Dados do Trabalho

Título

LMOD3-related nemaline myopathy (NEM10): new insights based in two brazilian cases.

RESUMO

Case 1: Male, 5 months old, polyhydramnios and reduced fetal movement, born with generalized hypotonia, cyanosis, respiratory distress, and irregular breathing. Submitted to orotracheal intubation, tracheostomy and gastrostomy. Inspection: elongated and hypotonic face, bilateral palpebral ptosis, adducted thumb and fifth finger, flaccid and areflex tetraparesis. Received pyridostigmine (20mg/kg), evolving with increased mobility in the shoulder girdle, trunk, and extremities of the upper limbs. No side effects were observed. Case 2: male, 19 years old, son of consanguineous parents, hypotonia since birth, delay in motor milestones, mild dysarthria, elongated and hypotonic face, bilateral palpebral ptosis, generalized amyotrophy and muscle weakness with distal predominance, adducted thumb, and steppage gait. Muscle Biopsy showed nemaline bodies. EMG in both cases revealed a myopathic pattern. Repetitive stimulation identified a decrement of 18.8% in case 2. Received pyridostigmine with a subjective improvement. Molecular analysis identified in both cases 2 different variants (homozygosis) in LMOD3 gene. Discussion: Nemaline myopathy (NM) is a congenital myopathy defined by the presence of rod-like structures, called nemaline bodies, in myofibers, caused by 13 genes. The LMOD3 is associated with a severe birth-onset form of NM (NEM10). We describe the first two Brazilian cases of NEM10. Out of 34 cases reported in the literature, 5 reached adulthood. Our Case 1 has a severe form with a non-sense variant (c.154del), previously described in a Portuguese family. Case 2 has a mild form, with a missense variant (c.1194G>C) not previously described. There seems to be a genotype-phenotype correlation in NEM10, based on the type of consequence of the variant and the position of the amino acid in the protein, determining a more severe (case 1) or milder (case 2) phenotype. The presence of decrement is a classic finding of neuromuscular junction disease (NMJD), however, it has also been described in subtypes of congenital myopathy. So, these patients may have a good response to acetylcholinesterase inhibitors. Final Comments: Our cases are the first NEM10 cases in the literature with a partial response to pyridostigmine. The use of pyridostigmine in NM was reported in one case related to KLHL40, with significant improvement. Therefore, we should consider using pyridostigmine in NM as an alternative therapy.

Palavras Chave

nemaline myopathy; congenital myopathy; LMOD3; NEM10; pyridostigmine;