P87-F Severe congenital myopathy related to a novel mutation in the titin gene. A case report

Abstract

Mutations in the titin gene (TTN) are related to a wide spectrum of disease. In recent years, congenital titinopathy has emerged as a cause of severe early onset myopathy. A case of two female sisters born at 32 weeks of gestation by cesarean section, from a non-consanguineous, healthy couple. They had normal prenatal ultrasounds except from equinovarus foot in one twin. Apgar score was low at birth (6–10 at 1 and 5 min in both). Both girls needed ventilator support because of respiratory insufficiency, severe axial hypotonia, multiple joint contractures distal and proximal and multiple long bone fractures. Chromosomopathy and osteogenesis imperfect were ruled out in the Genetic unit of our institution. Cardiological studies were normal. The neurographic study performed at two months of life showed extremely low amplitudes of the CMAPs with normal conduction velocities and relative preservation of the SNAPs, without clear myopathic features or spontaneous activity in the needle EMG. The whole exome sequencing (GenExComplete) revealed two extremely rare mutations in the titin gene, only expressed in the fetal skeletal transcript of TTN. One of the twins died at 8 months of age from pneumonia and the other baby needs mechanical ventilation for life support to date. In a case of severe congenital myopathy without cardiac involvement, it is essential to consider the global clinical context. Although very rare, mutations in the fetal skeletal transcript of TTN should be excluded.