Alternative titles; symbols
ORPHA: 2990; DO: 0081322;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17p13.1 | Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B | 618469 | Autosomal recessive | 3 | MYH3 | 160720 |
A number sign (#) is used with this entry because of evidence that contractures, pterygia, and spondylocarpotarsal fusion syndrome-1B (CPSFS1B) is caused by compound heterozygous mutation in the MYH3 gene (160720) on chromosome 17p13.
Contractures, pterygia, and spondylocarpotarsal fusion syndrome-1B (CPSFS1B) 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 spondylocarpotarsal fusion syndrome (CPSFS1A; 178110) is caused by heterozygous mutation in the MYH3 gene.
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.
The transmission pattern of CPSFS1B in the families reported by Cameron-Christie et al. (2018) was consistent with autosomal recessive inheritance.
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.
Cameron-Christie, S. R., Wells, C. F., Simon, M., Wessels, M., Tang, C. Z. N., Wei, W., Takei, R., Aarts-Tesselaar, C., Sandaradura, S., Sillence, D. O., Cordier, M.-P,, Veenstra-Knol, H. E., Cassina, M., Ludkig, K., Trevission, E., Bahlo, M., Markie, D. M., Jenkins, Z. A., Robertson, S. P. Recessive spondylocarpotarsal synostosis syndrome due to compound heterozygosity for variants in MYH3. Am. J. Hum. Genet. 102: 1115-1125, 2018. Note: Erratum: Am. J. Hum. Genet. 105: 669 only, 2019. [PubMed: 29805041] [Full Text: https://doi.org/10.1016/j.ajhg.2018.04.008]