P.295 - C-terminal binding protein 1 (CtBP1) deficiency, mimicking congenital myopathy during infancy

Abstract

The CtBP1 gene was identified as transcriptional co-repressor that modulates gene expression in multiple cellular pathways. CtBP1 plays a critical role during human embryogenic period. CtBP1 gene presents an active role in myogenesis and post synaptic membrane receptor formation. Its has been associated recently with human disease. Hypotony and muscle weakness are two of the most relevant clinical features, however its effects in muscle pathology has not been described enough . Herein, we describe the fifth reported patient, who showed a similar phenotype of former described patients, sharing the same mutation. Currently is 8 year- old girl born from a non-consanguineous parent. Because her early hypotonia, motor development delay and myogenic EMGs patterns, congenital myopathy was suspected. Muscle biopsy performed at 3 years old showed, atrophic and hypertrophic fibers with abnormal intermyofibrillar network in several fibers. Electron microscope revealed disruption of sarcomeres with Z-line streaming, Intermyofibrillar neatwork disruption and absence of mitochondria. These features extended from 1 to 4–5 sarcomeres. At that time, truncal ataxia was noticed evolving to a progressive cerebellar syndrome, losing their motor and cognitive acquired abilities and developing a severe scoliosis. Tooth enamel defects were also observed. Exome sequencing studies confirmed a heterozygous p.R331W mutation in CtBP1 gene, previously reported and affecting all the former described patients. Segregation analysis did not show this variant in neither of the parents in her brother. Mutation in CtBP1 may be considered as a congenital regressive and severe condition affecting several organs. Because hypotonia is one of the main and first clinical symptoms, CTBP1 deficiency must be added to causes of floppy infant syndrome.