Alternative titles; symbols
SNOMEDCT: 1179297007; DO: 0110288;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q14.3 | ?Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue | 616827 | Autosomal recessive | 3 | LIMS2 | 607908 |
A number sign (#) is used with this entry because of evidence that autosomal recessive muscular dystrophy with cardiomyopathy and triangular tongue (MDRCMTT) is caused by compound heterozygous mutation in the LIMS2 gene (607908) on chromosome 2q14. One such family has been reported.
Autosomal recessive muscular dystrophy with cardiomyopathy and triangular tongue (MDRCMTT) is an autosomal recessive muscle disorder characterized by onset of severe and progressive muscle weakness and atrophy in childhood, resulting in loss of independent ambulation. Patients may also have dilated cardiomyopathy and have macroglossia with a small tip, resulting in a triangular appearance of the tongue (summary by Warman Chardon et al., 2015).
Warman Chardon et al. (2015) reported 2 adult sibs, born of unrelated parents of northern European ancestry, with onset of progressive proximal muscle weakness at about 5 years of age. Both had normal earlier motor development. Features included calf hypertrophy and weakness of the lower and upper limbs progressing to severe quadriparesis; both were wheelchair-bound by age 12. The weakness started proximally but eventually also involved the distal muscles of the upper and lower limbs. At age 35 years, the brother was diagnosed with symptomatic dilated cardiomyopathy with hypokinesis; the sister had asymptomatic moderate dilated cardiomyopathy. Cardiac MRI suggested fibrotic changes. Both patients also had macroglossia that was less evident at the tip, giving the tongue a triangular appearance. Serum creatine kinase was increased; muscle biopsy showed dystrophic features with variation in fiber size, scattered necrotic fibers, and increased connective tissue. Muscle imaging of the sister showed severe muscle atrophy and fat infiltration, consistent with muscular dystrophy. Cognition was unaffected.
The transmission pattern of MRDCMTT in the family reported by Warman Chardon et al. (2015) was consistent with autosomal recessive inheritance.
In 2 sibs, born of unrelated parents, with MDRCMTT, Warman Chardon et al. (2015) identified compound heterozygous mutations in the LIMS2 gene (607908.0001 and 607908.0002). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants were not performed, but skeletal muscle biopsy of 1 patient showed a marked reduction in LIMS2 protein immunostaining at the Z-disc compared to controls.
Warman Chardon, J., Smith, A. C., Woulfe, J., Pena, E., Rakhra, K., Dennie, C., Beaulieu, C., Huang, L., Schwartzentruber, J., Hawkins, C., Harms, M. B., Dojeiji, S., Zhang, M., FORGE Canada Consortium, Majewski, J., Bulman, D. E., Boycott, K. M., Dyment, D. A. LIMS2 mutations are associated with a novel muscular dystrophy, severe cardiomyopathy and triangular tongues. Clin. Genet. 88: 558-564, 2015. [PubMed: 25589244] [Full Text: https://doi.org/10.1111/cge.12561]