EP.60There is not loss of ambulation in three DMD brothers after 16 years old

Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations leading to absent dystrophin. DMD phenotype encompasses muscle weakness and wasting presenting in early childhood with loss of independent ambulation by 13 years, while in the mild allelic form Becker muscular dystrophy (BMD) is after 16 years. Interestingly, nonsense mutation DMD shows a loss of ambulation at 11.1 years, with a few outliers carrying stop codons mutations within in-frame exons are still ambulatory around or after 16 years of age. With daily glucocorticoid treatment and improved standards of care the loss of ambulation in DMD is around 14 years, with a wide variability attributed to different treatment regimens, and genetic modifiers. We describe a family with 3 brothers with history of delayed psychomotor development manifesting by 3 years of age with progressive proximal weakness, characteristic gait, positive Gowers sign, and calf pseudohypertrophy. They had very high serum CK levels and liver enzymes. Diagnostic genetic testing performed by multiplex PCR and MLPA were negative. Two of the 3 patients underwent muscle biopsies and showed traces of dystrophin of carboxyl terminal and rod region identified by inmunohistochemical analysis. Afterwards, sequencing of DMD gene was performed finding a hemizygous variant: c.10141C>T p. (Arg3381*). ClinVar lists this variant as pathogenic. In all of them an intellectual disability was found. They have received treatment with levocarnitive supplements in the beginning for one year, and deflazacort after. They still have ability to perform the 10 m run/walk assessment and go up and down 3 stairs. This mutation has been reported in dystrophinopathies and dilated cardiomyopathy, in these patients the phenotype corresponds to DMD/BMD; and the variants in the terminal carboxyl region in the dystrophin gene are associated with mental retardation; which corresponds to the phenotype observed in patients.