Proximal symphalangism (SYM1) is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and conductive deafness (summary by Takahashi et al., 2001).
- Genetic Heterogeneity of Proximal Symphalangism ... Proximal symphalangism (SYM1) is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and conductive deafness (summary by Takahashi et al., 2001). - Genetic Heterogeneity of Proximal Symphalangism Another form of proximal symphalangism (SYM1B; 615298) is caused by mutation in the GDF5 gene (601146)
Cushing (1916) described a large American family in which many members had ankylosis of the proximal interphalangeal joints and assigned the designation symphalangism to the disorder. Fusion of carpal and tarsal bones is also a feature (see 186400, ... Cushing (1916) described a large American family in which many members had ankylosis of the proximal interphalangeal joints and assigned the designation symphalangism to the disorder. Fusion of carpal and tarsal bones is also a feature (see 186400, 186750). This trait was thought to enjoy the distinction of being traced through more generations than almost any other, having been identified in the first Earl of Shrewsbury who lived in the 15th century (Drinkwater, 1917). After a reexamination of the evidence, however, Elkington and Huntsman (1967) concluded that the Earl probably did not have symphalangism and that the mutation is of more recent origin in that kindred. In the family reported by Vesell (1960), mother and daughter had conductive deafness. The mother apparently had a new mutation. Strasburger et al. (1965) followed up on Cushing's family. Conductive deafness with early onset occurred sufficiently often in affected members of this large kindred to suggest that it is an effect of the same gene. Cremers et al. (1985) reemphasized the association of deafness, as pointed out by Gorlin et al. (1970), Spoendlin (1974), Baschek (1978), and others. Cremers et al. (1985) also published the first report on the histology of the stapes. Wildervanck et al. (1967) observed 2 accessory bones in the feet of multiple affected persons in 1 family. Attempts at surgical creation of interphalangeal joints had not been successful (Smith and Lipke, 1979). It is not certain whether the family reported by Kassner et al. (1976) had Cushing symphalangism or a distinct disorder. The changes in the proximal phalangeal joints were typical but one member also had metacarpophalangeal synostosis. Others had radial head dislocation and radiohumeral synostosis, which have been reported. Proximal symphalangism occurs with diastrophic dysplasia (222600). Symphalangism also occurs among the multiple digital anomalies of brachydactyly, type C (BDC; 113100). Spoendlin (1974) described a family in which members over several generations in a dominant, possibly autosomal, pedigree pattern showed fusion of tarsal and carpal bones. Several of the affected female members of the family also had deafness due to congenital ankylosis of the stapes. The family was of Italian origin. The foot and hand deformities were more severe in females also. No mention of short stature was made. The fusion of carpal and tarsal bones was similar to that seen in association with SYM1; deafness due to ankylosis of the stapes occurs in that condition also (Strasburger et al., 1965). In a child with symphalangism reported by Stephan (2006), complete fixation of all the ossicular articulations was found at surgery for correction of her deafness, and total reconstruction of the ossicular chain was necessary.
Gong et al. (1999) demonstrated 5 dominant NOG mutations in 5 unrelated families segregating proximal symphalangism and a de novo mutation in a patient with unaffected parents. They also found a dominant NOG mutation in a family segregating ... Gong et al. (1999) demonstrated 5 dominant NOG mutations in 5 unrelated families segregating proximal symphalangism and a de novo mutation in a patient with unaffected parents. They also found a dominant NOG mutation in a family segregating multiple synostoses syndrome (SYNS1; 186500); thus, SYM1 and SYNS1, both of which have multiple joint fusion as their principal feature, are allelic disorders. Gong et al. (1999) found that the mutation in the historic family with symphalangism studied by Cushing (1916), family 1 of Gong et al. (1999), was a tyr222-to-cys change in Noggin (602991.0001). Takahashi et al. (2001) identified 3 novel mutations in Japanese patients: a cys184-to-tyr mutation (602991.0009) in a sporadic case of symphalangism, a leu129-to-ter mutation (602991.0010) in a familial case of symphalangism, and a 1-bp frameshift mutation (602991.0011) in a family with multiple synostoses syndrome.