Myopathology in patients with a Noonan phenotype

Abstract

Two patients with a Noonan phenotype and progressive hypertrophic obstructive cardiomyopathy are described, in whom abnormal histopathological changes in striated musculature were detected. In both patients an increased density of muscle spindles was found at biopsy. The significance of an increased density of muscle spindles in patients with Noonan phenotype can only be speculated. The question is raised of whether these changes are a distinct feature within the spectrum of patients with Noonan phenotype.

Congenital muscular dystrophy phenotype with neuromuscular spindles excess in a 5-year-old girl caused by HRAS mutation

“…To date, a myopathy with excess of neuromuscular spindles has been described in only five cases; four of these harbored heterozygous mutations in the HRAS gene [3]. One of the previously reported patients presented with Noonan syndrome-like facial anomalies and hypertrophic obstructive cardiomyopathy [6].…”

Myopathy caused by HRAS germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation

“…Our study population consisted of four previously reported patients [5][6][7] and one newly ascertained case. All patients presented with congenital muscular weakness.…”

Genetic heterogeneity in Noonan syndrome: Evidence for an autosomal recessive form

“…This biopsy demonstrated abnormal morphology on light microscopy with an excess of muscle spindles. These changes were interpreted as rare myopathic changes that could be added to the list of occasional findings associated with NS [de Boode et al, 1996]. The patient had feeding problems and failure to thrive.…”