Despite having a chronic illness and prolonged ventilator dependence, many
patients with MTM1 have linear growth above the 50th percentile; some
patients in the US series achieved greater than 90th percentile for height.
An advanced bone age and/or premature adrenarche have been documented in
several boys, suggesting some disturbance of endocrine regulation; however,
results of endocrinologic studies performed in several patients have been
normal. Puberty has occurred normally in the few patients who have reached
adulthood, although reproduction by an affected male has not been
documented. Cognitive development in the majority of patients is normal if
no significant hypoxic episodes have occurred. The muscle disease is not
progressive, and muscle strength improves slowly over time. Medical
complications related to the underlying myopathy are ophthalmoplegia,
ptosis, severe myopia, dental malocclusion (requiring orthodontic care), and
scoliosis. Scoliosis often develops in later childhood and may require
surgical intervention. Scoliosis can exacerbate respiratory insufficiency
and can cause some ventilator-independent boys to become ventilator
dependent again as the condition progresses. With more aggressive supportive
care and longer survival of some patients with MTM1, medical complications
unrelated to the muscle disorder have occurred; these complications include
pyloric stenosis, a mild form of spherocytosis, gallstones, kidney stones,
nephrocalcinosis, a vitamin K-responsive bleeding diathesis, and liver
dysfunction manifested by pruritus and elevated serum transaminases. Several
patients have died following prolonged liver hemorrhage or hemorrhage into
the peritoneal cavity. In three patients, peliosis hepatis, a rare vascular
lesion characterized by the presence of multiple blood-filled cysts within
the liver, was noted. Authors are aware of several additional unreported
cases of boys with MTM1 and liver dysfunction, peliosis, or hemorrhage into
the peritoneum. The pathogenetic mechanisms for these complications are not
understood, but their lack of occurrence in other congenital myopathies and
neuromuscular disorders, such as spinal muscular atrophy, strongly suggests
that they are related to abnormal function of or absence of myotubularin.