Abstract Details

Title Cylindrical Spirals Congenital Myopathy Associated with Epileptic Encephalopathy

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) P07 - (-)

Poster/Presentation
Number 050

Objective

Background BACKGROUND: Cylindrical spirals (CSs) congenital myopathy is characterized by the presence of peculiar lamellar structures consisting of concentric membranous whorls found at electron microscopy analysis of muscle biopsies. These structures are composed of a spiraling double-laminated membrane, which, in transverse muscle sections, resemble to "onion bulb". Since their first description, CSs have been reported in few cases, with the majority of patients presenting isolated muscle involvement.

Design/Methods DESIGN/METHODS: We report on the clinical data, histochemical and ultrastructural features of skeletal muscle biopsy of a consanguineous family of Antillean (mother) and Moroccan (father) origin.

Results RESULTS: The proband presented neonatal onset hypotonia accompanied by refractory tonic-clonic and myoclonic epilepsy. Cardiac examination was normal. Ancillary investigations showed elevated serum lactates. Molecular screening of mitochondrial DNA (mtDNA) MELAS and MERRF mutations was normal. A muscle biopsy, performed at 1 year and 1 month of age, revealed the presence of intermyofibrillar and subsarcolemmal "rimmed" vacuoles filled of fuchsinophilic material reacting at Gomori Trichrome staining. These structures are present in only type II fibres and strongly stain with NADH-TR or Menadione alpha-glycerophosphate reactions. Ultrastructural analysis demonstrated the presence of subsarcolemmal and intermyofibrillar spheroidal/ovoidal structures containing concentric lamellae resembling spirals. These structures are intermingled by glycogen or tubular structures. The elder sister of the proposita presented a milder phenotype characterised by muscle hypotonia and epileptic encephalopathy when she was 7 months old. The mother suffers of epileptic crisis.

Conclusions CONCLUSIONS: We describe the first pedigree presenting congenital myopathy with cylindrical spirals associated with central nervous system involvement. Through a fine morphological and ultrasturctural study we speculate about the mechanism leading to the formation of CSs. Our study prelude to exome sequencing analysis aimed at identifying the molecular defect underlying this condition.

Authors/Disclosures
Edoardo Malfatti, MD (APHP, Inserm U955, Université Paris Est) PRESENTER	Dr. Malfatti has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Spark therapeutics. Dr. Malfatti has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. The institution of Dr. Malfatti has received research support from AFM. The institution of Dr. Malfatti has received research support from Spark Therapeutics. The institution of Dr. Malfatti has received research support from AFM. The institution of Dr. Malfatti has received research support from ANR.
Marcelo Chaves (Merck Serono Argentina)	No disclosure on file
	No disclosure on file
Thomas A. Berger, MD (Dept. of Neurology, Medical University of Vienna)	Prof. Berger has received personal compensation in the range of $10,000-$49,999 for serving as a speaker at scientific meetings and participant of local and international advisory boards with various companies producing and markerting treatments for multiple sclerosis (Almirall, Biogen, Biologix, Bionorica, Celgene-BMS, Merck, Novartis, Roche, Sanofi-Genzyme, TG Therapeutics, UCB).
	No disclosure on file
Michel Fardeau, MD	No disclosure on file
	No disclosure on file

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