ORPHA: 319340; DO: 0050471;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17p13.1 | Carney complex variant | 608837 | 3 | MYH8 | 160741 |
A number sign (#) is used with this entry because Carney complex variant associated with distal arthrogryposis is caused by mutation in the MYH8 gene (160741).
For a phenotypic description of Carney complex, see (160980).
Veugelers et al. (2004) described a Caucasian Belgian family, originally reported by (Chaudron et al., 1992), with Carney complex variant and trismus-pseudocamptodactyly syndrome (158300). In 18 affected members of the family, they identified an arg674-to-gln substitution in the MYH8 gene (R674Q; 160741.0001). Penetrance of the disorder was complete, although expressivity was highly variable. Three affected family members had had cardiac myxomas, and all affected family members who were available for a complete examination had spotty skin pigmentation alone or in combination with cutaneous lesions. Most of the family members had distal arthrogryposis, including pseudocamptodactyly of the hands and feet, trismus, or both, which improved symptomatically with aging. Two family members had required palliative hand surgery, and 1 had had foot surgery.
Stratakis et al. (2004) argued that the syndrome described by Veugelers et al. (2004) was not in fact a variant of Carney complex. They stated that among more than 500 patients with the Carney complex in their database, there was none with trismus-pseudocamptodactyly syndrome. In an analysis of patients reported to have trismus-pseudocamptodactyly syndrome, they identified several with freckling. These patients appeared to have a familial disorder distinct from a simple Carney complex variant. Patients with trismus-pseudocamptodactyly syndrome had none of the lesions or endocrine syndromes typical of Carney complex. Trismus-pseudocamptodactyly syndrome with freckling may or may not be associated with familial myxomas and may or may not be caused by a single mutation of the MYH8 gene, but their own data led Stratakis et al. (2004) to conclude that this disorder is distinct from the Carney complex.
Toydemir et al. (2006) studied 4 trismus-pseudocamptodactyly pedigrees and identified the R674Q mutation in the MYH8 gene in 19 affected members, none of whom had multiple hyperpigmented macules or cardiac myxomas. The R674Q mutation was not found in 49 unrelated cases of Carney complex who were negative for mutation in the PRKAR1A gene (188830); Toydemir et al. (2006) concluded that R674Q rarely, if ever, causes Carney complex.
Chaudron, J. M., Jacques, J. M., Heller, F. R., Cheron, P., Luwaert, R. The myxoma syndrome: an unusual entity: a family study. Europ. Heart J. 13: 569-573, 1992. [PubMed: 1600999] [Full Text: https://doi.org/10.1093/oxfordjournals.eurheartj.a060216]
Stratakis, C. A., Bertherat, J., Carney, J. A. Mutation of perinatal myosin heavy chain. (Letter) New Eng. J. Med. 351: 2556 only, 2004. [PubMed: 15590965] [Full Text: https://doi.org/10.1056/NEJM200412093512420]
Toydemir, R. M., Chen, H., Proud, V. K., Martin, R., van Bokhoven, H., Hamel, B. C. J., Tuerlings, J. H., Stratakis, C. A., Jorde, L. B., Bamshad, M. J. Trismus-pseudocamptodactyly syndrome is caused by recurrent mutation of MYH8. Am. J. Med. Genet. 140A: 2387-2393, 2006. [PubMed: 17041932] [Full Text: https://doi.org/10.1002/ajmg.a.31495]
Veugelers, M., Bressan, M., McDermott, D. A., Weremowicz, S., Morton, C. C., Mabry, C. C., Lefaivre, J.-F., Zunamon, A., Destree, A., Chaudron, J.-M., Basson, C. T. Mutation of perinatal myosin heavy chain associated with a Carney complex variant. New Eng. J. Med. 351: 460-469, 2004. [PubMed: 15282353] [Full Text: https://doi.org/10.1056/NEJMoa040584]