Longest Living Reported Case of Congenital Myopathy with Excess of Muscle Spindles (P2.334)

Abstract

OBJECTIVE: To report the longest living case of congenital myopathy with excess of muscle spindles. BACKGROUND: The overlapping syndromes of Costello syndrome, Noonan syndrome and Cardiofacial Cutaneous syndrome have been determined to result from activating germline mutations involving the Ras-MAPK-ERK signaling cascade, aka RASopathies. A more recently discovered syndrome, CMEMS, has been linked to mutations of HRAS. To date, there are five cases of CMEMS reported in the literature; all cases were fatal by 18 months of life. Features common to this phenotype include hypertrophic cardiomyopathy, characteristic muscle pathology, hypertelorism, low-set ears, short stature, relative macrocephaly, profound weakness, hypotonia and contractures. DESIGN/METHODS: Case report RESULTS: Our patient is now 28-months-old. He presented with features of a profound congenital neuromuscular disease. He was born at 39 weeks, after a pregnancy notable for polyhydramnios and decreased fetal movement. The initial physical exam was notable for generalized arthrogryposis, hypotonia, diffuse body wall edema, talipes equinovarus, and redundant skin folds. After finding the typical pathology on muscle biopsy, CMEMS was confirmed when genetic testing was positive for the E63K mutation in the HRAS gene, specifically the c.187 G>A nucleotide substitution in exon three. Despite hypertension in the neonatal period, repeated echocardiograms have not shown evidence of cardiomyopathy. His respiratory status has fluctuated, and he currently requires ventilatory support via tracheostomy. He lives at home with his family. His intelligence appears normal, however the myopathy has prevented language development. CONCLUSIONS: Our patient lacks the cardiomyopathy seen in CMEMS, which likely contributes to his longevity. The question remains if CMEMS is sub-type of Costello syndrome or a separate nosological entity. One major barrier to comparison is that children with CMEMS have not lived past infancy. Observation of our patient may provide insight to the relationship between these two genetically similar syndromes.

Disclosure: Dr. Henry has nothing to disclose. Dr. Shiloh-Malawsky has nothing to disclose. Dr. Rowe has nothing to disclose. Dr. Fan has nothing to disclose.