Vici syndrome associated with sensorineural hearing loss and evidence of neuromuscular involvement on muscle biopsy

Abstract

Vici syndrome is a rare, genetically unresolved congenital multisystem disorder comprising agenesis of the corpus callosum, cataracts, immunodeficiency, cardiomyopathy, and hypopigmentation. An associated neuromuscular phenotype has not previously been described in detail. We report on an infant with clinical features suggestive of Vici syndrome and additional sensorineural hearing loss. Muscle biopsy revealed several changes including markedly increased variability in fiber size, increased internal nuclei, and abnormalities on Gomori trichrome and oxidative stains, raising a wide differential diagnosis including neurogenic atrophy, centronuclear myopathy (CNM) or a metabolic (mitochondrial) cytopathy. Respiratory chain enzyme studies, however, were normal and sequencing of common CNM-associated genes did not reveal any mutations. This case expands the clinical spectrum of Vici syndrome and indicates that muscle biopsy ought to be considered in infants presenting with suggestive clinical features. In addition, we suggest that Vici syndrome is considered in the differential diagnosis of infants presenting with congenital callosal agenesis and that additional investigation has to address the possibility of associated ocular, auditory, cardiac, and immunologic involvement when this radiologic finding is present.

Emerging role of autophagy in pediatric neurodegenerative and neurometabolic diseases

“…29 Further neurological manifestations include microcephaly, nonlissencephalic cortical dysplasia, cerebellar vermis hypoplasia, severe cognitive and motor impairment, seizures, muscular hypotonia, and failure to thrive. [29][30][31] The disease is usually fatal in early childhood. Reports of available muscle biopsies record myopathic features with type 1 atrophy and glycogen accumulation.…”

Clinical utility gene card for: Vici Syndrome

“…In general, genetic confirmation of the diagnosis will result in a more careful assessment for known (for example, CNS malformations, cataracts, cardiomyopathy and combined immunodeficiency) but also often overlooked associations (for example, sensorineural deafness, 6 thyroid, liver and kidney involvement 1 ) that may be amenable to therapeutic interventions. More specifically, recognizing the presence of neuromigrational abnormalities and the associated increased epilepsy risk will result in more timely institution of anticonvulsant therapy where indicated.…”

“…1,[3][4][5][6][7][8][9][10][11][12] However, a proportion of cases are probably either undiagnosed or unreported, suggesting that this figure provides an underestimate of the actual frequency. Vici syndrome has been found in equal frequencies in the different ethnic groups studied.…”

“…Where performed, supportive features on muscle biopsy include light microscopy abnormalities comprising increased fiber size variability, increased internal nuclei and vacuolization, 6 and ultrastructural changes on electron microscopy such as numerous vacuoles 3 and abnormalities of mitochondrial morphology and localization.…”

Congenital myopathies

“…Most patients had a genetic diagnosis, with core myopathies and RYR1 mutations, respectively, the most common histopathologic and genetic diagnoses, as reported. 11,13,25 Bearing in mind that the defining features of the CMs (such as FTD, nemaline rods, cores, and central nuclei) are not specific and may occur in other clinical situations, 26 including CNS developmental malformations 27 and recently recognized multisystem disorders with primary autophagy defects, 28,29 we took great care that only patients with clinicopathologic features of a CM without evidence of other underlying conditions were included in this study. The onset of clinical signs was observed predominantly within the first year of life: approximately half of the patients presented in the neonatal period with severe feeding and respiratory complications, as described.…”