Congenital Heart Defects And Skeletal Malformations Syndrome

A number sign (#) is used with this entry because of evidence that congenital heart defects and skeletal malformations syndrome(CHDSKM) is caused by heterozygous mutation in the ABL1 gene (189980) on chromosome 9q34.

Description

Congenital heart defects and skeletal malformations syndrome (CHDSKM) is characterized by atrial and ventricular septal defects, with aortic root dilation in adulthood. Skeletal defects are variable and include pectus excavatum, scoliosis, and finger contractures, and some patient exhibit joint laxity. Failure to thrive is observed during infancy and early childhood (Wang et al., 2017).

Clinical Features

Wang et al. (2017) studied affected individuals from 4 unrelated families who exhibited dysmorphic facial features, congenital heart disease, skeletal abnormalities, joint problems, failure to thrive, gastrointestinal problems, and male genital anomalies. In younger children, dysmorphic features included broad forehead, small nose, deep-set eyes, and small chin, whereas in older patients, the face appeared elongated, with a narrow maxilla, long and narrow nose, and pointed chin. Common skeletal abnormalities included pectus excavatum, scoliosis, finger contractures, and hindfoot deformity. Congenital heart defects included atrial and ventricular septal defects, and in older patients, aortic root dilation. Joint laxity was present in 3 patients.

Molecular Genetics

In the probands from 4 unrelated families with congenital heart defects and skeletal malformations, Wang et al. (2017) performed exome sequencing and identified heterozygosity for missense mutations in the ABL1 gene in all 4; 3 probands had a Y245C (189980.0007) mutation, and 1 proband had an A356T (189980.0008) mutation. The mutations segregated with disease in each family, and the Y245C variant was shown to have arisen de novo in 2 of the families.