In a previous study published in 2024, Marie Morimoto et al. described nine cases of a new congenital myopathy linked to biallelic variants of the RFC4 gene, the Morimoto-Ruy-Malicdan syndrome. This syndrome is characterised by coordination problems, muscular and respiratory weakness, hearing impairment, weight loss and cerebellar atrophy. A new study of two brothers of Ukrainian origin, aged three and eight, supplements these data.
- Both brothers had previously undescribed biallelic variants in the RFC4 gene, corresponding to protein modifications p.[Gly341Lysfs*4] and [Thr328delinsAsnSer].
- The authors were able to establish a causal link between the gene and the phenotype observed.
- In the older brother, the first symptoms appeared as early as the neonatal period, while in the younger brother they appeared at six months. Among the cases already described, the time of onset of the first signs ranged from the neonatal period to adulthood.
- The disease progressed rapidly in both brothers after the age of one, with severe muscle weakness affecting mainly the axial and cervical muscles, hearing loss, short stature, cerebellar atrophy and particularly severe hypotonia.
- Both brothers acquired the ability to walk independently, although the older brother lost this ability at the age of seven.
- Psychological evaluation revealed normal intellectual development in both brothers.
- Four of the nine cases described above died between the ages of 7 months and 49 years. However, the two brothers had no respiratory or cardiac complications and did not require feeding tubes.
The description of these two new cases clarifies the phenotypic spectrum of this syndrome. Diagnostic approaches such as whole-exome sequencing and whole-genome sequencing, combined with data-sharing platforms, could make it possible to identify new cases.
