Other entities represented in this entry:
SNOMEDCT: 702312009; ORPHA: 1412; DO: 0050789;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q22 | Tarsal-carpal coalition syndrome | 186570 | Autosomal dominant | 3 | NOG | 602991 |
A number sign (#) is used with this entry because of evidence that tarsal-carpal coalition syndrome (TCC) is caused by heterozygous mutation in the NOG gene (602991) on chromosome 17q22.
Tarsal-carpal coalition syndrome (TCC) is an autosomal dominant disorder characterized by fusion of the carpals, tarsals, and phalanges; short first metacarpals causing brachydactyly; and humeroradial fusion (Gregersen and Petersen, 1977; Drawbert et al., 1985). At birth, all affected individuals have stiffness of the proximal interphalangeal (PIP) joint of the fifth digit with or without bony synostosis. Over time, the distal end of the proximal phalanx and the proximal end of the middle phalanx fuse; progressive fusion of the PIP joints of digits 4, 3, and 2 proceeds sequentially. The distal interphalangeal joints are affected less commonly. Humeroradial fusion is not present in infancy but can be noted shortly thereafter. Abnormalities of the elbow are the most variable feature. Substantial disabilities of the ankle and foot causing painful and difficult ambulation may necessitate palliative and/or surgical intervention. Height, facial characteristics, and intelligence are normal. In contrast to proximal symphalangism (SYM1; 185800) and multiple synostoses syndrome (SYNS1; 186500), conductive hearing is typically normal in individuals with TCC (Dixon et al., 2001).
Gregersen and Petersen (1977) described a Danish kindred in which members of 4 generations showed medial synostosis of talus and calcaneus with short stature. The talus was in valgus position. An unusually large talus led to abnormalities in the development of the distal tibia and fibula. No comment was made concerning fusion of carpal bones.
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).
The transmission pattern of TCC in the families reported by Dixon et al. (2001) was consistent with autosomal dominant inheritance.
Dixon et al. (2001) mapped the TCC locus to the region between D17S790 and D17S794, which overlaps the critical interval of SYM1.
In affected members of 3 different families with TCC, including the family reported by Drawbert et al. (1985), Dixon et al. (2001) identified heterozygous mutations in the NOG gene (602991.0006-601991.0008), demonstrating that TCC is allelic to SYM1.
Dixon, M. E., Armstrong, P., Stevens, D. B., Bamshad, M. Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism. Genet. Med. 3: 349-353, 2001. [PubMed: 11545688] [Full Text: https://doi.org/10.1097/00125817-200109000-00004]
Drawbert, J. P., Stevens, D. B., Cadle, R. G., Hall, B. D., Tarsal and carpal coalition and symphalangism of the Fuhrmann type. report of a family. J. Bone Joint Surg. Am. 67: 884-889, 1985. [PubMed: 4019538]
Gregersen, H. N., Petersen, G. B. Congenital malformation of the feet with low body height: a new syndrome, caused by an autosomal dominant gene. Clin. Genet. 12: 255-262, 1977. [PubMed: 589846] [Full Text: https://doi.org/10.1111/j.1399-0004.1977.tb00938.x]
Spoendlin, H. Congenital stapes ankylosis and fusion of carpal and tarsal bones as a dominant hereditary syndrome. Arch. Otorhinolaryng. 206: 173-179, 1974. [PubMed: 4479421] [Full Text: https://doi.org/10.1007/BF00460406]
Strasburger, A. K., Hawkins, M. R., Eldridge, R., Hargrave, R. L., McKusick, V. A. Symphalangism: genetic and clinical aspects. Bull. Johns Hopkins Hosp. 117: 108-127, 1965.