“We report on a 3-years-old patient born from consanguineous parents presenting with clinical history of global developmental delay, hypotonia, lower limb girdle weakness and high level of creatine phosphokinase (8.000 IU/l).
The neurological examination revealed in addition the presence of macrocrania, intellectual disability and ataxic signs. Brain MRI displayed mild cerebellar atrophy and ventricular enlargement, visual evoked potentials showed alterations of central conduction, and a sensory motor demyelinating neuropathy was detected. Considering the association of myopathic signs and central nervous system (CNS) involvement, a congenital muscular dystrophy was suspected.
Muscle biopsy disclosed dystrophic abnormalities and reduced expression of alpha-dystroglycan and dystrophin. Next Generation Sequencing panel revealed a homozygous variant in the SGCG gene (c.525delT; p.F175Lfs*19), inherited from both parents, leading to an unexpected diagnosis of sarcoglycanopathy. Subsequently the younger brother showed a similar clinical presentation and carried the same SGCG variant. According to the literature, SGCG mutations are associated with limb girdle muscular dystrophy (LGMDR5) and a concomitant CNS involvement has never been reported.
Further diagnostic investigations were thus performed at the aim to identify a second genetic disease: CGH array, FMR-1 and PTEN gene analysis resulted negative. Whole exome study on all family members DNA is currently in progress.
This case report provides evidence that rare pathologies can coexist and overlap; we suggest that in presence of unusual clinical features and multisystem impairment the diagnostic workflow should always be widen. The diagnosis of two diseases has a relevant impact on patients medical care, management and familiar counseling.”