Dados do Trabalho

Título

VAMP1-related presynaptic congenital myasthenic syndrome

RESUMO

21-year-old male, resident in a long-stay institution for patients with cerebral palsy since the age of 5 months. Abandoned by his mother and with no information about his father or family history. There are no reports of problems during pregnancy or childbirth.
At 5 months of age, clinical evaluation showed microcephaly (-2.5 SD), global hypotonia, with decreased spontaneous movement of limbs, proximal and distal, with semiflexion of the wrists. CK was normal. The patient needed nocturnal BiPAP and exclusive G-tube feeding.Initial diagnosis was congenital myopathy. Muscle biopsy was performed at 3 years of age and showed increased variation in fiber size, type I and type II fiber atrophy, with rounded fibers and slight increase in endomysial connective tissue.
In an evaluation at 11 years of age, hypotonia and global muscle hypotrophy were observed, with proximal and distal muscle weakness (MRC grade 3 and grade 2, respectively). Deep tendon reflexes were absent. There were contractures on the knees, wrists, fourth and fifth fingers, with thoracic kyphosis, everted ankles, and flat feet. The face had a myopathic appearance with a high-arched palate. Ophthalmoparesis was predominant in vertical gaze but became global with the progression of the condition. Dysarthria was severe with barely intelligible speech. Molecular panel for neuromuscular diseases was performed at 19 years of age which demonstrated a homozygous nonsense variant in the VAMP1 gene (c.97C>T; p.Arg33*). Electromyography (EMG) demonstrated increased insertional activity, with fibrillations and positive sharp waves, as well as markedly polyphasic motor unit action potentials, with reduced recruitment and interference pattern. The above findings suggested a severe motor neuropathy, but a muscle ultrasound showed a hyperechogenic pattern, without marked muscle atrophy, suggesting that a severe neuromuscular dysfunction may be responsible for the loss of CMAP amplitude and EMG changes. Pyridostigmine was then prescribed up to a dose of 300 mg/day. Improvement after the drug treatment appeared to be slight, with a mild improvement in the movement of the upper limbs and voice turned out a little louder. VAMP1-associated presynaptic CMS is a rare form of disease from a group that is already uncommon. All cases appear to be consistent with severe congenital muscle weakness and hypotonia, with facial and bulbar involvement, and early feeding difficulties. Some patients responds to pyridostigmine.

Palavras Chave

Congenital Myasthenic Syndrome;
Neuromuscular