Holt‐Oram syndrome: penetrance of the gene and lack of maternal effect

Abstract

Holt‐Oram syndrome is an autosomal dominant disorder with variable expression. From a review of published pedigree data and of a family reported here, we have found that penetrance is 100 % if appropriate studies, including wrist radiographs, are performed. There does not appear to be a significant maternal effect on the severity of expression in affected offspring.

Prenatal diagnosis of Holt‐Oram syndrome: Role of 3‐D ultrasonography

“…There are other conditions with both cardiovascular and upper limb defects apart from HOS, such chromosomal disorders like trisomy 13 and trisomy 18, some autosomal recessive disorders (e.g. Fanconi anemia), thrombocytopenia and absent radius (TAR) syndrome, and sporadic cases of VACTERL association (Gladstone and Sybert 1982). The normal platelet count and the absence of specific structural anomalies other than the cardiac defect in our case eliminated the possibility of TAR syndrome.…”

“…This upper limb and cardiovascular syndrome is an autosomal dominant disease with 100% penetrance, and has no significant maternal influence on the severity of the expression in the affected offspring (Gladstone & Sybert 1982). Molecular genetic studies have determined that mutations in the TBX‐5 (T‐box 5) gene on chromosome 12q24.1 are responsible for both the cardiac and skeletal phenotypic manifestations in this genetic disorder (Basson et al.…”

Holt‐Oram syndrome in four half‐siblings with unaffected parents: brief clinical report

“…This represents the first known example of the disorder being transmitted through an unaffected parent to his children. 1: is known that the penetrance of the syndrome is 100% (Gladstone & Sybert 1982), and the sporadic appearance of the syndrome is thought to represent new gene mutations which may account for up to 40% of affected individuals. It is unlikely that the four affected children described here represent new mutations.…”

Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis

“…Notice of abnormalities in cardiovascular system and in upper limbs needs to be differentiated with trisomy 13, 18 and others heart-hand syndromes, brachydactyly and long-thumb syndromes, disturbances connected with SALL4 gene mutations (Okihiro syndrome), Fanconi anemia, TAR (thrombocytopenia and absent radius) syndrome, some cases of VACTERL association or 22q11.2 deletion, 5q35.2-q35.3microduplications or embryopathies [17,18].…”