SNOMEDCT: 711265009; ORPHA: 488650; DO: 0111191;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3p25.3 | Myopathy, distal, Tateyama type | 614321 | Autosomal dominant | 3 | CAV3 | 601253 |
A number sign (#) is used with this entry because the Tateyama type of distal myopathy (MPDT) is caused by heterozygous mutation in the caveolin-3 gene (CAV3; 601253) on chromosome 3p25.
Tateyama et al. (2002) reported a 25-year-old Japanese woman with muscle atrophy and weakness limited to the small muscles of the hands and feet. She first presented at age 12 years with heart palpitations, which reflected infrequent premature contractions, but heart function was normal. Serum creatine kinase was significantly elevated and she was noted to have atrophy of the hypothenar muscles. However, she had no difficulties in school or daily function. On presentation at age 25 with gastritis, she was again noted to have increased serum creatine kinase and was referred to neurology. Proximal muscle strength was normal, except for a mild weakness in neck flexion. The small muscles of the hands and feet were atrophic, and strength was decreased. EMG studies showed a myopathic pattern with decreased duration and amplitude in atrophied muscles. Muscle biopsy showed mild variation in fiber size, increased internal nuclei, and type 1 fiber predominance. There was decreased sarcolemmal immunostaining for dysferlin (DYSF; 603009) and caveolin-3. However, Western blot analysis showed normal levels of dysferlin, whereas caveolin-3 was almost absent. There was no family history of a similar disorder.
Fulizio et al. (2005) reported a mother and daughter with distal myopathy and absence of caveolin-3 protein on skeletal muscle biopsy. They presented at ages 30 and 27 years, respectively. The mother had distal weakness and calf hypotrophy, whereas the daughter had mild distal weakness only. Muscle biopsy showed moderated myopathic changes in the mother and dystrophic changes in the daughter.
Gonzalez-Perez et al. (2009) reported a Spanish family with autosomal dominant inheritance of distal myopathy and increased serum creatine kinase. The proband was a 77-year-old man who had onset in his mid-forties of distal muscle weakness and atrophy, particularly affecting the thenar and hypothenar muscles in both hands, as well as the intrinsic finger muscles. Other features included calf hypertrophy, pes cavus, and percussion-induced rapid contractions, predominantly in distal muscles of upper limbs. He had 4 affected sons, 3 of whom presented in their twenties with increased serum creatine kinase, calf hypertrophy, and pes cavus; 1 had percussion-induced rapid contractions. All later developed distal muscle weakness and atrophy affecting the hands. The fourth son, aged 33 years, had increased serum creatine kinase and pes cavus, but no evidence of motor deficit. Two granddaughters of the proband had pes cavus and increased serum creatine kinase, but no motor deficit. One had percussion-induced rapid contractions and the other had myalgias. Muscle biopsy of the proband showed slight variation in fiber size and increased number of internal nuclei, but no dystrophic changes. Caveolin-3 expression was greatly reduced in the sarcolemma, and there was a moderate reduction of dysferlin immunolabeling. Electron microscopy revealed focal loss of sarcolemma, abnormal sarcolemmal folding, absence of normal caveolae, and enlarged subsarcolemmal space with large vacuoles.
The transmission pattern of MPTD in the patient reported by Tateyama et al. (2002) was consistent with autosomal dominant inheritance.
In a Japanese woman with a relatively mild nonspecific sporadic distal myopathy, Tateyama et al. (2002) identified a heterozygous mutation in the CAV3 gene (R26Q; 601253.0007).
In a mother and daughter with distal myopathy, Fulizio et al. (2005) identified a heterozygous mutation in the CAV3 gene (N33K; 601253.0014).
In affected members of a Spanish family with distal myopathy, Gonzalez-Perez et al. (2009) identified a heterozygous R26Q mutation in the CAV3 gene. The authors emphasized the variable features in this family, such as percussion-induced rapid contractions, suggesting rippling muscle disease (RMD2; 606072).
Fulizio, L., Nascimbeni, A. C., Fanin, M., Piluso, G., Politano, L., Nigro, V., Angelini, C. Molecular and muscle pathology in a series of caveolinopathy patients. Hum. Mutat. 25: 82-89, 2005. [PubMed: 15580566] [Full Text: https://doi.org/10.1002/humu.20119]
Gonzalez-Perez, P., Gallano, P., Gonzalez-Quereda, L., Rivas-Infante, E., Teijeira, S., Navarro, C., Bautista-Lorite, J. Phenotypic variability in a Spanish family with a caveolin-3 mutation. J. Neurol. Sci. 276: 95-98, 2009. [PubMed: 18930476] [Full Text: https://doi.org/10.1016/j.jns.2008.09.009]
Tateyama, M., Aoki, M., Nishino, I., Hayashi, Y. K., Sekiguchi, S., Shiga, Y., Takahashi, T., Onodera, Y., Haginoya, K., Kobayashi, K., Iinuma, K., Nonaka, I., Arahata, K., Itoyama, Y. Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy. Neurology 58: 323-325, 2002. Note: Erratum: Neurology 58: 839 only, 2002. [PubMed: 11805270] [Full Text: https://doi.org/10.1212/wnl.58.2.323]