#156250
ICD+
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| METACHONDROMATOSIS | |||||||||||||||||||||||||||
| Phenotype Gene Relationships | |||||||||||||||||||||||||||
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| Clinical Synopsis | |||||||||||||||||||||||||||
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| A number sign (#) is used with this entry because metachondromatosis is caused by mutation in the PTPN11 gene (176876) on chromosome 12q24. | |||||||||||||||||||||||||||
| Clinical Features | |||||||||||||||||||||||||||
| Maroteaux (1971) described 2 families with skeletal radiologic features of both multiple exostoses (133700) and Ollier disease (166000). He called the disorder metachondromatosis and suggested autosomal dominant inheritance on the basis of 1 family with 5 affected persons. Lachman et al. (1974) reported a case. Kennedy (1983) presented the case of a 9.5-year-old boy in whom 'bumps' on the hands, feet and knees had been noted at age 5. In the next few years, some of these enlarged, new ones appeared, and others regressed. Peculiar striations were noted radiologically in the metaphyses of the long bones and iliac crests. The mother had a similar although milder history; x-ray showed a single exostosis in the wrist. The maternal grandfather had had lesions of the hands, feet, and knees, but none was evident at the time of radiologic study. Two cousins were said to have similar lesions. Differentiation from multiple exostoses of the classic type (133700) is important because of the usual regression with little or minimal residual deformity. Involvement of the hands and feet is the rule in metachondromatosis but is said by Kennedy (1983) to be unusual in classic multiple exostoses. Furthermore, in metachondromatosis, the exostoses point toward the epiphysis. Dorst (1983) observed metachondromatosis in a brother and sister of Korean extraction. The radiologic findings combined those of multiple exostoses, multiple enchondromatosis (Ollier disease), and dysplasia epiphysealis hemimelica (127800). No other affected relatives were known but the parents were not available for study. In the family studied by Vanek (1982), the mother of 2 of the affected persons had a history of exostoses as a child, which regressed as she grew older. X-ray studies showed no peripheral exostoses but the proximal end of one humerus was wide and a first metatarsal was abnormally thin. A brother was said also to have had nodular growths near joints as a child. Bassett and Cowell (1985) studied 4 members of a kindred that had at least 8 cases in all. They pointed out that the enchondromatous lesions involve the iliac crest and metaphyseal region of the long bones of the lower extremities as in Ollier disease. The exostoses of metachondromatosis, unlike those of hereditary multiple exostosis, point toward the nearby joint and do not cause shortening or bowing of the long bone, joint deformity, or subluxation. They affect particularly the digits and may resolve spontaneously. | |||||||||||||||||||||||||||
| Mapping | |||||||||||||||||||||||||||
| Sobreira et al. (2010) performed a genomewide scan in a 5-generation family segregating autosomal dominant metachondromatosis and identified 6 regions showing suggestive evidence for linkage, including chromosome 7p14.1 (maximum lod score, 2.5), 8q24.1, and 12q23 (lod score of 1.8 for both), and 2p25, 5q12.1, and 9q31.1-q33.1 (lod scores between 1.0 and 1.5). | |||||||||||||||||||||||||||
| Molecular Genetics | |||||||||||||||||||||||||||
| Sobreira et al. (2010) performed whole-genome sequencing in 1 affected individual from a 5-generation family with metachondromatosis and identified a heterozygous 11-bp deletion in the PTPN11 gene (176876.0025); analysis of family members confirmed that the deletion segregated with the disease. Sequencing of the PTPN11 gene in another 3-generation family with autosomal dominant metachondromatosis revealed a heterozygous nonsense mutation (176876.0026) in affected individuals. Neither mutation was detected in 469 controls. | |||||||||||||||||||||||||||
| See Also: | |||||||||||||||||||||||||||
| De la Cruz and Garcia-Castro (1976); Giedion et al. (1975) | |||||||||||||||||||||||||||
| REFERENCES | |||||||||||||||||||||||||||
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