Contractures, Pterygia, And Variable Skeletal Fusions Syndrome 1b

A number sign (#) is used with this entry because of evidence that contractures, pterygia, and variable skeletal fusions syndrome-1B (CPSKF1B) is caused by compound heterozygous mutation in the MYH3 gene (160720) on chromosome 17p13.

Description

Contractures, pterygia, and variable skeletal fusions syndrome-1B (CPSKF1B) is characterized by contractures of proximal and distal joints, pterygia involving the neck, elbows, fingers, and/or knees, and variable vertebral, carpal, and tarsal fusions. Inter- and intrafamilial variability has been observed (Cameron-Christie et al., 2018).

An autosomal dominant form of contractures, pterygia, and variable skeletal fusions syndrome (CPSKF1A; 178110) is caused by heterozygous mutation in the MYH3 gene.

Clinical Features

Cameron-Christie et al. (2018) reported 6 patients from 4 families who were compound heterozygous for mutations in the MYH3 gene. Contractures were a consistent finding, affecting variable joints including the neck, shoulders, elbows, fingers, hips, and knees. In addition, all of the patients exhibited vertebral fusions and scoliosis, and most also showed carpal/tarsal fusions as well as webbing involving the neck, elbows, fingers, and/or knees. Other features included facial dysmorphism, short neck, and absent finger flexion creases.

Molecular Genetics

From a cohort of 16 patients with multiple contractures and pterygia as well as vertebral fusions and variable carpal and/or tarsal fusions, who were known to be negative for mutation in the FLNB gene (603381), Cameron-Christie et al. (2018) identified 6 patients from 4 families who were compound heterozygous for mutations in the MYH3 gene (see, e.g., 160720.0017-160720.0020). The second mutation in all patients was a noncoding variant at a splice donor site flanking a noncoding exon in the 5-prime UTR of MYH3 (160720.0020), which the authors noted would not be detected by most clinical exome-capture programs.