A classical phenotype of Duchenne muscular dystrophy in a girl with X; autosome translocation.

Dear Sir,

Dystrophinopathies are diseases that affect skeletal muscles and are caused by mutations of the dystrophin gene at locus Xp21, with Duchenne muscular dystrophy (DMD) being the most common. DMD is X-linked, occurring in 1 in every 3500 boys.[1] The absence of the protein dystrophin leads to progressive muscle necrosis, loss of walking in early puberty, cardiac muscle involvement, respiratory failure and death at an early age.[1] Varying degrees of clinical symptoms are seen in 10% of carrier females; in X chromosome monosomies like Turner syndrome or X; autosome translocation involving the dystrophin gene, females may exhibit the severe clinical form typically seen in males.[2] In order to draw attention to the classical phenotype of DMD occurring in females, we present a 2.5-year-old girl with DMD.

A 2.5-year-old female patient was referred to us with elevated creatine kinase (CK) levels. Patient and family history were unremarkable. The patient walked unassisted, spoke in one-word utterances, but did not form two-word sentences. Gowers's sign and pseudohypertrophy of both calves were observed. Serum CK level was 14,026 IU/L. The muscle biopsy revealed dystrophinopathy. Deletion/duplication analysis for dystrophinopathies performed using multiplex ligation-dependent probe amplification (MLPA) showed no mutation. Karyotype analysis revealed a balanced translocation that included locus Xp21 [46, X, t (X,13;17)(p21;q13;q22)]. Karyotype analysis of the mother showed 46, XX, demonstrating de novo translocation for the child. Array-based comparative genomic hybridization performed to assess the possibility of deletion/duplication in translocation breakpoints or any other loci unrelated to breakpoints showed no changes. Patient features were attributed to the breakpoint being in the dystrophin gene. The family was informed of the classical DMD prognosis for the patient due to the translocation. Physical therapy was started. Echocardiogram was normal.

Duchenne muscular dystrophy generally follows a severe course in boys, while girls rarely show symptoms. One of the few exceptions for this is X; autosome translocation involving dystrophin gene locus. During female fetal life, random X-inactivation occurs. In cases with X; autosome translocation, classical DMD phenotype in girls is seen because normal X chromosome is mostly inactivated. Normal X chromosome is sacrificed as the inactivation of a translocated X chromosome leads to the inactivation of the autosomal loci on it.[34]

In conclusion, DMD may lead to severe clinical symptoms in girls resembling males. When no mutation is detected in girls by Becker muscular dystrophy/DMD deletion/duplication analysis using MLPA, karyotype analysis can help pinpoint the choromosomal abnormality responsible for the overt disease state. Identifying the type of the chromosomal abnormality may help determine the prognosis for the patient.