Background: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from dysfunction of the protein myotubularin encoded by the
MTM1 gene. XLMTM has a high neonatal and infantile mortality rate due to a severe myopathic phenotype and respiratory failure. However, in a
[...] Read more.
Background: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from dysfunction of the protein myotubularin encoded by the
MTM1 gene. XLMTM has a high neonatal and infantile mortality rate due to a severe myopathic phenotype and respiratory failure. However, in a minority of XLMTM cases, patients present with milder phenotypes and achieve ambulation and adulthood. Notable facial dysmorphia is also present. Methods: We investigated the genotype–phenotype correlations in newly diagnosed XLMTM patients in a patients’ cohort (previously published data plus three novel variants,
n = 414). Based on the facial gestalt difference between XLMTM patients and unaffected controls, we investigated the use of the Face2Gene application. Results: Significant associations between severe phenotype and truncating variants (
p < 0.001), frameshift variants (
p < 0.001), nonsense variants (
p = 0.006), and in/del variants (
p = 0.036) were present. Missense variants were significantly associated with the mild and moderate phenotype (
p < 0.001). The Face2Gene application showed a significant difference between XLMTM patients and unaffected controls (
p = 0.001). Conclusions: Using genotype–phenotype correlations could predict the disease course in most XLMTM patients, but still with limitations. The Face2Gene application seems to be a practical, non-invasive diagnostic approach in XLMTM using the correct algorithm.
Full article
