 1994]. In the summary tables (Tables I-V), a distinction was not made between congenital diaphragmatic hernia and diaphragmatic agenesis, because many reports did not emphasize the difference.…”

“…Isolated CDDs have been considered to represent sporadic malformations with low recurrence risk, with familial cases representing ഛ2% [Tibboel and Gaag, 1996]. However, familial cases of CDDs have been described, with autosomal recessive [David et al, 1979;Arad et al, 1980;Mishalany and Gordo, 1986;Hitch et al, 1989;Harris et al, 1993;Bird et al, 1994a;Farag and Wilson, 1994;Gibbs et al, 1997], autosomal dominant [Crane, 1979;de Meeus et al, 1997], X-linked recessive [Crane, 1979;Toriello and Higgins, 1985;Martin et al, 1992], and X-linked dominant [Bird et al, 1994a;Parvari et al, 1994] inheritance. In some populations, multifactorial inheritance best explains the occurrence of CDDs [Crane, 1979;Wolff, 1980], and a recurrence risk of 2% has been estimated [Norio et al, 1984;Narayan et al, 1993].…”

Familial occurrence of agonadism and multiple internal malformations in phenotypically normal girls with 46,XY and 46,XX karyotypes, respectively: A new autosomal recessive syndrome

“…This indicates a "threshold defect" or an "all-or-none trait" of embryogenesis [Opitz, 19851. There is ample evidence that developmental field defects are always heterogeneous [Opitz and Gilbert, 1982;Opitz, 19851. However, in some instances, the midline defect may be the result of a single gene mutation [Toriello and Higgins, 1985;Baker et al, 1984;Opitz, 1985;Hingorani et al, 1991;Smith et al, 1992; this report].…”