Discordant, non-syndromic, congenital diaphragmatic defects in sibs.

Abstract

We report an Arab sibship of two brothers with non-syndromic, congenital diaphragmatic defects (CDD). The first had an extensive, left, Bochdalek-type hernia and the second hemidiaphragmatic agenesis; these were verified by surgical exploration and necropsy respectively. The parents are healthy second cousins. Other reported discordant cases of CDD are briefly reviewed. Con1genital diaphragmatic defects have been classified into (1) posterolateral (Bochdalek) hernia, (2) retrosternal (Morgagni) hernia, and (3) the rare extensive defects involving most or all of the hemidiaphragm (agenesis). They are generally considered to be one entity, that is, malformation or developmental defects with an incidence somewhere between 1 in 800 and 1 in 10 000.2-4 Makela5 reported the first family with affected sibs in 1916. Mertins,6 in 1952, was the first to suspect that CDD could occur in a familial aggregation. In Kuwait, we recently observed an Arab family with discordant, non-syndromic CDD in sibs. Case reports CASE 1 A male infant was born in 1984 after an uneventful, term pregnancy, weighing 3600 g. He was the second child of phenotypically normal, second cousin Jordanian parents. At birth he looked normal. His Apgar scores were 8 and 9 at one and five minutes. He rapidly developed severe respiratory distress and metabolic acidosis. An extensive, left sided diaphragmatic hernia was diagnosed clinically and by chest radiography. The diagnosis was verified by surgical exploration. The hernial sac contained the stomach, the intestines extending to the splenic flexure, the spleen, the left lobe of the liver, and the left testis. It was repaired at the age of six hours. The baby died four hours later from cardiac arrest. The mother, when pregnant again, was given

Overview of epidemiology, genetics, birth defects, and chromosome abnormalities associated with CDH

“…[Butler and Claireaux, 1962; Welch and Cooke, 1962; Scott and Patterson, 1966; Passarge et al, 1968; ten Kate and Anders, 1970; Feingold, 1971; Harberg et al, 1976; Thomas et al, 1976; Crane, 1979; David et al, 1979; Pollack and Hall, 1979; Arad et al, 1980; Wolff, 1980; Gencik et al, 1982; Norio et al, 1984; Czeizel and Kovacs, 1985; Lipson and Williams, 1985; Toriello et al, 1985; Bocian et al, 1986; Toriello et al, 1986; Farag et al, 1989; Hitch et al, 1989; Carmi et al, 1990; Frey et al, 1991; Sripathi and Beasley, 1992; Narayan et al, 1993; Farag et al, 1994; Gibbs et al, 1997; Mitchell et al, 1997; Kufeji and Crabbe, 1999; Manouvrier‐Hanu et al, 2000]. As part of our own research over the last 5 years, we ascertained more than two dozen multiplex families in whom the diagnosis of a syndrome was not established.…”

Infants with Bochdalek diaphragmatic hernia: Sibling precurrence and monozygotic twin discordance in a hospital‐based malformation surveillance program

“…Multiplex families with CDH-Numerous multiplex families with either isolated or complex CDH have been published [Butler and Claireaux, 1962;Welch and Cooke, 1962;Scott and Patterson, 1966;Passarge et al, 1968;ten Kate and Anders, 1970;Feingold, 1971;Harberg et al, 1976;Thomas et al, 1976;Crane, 1979;David et al, 1979;Pollack and Hall, 1979;Arad et al, 1980;Wolff, 1980;Gencik et al, 1982;Norio et al, 1984;Czeizel and Kovacs, 1985;Lipson and Williams, 1985;Toriello et al, 1985Toriello et al, , 1986Bocian et al, 1986;Farag et al, 1989;Hitch et al, 1989;Carmi et al, 1990;Frey et al, 1991;Sripathi and Beasley, 1992;Narayan et al, 1993;Farag et al, 1994;Gibbs et al, 1997;Mitchell et al, 1997;Kufeji and Crabbe, 1999;Manouvrier-Hanu et al, 2000]. Several of these families are consanguinous, making it likely that a single mutant gene is responsible for their disorder [Arad et al, 1980;Norio et al, 1984;Farag et al, 1989Farag et al, , 1994, though multifactorial inheritance cannot be ruled out as an explanation for familial clustering.…”

“…Several of these families are consanguinous, making it likely that a single mutant gene is responsible for their disorder [Arad et al, 1980;Norio et al, 1984;Farag et al, 1989Farag et al, , 1994, though multifactorial inheritance cannot be ruled out as an explanation for familial clustering. The discovery of mutations in the interferon regulatory factor 6 gene (IRF6) as the cause of lip pit or van der Woude syndrome could be a model for identifying multifactorial genetic changes contributing to CDH.…”

Recurrence of diaphragmatic agenesis associated with multiple midline defects: Evidence for an autosomal gene regulating the midline

“…He reviewed the literature and found 4 other reports of families with 2 affected sibs born of normal parents and concluded that an autoso-ma1 recessive gene might be responsible, although no consanguinity could be documented for any family. As of 1992, there were at least 18 reports of familial agenesis of the diaphragm, some with a single other associated abnormality [Passarge et al, 1968;ten Kate and Anders, 1970;Feingold, 1971;Jensen and Altrogge, 1971;Daentl and Passarge, 1972;h a d et al, 1980;Wolff, 1980;Gencik et al, 1982;Bocian et al, 1983;Norio et al, 1984;Farag et al, 1989;Sripathi and Beasley, 19921. In 3 families, consanguinity was documented [ h a d et al, 1980;Norio et al, 1984;Farag et al, 19891 and remote consanguinity was suspected in another family [Daentl and Passarge, 19721.…”