A new variant in MYH2 gene in an Italian patient expands the clinical spectrum of Congenital Myopathy-6 with ophthalmoplegia (CMYP6)

Elenco Abstract

Monica Sciacco

A new variant in MYH2 gene in an Italian patient expands the clinical spectrum of Congenital Myopathy-6 with ophthalmoplegia (CMYP6)

Autori

SIMONA ZANOTTI (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY, – BIOLOGA)
DARIO RONCHI (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY; DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, DINO FERRARI CENTER, UNIVERSITY OF MILAN, MILAN, ITALY – BIOTECNOLOGO)
LAURA NAPOLI (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY, – BIOLOGA)
MICHELA RIPOLONE (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY, – BIOLOGA)
PATRIZIA CISCATO (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY, – TECNICO DI LABORATORIO)
ROBERTO DEL BO (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY – BIOLOGO)
FRANCESCA MAGRI (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY – MEDICO NEUROLOGO)
GIACOMO PIETRO COMI (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY; DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, DINO FERRARI CENTER, UNIVERSITY OF MILAN, MILAN, ITALY – MEDICO NEUROLOGO)
STEFANIA CORTI (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY; DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, DINO FERRARI CENTER, UNIVERSITY OF MILAN, MILAN, ITALY – MEDICO NEUROLOGO)
MONICA SCIACCO (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY, – MEDICO NEUROLOGO)

Presentatore

MONICA SCIACCO (IRCCS FONDAZIONE CÀ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY)

Modalità

Poster Session

Abstract

Myosin heavy chain (MYHC)-related congenital myopathies display variable age of onset and clinical manifestations depending on the mutated isoform. Cardiomyopathy, ophthalmoplegia and primarily proximal weakness may be part of the clinical picture
A 57-year-old male patient with a history of arterial hypertension and hyperferritinemia (thalassemic trait) began to experience lower limb proximal weakness at the age of 23 years and he got progressively worse over the years when he also reported mild dyspnea, easy fatigability, fasciculations and a sort of discomfort in the posterior muscles of both thighs even at rest. He had no diplopia or dysphagia. Serum CK values were slightly elevated (less than 300 U/L). His parents are second-degree cousins and have normal serum CK levels, a proband’s first cousin had a diagnosis of muscular dystrophy and died at the age of 60 years, wheelchair-bound. A 46-year-old sister is healthy.
EMG showed signs of reinnervation in all muscles, myopathic signs being evident in the gastrocnemius muscles. Fibroadipose degeneration was seen at muscle MRI. Peculiar clinical features were bilateral exophthalmos, slight eyelid ptosis, limited ocular motility in all gaze directions, marked lower limb proximal weakness with posteromedial thigh hypotrophy and hypertrophic calves with increased consistency.
Severe signs of both myopathic and neurogenic degeneration were seen at quadriceps skeletal muscle biopsy. Genetic analysis revealed a new homozygous mutation (c.3901G>T) in MYH2 gene (NM_017534) causing a premature stop p.(Glu1301*) in exon 29 thus leading to a diagnosis of congenital myopathy-6 with ophthalmoplegia (CMYP6). The phenotype-gene spectrum of this pathology is discussed.