Dados do Trabalho

Título

Distal presentation in central core myopathy caused by RYR1 mutations: a CMT-like phenotype.

RESUMO

Case report
A 16-year-old patient, with no consanguinity in the family, presented with frequent falls and tip-toe gait, at the age 2. She developed a distal leg weakness with significant deformities. On examination, she presented global hyporeflexia, MRC grade 4 in the proximal upper and lower limbs. She had a more intense distal lower limbs weakness (MRC 3), with deformities in pes cavus, hammer fingers and aquileus retractions.
Due to the marked presentation of distal weakness with the described deformities, she was initially diagnosed with Charcot-Marie-Tooth (CMT) disease and referred to our center. On investigation, we found normal levels of creatine phosphokinase (CK); no evidence of polyneuropathy was seen in neurophysiological studies. Biopsy of brachial biceps muscle revealed well delimited cores by the staining of NADH-TR. MRI showed involvement of paravertebral and posterior compartment of the leg muscles. The whole exome sequencing showed two missense likely pathogenic variants in RYR1 (p.Phe41Ser and p.Gly4686Asp).
Discussion
The RYR1 gene encodes the rianodine 1 receptor channel and is the main cause of susceptibility to malignant hyperthermia and a wide spectrum of congenital myopathies, including central core myopathy (CCM). CCM is characterized by central cores on muscle biopsy and clinical features of a congenital myopathy with autosomal dominant (AD) and recessive (AR) inheritance patterns. The patients present predominantly proximal weakness pronounced in the hip girdle with orthopedic complications. On the other hand, classic CMT phenotype reflects length-dependent axonal degeneration represented by distal sensory loss and weakness, deep tendon reflex abnormalities, and skeletal deformities.
According to an international cohort of 21 AR RYR1-related CCM patients, all of them had predominantly proximal muscle weakness. Although most had some involvement of distal muscle groups, distal weakness was as severe as proximal weakness in only 4. An early exclusively distal phenotype has not been reported in the main studies of CCM.
Final comments
Our patient presented an atypical phenotype for RYR1-related CCM, with predominantly distal weakness and feet deformities that resembled the CMT phenotype. RYR1 must be considered as a cause of distal myopathies. Pes cavus and hammer fingers are not specific for CMT.

Palavras Chave

RYR1, Central Core Miopathy, CMT phenotype