Radioulnar Synostosis With Amegakaryocytic Thrombocytopenia 1

A number sign (#) is used with this entry because of evidence that radioulnar synostosis with amegakaryocytic thrombocytopenia-1 (RUSAT1) is caused by heterozygous mutation in the HOXA11 gene (142958) on chromosome 7p15.

Description

Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is characterized by thrombocytopenia that progresses to pancytopenia, in association with congenital proximal fusion of the radius and ulna that results in extremely limited pronation and supination of the forearm (summary by Niihori et al., 2015).

Genetic Heterogeneity of Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia

Radioulnar synostosis with amegakaryocytic thrombocytopenia-2 (RUSAT2; 616738) is caused by heterozygous mutation in the MECOM gene (165215) on chromosome 3q26.

Clinical Features

Thompson and Nguyen (2000) observed 2 families with autosomal dominant inheritance of radioulnar synostosis (see 179300) in association with amegakaryocytic thrombocytopenia. The fathers and all affected children in both families (2 of 3 in 1 family and both children in the other) had the same skeletal defect, proximal fusion of the radius and ulna, resulting in extremely limited pronation and supination of the forearm. Three of the 4 children with radioulnar synostosis also had symptomatic thrombocytopenia, with bruising and bleeding problems since birth, necessitating correction by bone marrow or umbilical cord stem cell transplantation. The fathers had normal platelet counts and no history of bleeding or bruising.

Thompson et al. (2001) provided full clinical details on the 2 families with autosomal dominant radioulnar synostosis and amegakaryocytic thrombocytopenia. Their family 1 had 2 affected sisters in whom thrombocytopenia was treated successfully with bone marrow transplantation. The father had proximal radioulnar synostosis, bilateral clinodactyly of the fifth digits (present also on the right hand of the older sister), and webbed fingers, but no hematologic abnormality. Both sisters had hip dysplasia with dislocation. In their family 2, Thompson et al. (2001) observed an affected sister and brother. The father had radioulnar synostosis and bilateral fifth digit clinodactyly.

Inheritance

Thompson et al. (2001) reported 2 families with autosomal dominant inheritance of radioulnar synostosis and amegakaryocytic thrombocytopenia.

Molecular Genetics

In affected members of 2 families segregating radioulnar synostosis and amegakaryocytic thrombocytopenia, Thompson and Nguyen (2000) identified a heterozygous mutation in the HOXA11 gene (142958.0001).