On the basis of two paediatric cases of myopathies linked to the RYR1 gene and a review of the literature, a Japanese team has highlighted the complexity of genetic counselling in these diseases, linked to their possible dual mode of inheritance, via an autosomal dominant or recessive mode.
- It is difficult to distinguish between these two modes of transmission on the basis of clinical data alone, even though patients with autosomal recessive inheritance present more severe phenotypes.
- Two sporadic cases are described in this publication. The first patient has a de novo missense mutation with autosomal dominant inheritance, while the second has two heterozygous missense mutations, each inherited from one parent with autosomal recessive inheritance.
- The parents were informed of the risk of inheritance in the event of a future pregnancy via genetic counselling (low for the first and not negligible for the second).
- A review of the literature highlights the importance of a complete genomic analysis of all RYR1 coding regions in the patient and his or her parents to improve genetic counselling, particularly in the absence of a family history.
- Prenatal diagnosis may be useful for future pregnancies in cases of autosomal recessive inheritance.
Genetic counselling would be facilitated by the creation of a database enabling each mutation in the RYR1 gene to be correctly assessed, taking into account the mode of inheritance with which they are associated.
