Alternative titles; symbols
SNOMEDCT: 205082007; ORPHA: 178382, 295201, 295203; DO: 0111568;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q31.1 | Charcot-Marie-Tooth disease, foot deformity of | 192950 | Autosomal dominant | 3 | HOXD10 | 142984 |
| 2q31.1 | Vertical talus, congenital | 192950 | Autosomal dominant | 3 | HOXD10 | 142984 |
A number sign (#) is used with this entry because of evidence that isolated congenital vertical talus (CVT) is caused by heterozygous mutation in the HOXD10 gene (142984) on chromosome 2q31.
Congenital vertical talus (CVT), also known as 'rocker-bottom foot' deformity, is a dislocation of the talonavicular joint characterized by vertical orientation of the talus with a rigid dorsal dislocation of the navicular, equinus deformity of the calcaneus, abduction deformity of the forefoot, and contracture of the soft tissues of the hind- and mid-foot. This condition is usually associated with multiple other congenital deformities and only rarely is an isolated deformity with familial occurrence (summary by Levinsohn et al., 2004). The condition is transmitted in an autosomal dominant pattern of inheritance, and sometimes shows incomplete penetrance and variable expressivity. There may be a broad spectrum of deformities, including flatfoot, talipes equinovarus (TEV or clubfoot), cavus foot, metatarsus adductus, and even hypoplasia of the tibia (summary by Dobbs et al., 2006).
Levinsohn et al. (2004) provided detailed clinical features of an Italian family with CVT reported by Shrimpton et al. (2004). There were 11 individuals with isolated bilateral CVT apparent at infancy spanning 4 generations in an autosomal dominant pattern. Radiographic studies showed vertical orientation of the talus with dorsal dislocation of the navicular. Four additional family members, 2 with CVT and 2 without CVT, developed cavovarus foot deformities similar to those seen in Charcot-Marie-Tooth disease (see CMT1A, 118220) in their teenage years. However, nerve conduction and electromyographic testing were not performed on the 4 CMT-affected individuals to confirm that diagnosis in this family. Patients younger than 30 years were unable to run fast; patients between 30 and 60 years reported discomfort with prolonged standing; and patients older than 60 years had severe degenerative arthritis of the feet. Affected family members demonstrated only foot abnormalities; hands, vertebrae, and mental faculties were all normal. Levinsohn et al. (2004) noted the unusual finding of cavo-varus in this family and suggested that different times of action of the mutated gene led to different phenotypic appearances.
Dobbs et al. (2006) reported a large English family (family F) in which 6 individuals spanning 3 generations had isolated bilateral congenital vertical talus. None had signs or symptoms of CMT, and nerve conduction velocity studies in 1 patient were normal.
Lamy and Weissman (1939) noted familial occurrence of 'congenital convex pes valgus.' These authors described CVT in a mother and child and cited instances of affected identical twins and father/son involvement.
Ogata et al. (1979) found that 16 of 36 patients with congenital vertical talus had a primary isolated form; the other patients had other associated deficits. Fifty percent of the patients with the isolated form reported an affected first-degree relative, suggesting a genetic component.
Hamanishi (1984) described an affected woman and son. Stern et al. (1987, 1989) demonstrated vertical transmission of congenital vertical talus through 3 generations of a Honduran family. There was incomplete penetrance in a woman with 2 affected children. Nine members of the family were affected in all. Bilateral and unilateral involvement was seen with a wide range of severity. There was no evidence of associated malformations or neuromuscular disease.
Dobbs et al. (2002) reported 4 unrelated families with autosomal dominant transmission of CVT. Detailed examination of family members, including several cases with unaffected parents, suggested variable expression and incomplete penetrance.
The transmission pattern of CVT in the family reported by Dobbs et al. (2006) was consistent with autosomal dominant inheritance and full penetrance.
In a family with congenital vertical talus and other foot deformities, Shrimpton et al. (2004) performed whole-genome linkage analysis and defined a 7-Mb critical region on chromosome 2q31.
In 14 members of a family of Italian extraction with isolated CVT, Shrimpton et al. (2004) identified a heterozygous missense mutation in the HOXD10 gene (M319K; 142984.0001). Two of the patients with isolated CVT developed pes cavus later in life. Two additional family members with isolated pes cavus also carried the mutation. The mutation was found by linkage analysis followed by candidate gene sequencing.
In affected members of an English family with isolated bilateral congenital CVT, Dobbs et al. (2006) identified the M319K mutation. Sequencing of the HOXD10 gene in 5 additional families and 5 patients with sporadic CVT did not identify any mutations, indicating genetic heterogeneity of the condition. Functional studies of the variant were not performed.
Dobbs, M. B., Gurnett, C. A., Pierce, B., Exner, G. U., Robarge, J., Morcuende, J. A., Cole, W. G., Templeton, P. A., Foster, B., Bowcock, A. M. HOXD10 M319K mutation in a family with isolated congenital vertical talus. J. Orthop. Res. 24: 448-453, 2006. [PubMed: 16450407] [Full Text: https://doi.org/10.1002/jor.20052]
Dobbs, M. B., Schoenecker, P. L., Gordon, J. E. Autosomal dominant transmission of isolated congenital vertical talus. Iowa Orthop. J. 22: 25-27, 2002. [PubMed: 12180606]
Hamanishi, C. Congenital vertical talus: classification with 69 cases and new measurement system. J. Pediat. Orthop. 4: 318-326, 1984. [PubMed: 6736236]
Lamy, L., Weissman, L. Congenital convex pes valgus. J. Bone Joint Surg. 21: 79-91, 1939.
Levinsohn, E. M., Shrimpton, A. E., Cady, R. B., Packard, D. S., Hootnick, D. R. Congenital vertical talus in four generations of the same family. Skeletal Radiol. 33: 649-654, 2004. [PubMed: 15368082] [Full Text: https://doi.org/10.1007/s00256-004-0851-1]
Ogata, K., Schoenecker, P. L., Sheridan, J. Congenital vertical talus and its familial occurrence: an analysis of 36 patients. Clin. Orthop. Relat. Res. 139: 128-132, 1979. [PubMed: 455829]
Shrimpton, A. E., Levinsohn, E. M., Yozawitz, J. M., Packard, D. S., Jr., Cady, R. B., Middleton, F. A., Persico, A. M., Hootnick, D. R. A HOX gene mutation in a family with isolated congenital vertical talus and Charcot-Marie-Tooth disease. Am. J. Hum. Genet. 75: 92-96, 2004. [PubMed: 15146389] [Full Text: https://doi.org/10.1086/422015]
Stern, H. J., Clark, R. D., Shohat, M., Stroberg, A. J. Autosomal dominant transmission of isolated congenital vertical talus. (Abstract) Am. J. Hum. Genet. 41: A86 only, 1987.
Stern, H. J., Clark, R. D., Stroberg, A. J., Shohat, M. Autosomal dominant transmission of isolated congenital vertical talus. Clin. Genet. 36: 427-430, 1989. [PubMed: 2591068]