The reference OMIM entry for this protein is 208100

Arthrogryposis multiplex congenita, neurogenic type; amcn
Amc, neurogenic type

CLINICAL FEATURES

Weissman et al. (1963) described an arthrogryposis-like picture consisting of flexion contractures at the elbows or knees and no dislocation of the hips. Lebenthal et al. (1970) reported further observations of the kindred studied by Weissman et al. (1963). They found 23 cases in an inbred Arab group. In a repeat study of this kindred, Jaber et al. (1995) identified 40 affected individuals. Five of the 6 individuals who were originally reported as having congenital and lethal heart defects were limited to one sibship. None of the newly identified cases had heart defect or any associated malformation. Neurologic examination and electrophysiologic studies demonstrated a neuropathic (i.e., nonmyopathic) type of arthrogryposis. Penetrance may be incomplete in females. Shohat et al. (1997) found that the most common clinical features in this family were flexion contractures of the elbows and knees and marked equinovarus. Many patients learned how to cope adequately with their handicap, and most of the adult patients were employed, some as carpenters (a common profession in this clan). Females were less affected than males; the male/female ratio was 2 to 1 and the authors concluded that there is incomplete penetrance of the disorder in females. From Israel, Krugliak et al. (1978) presented 3 autopsies of neuropathic AMC in Bedouin Arabs and commented on 2 other cases. This is presumably the same disorder as that reported by Lebenthal et al. (1970). One infant showed, in addition to depletion of spinal motor neurons, total absence of muscle spindles.

HETEROGENEITY

Burglen et al. (1996) found evidence suggesting that arthrogryposis multiplex congenita of neurogenic origin is genetically heterogeneous, with a subgroup being allelic to spinal muscular atrophy type I, or Werdnig-Hoffmann disease (SMA1; 253300). The evidence they presented came from a study of 12 patients with AMC, 6 of whom showed a deletion of SMN (600354), the survival motor neuron gene, which is implicated in SMA1. Neither point mutation in the SMN gene nor evidence for linkage to 5q13 was found in the other 6 patients. They suggested that the absence or interruption of the SMN gene would make arthrogryposis multiplex congenita-spinal muscular atrophy (AMC-SMA) easier to diagnose and would make genetic counseling feasible. Previously, one of the exclusion criteria for SMA had been arthrogryposis with severe and generalized contractures; now it is clear that some of these cases are in fact a form of SMA.

MAPPING

In a large inbred Israeli-Arab kindred with autosomal recessive AMC of the neurogenic type, Magal et al. (1997) mapped the disease locus to the terminal part of 5q. Homozygosity testing pointed to linkage with D5S1456. Formal linkage studies showed a maximum lod of 5.3 at theta = 0.001 for linkage between AMC and this marker. No recombinations were observed between D5S394 and the disease locus, which is presumably located in 5q35. Lotan et al. (1997) pointed out that the kindred studied by Magal et al. (1997) was that originally described by Weissman et al. (1963) and updated by Lebenthal et al. (1970), as mentioned earlier. Shohat et al. (1997) indicated that the AMCN locus in this family was located between markers D5S1456 and D5S498. Further fine mapping of this region allowed Tanamy et al. (2001) to narrow the critical region to a distance of 0.442 Mb between markers D5S394 and D5S2069.

ANIMAL MODEL

Arthro ... More on the omim web site

Subscribe to this protein entry history

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 208100 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).