Thoracoabdominal Syndrome

Clinical Features

Carmi et al. (1990) suggested X-linked dominant inheritance for a previously undescribed malformation syndrome. The features were diaphragmatic and ventral hernias, hypoplastic lung, and cardiac anomalies such as transposition of the great vessels and patent ductus arteriosus (see 607411). Carmi et al. (1990) pointed out that another syndrome that combines defects of the abdominal wall and the diaphragm is the sporadic pentalogy of Cantrell (Cantrell et al., 1958). Although the abdominal wall defect, even in its severe form, was equally present in females and males, the diaphragmatic and lung anomalies were mostly confined to males. In 7 of 10 affected males, these anomalies were fatal. Cardiovascular abnormalities were not diagnosed in any living affected member of the family.

Carmi et al. (1990) described a family in which 4 male fetuses had cystic hygroma, cleft palate, omphalocele, or diaphragmatic hernia in various combinations.

Toriello and Higgins (1985) described a kindred in which 5 males in as many sibships, related through women, had 6 different defects which were all either midline or midline-associated malformations: hydrocephalus, anencephaly, cleft lip, congenital heart defect, renal agenesis, and hypospadias. Toriello and Higgins (1985) postulated that the midline may be a developmental field as suggested by Opitz and Gilbert (1982), and that a single gene mutation, in this instance on the X chromosome, had disrupted development.

Carmi and Boughman (1992) ascertained 5 cases of pentalogy of Cantrell through the Baltimore-Washington population-based study of infants with congenital cardiovascular malformations--a regional prevalence of 5.5 per 1 million liveborn infants. Three of the patients had cleft lip with or without cleft palate. Carmi and Boughman (1992) again proposed this as evidence of a ventral midline developmental field. At least 2 of the 5 patients were female (a third was stated to be female in Table I but by implication in the text to be male).

Martin et al. (1992) indicated that the association of sternal fusion defects with various cardiac, diaphragmatic, and anterior body wall defects represents a developmental field complex that includes the pentalogy of Cantrell and ectopia cordis. They presented a family in which 3 consecutively born brothers had extensive diaphragmatic defects; 2 of the brothers had the pentalogy of Cantrell and 1 of these 2 also had ectopia cordis.

Maas et al. (2009) described 2 women with Goltz-Gorlin syndrome, or focal dermal hypoplasia (FDH; 305600), who had 1 and 2 female fetuses, respectively, with a phenotype resembling either the limb-body wall complex (see 217100) or the pentalogy of Cantrell. Maas et al. (2009) suggested that some cases with the latter diagnoses may in fact be severely affected fetuses with Goltz-Gorlin syndrome.

Smigiel et al. (2011) reported an infant girl with genetically confirmed Goltz-Gorlin syndrome, with findings including sparse hair, clinical anophthalmia, clefting, bifid nose, irregular vermilion of both lips, asymmetric limb malformations, caudal appendage, linear aplastic skin defects, and unilateral hearing loss. The infant also had features of the pentalogy of Cantrell, including absent lower sternum, anterior diaphragmatic hernia, ectopia cordis, and omphalocele. Smigiel et al. (2011) stated that this was the third patient reported to have this combination of features.

Mapping

In studies of an extended family including 14 affected individuals, Carmi et al. (1993) obtained positive lod scores with markers in the region Xq22-q27. The maximum lod score was obtained for linkage with HPRT at Xq26.1; maximum lod = 5.11 at theta = 0.042. Additional results indicated that the TAS gene is located between the DXS425 and HPRT loci (Xq25-q26.1). Parvari et al. (1994) obtained a multilocus lod score of 12.4 when the linkage analysis utilized additional markers in Xq25-q26. Using microsatellite polymorphic markers, Parvari et al. (1996) narrowed the region of the TAS gene to an interval of about 2.5 Mb.