Lamin A/C-related dropped-head syndrome is a rapidly progressive congenital muscular dystrophy and may lead to loss of ambulation, respiratory insufficiency, and cardiac complications.
Here, we identified a novel heterozygous LMNAp.R388P de novo mutation in a patient with a non-previously described severe phenotype comprising congenital muscular dystrophy (L-CMD) and lipodystrophy.
Although lamin A/C--related congenital muscular dystrophy is a clinically distinct and recognizable phenotype, genotype/phenotype correlation, ability to anticipate onset of respiratory and cardiac involvement, and need for nutritional support remain difficult.
Thus, white matter involvement might be a feature in A-type lamin-related congenital muscular dystrophy, warranting screening of these patients for both white matter lesions and cognitive impairment.
In the last years, the spectrum of conditions has been extraordinarily enlarged, from a congenital muscular dystrophy with severe paralytic or rapidly progressive picture due to de novo mutations in LMNA (L-CMD) to a limb-girdle muscular dystrophy with adult onset and much milder weakness (LGMD1B).
Because of the survival benefit of early diagnosis and treatment, we recommend that LMNA gene sequencing be performed in all patients with undiagnosed congenital muscular dystrophy and neck extensor weakness, all patients with genetically undiagnosed LGMD, and those with suggestive clinical signs and nonspecific histologic abnormalities.
This report broadens the spectrum of lamin A/C gene mutations and illustrates the phenotypic variability of laminopathies with early onset congenital muscular dystrophy.