Developmental disorder and facial dysmorphia syndrome caused by a mutation in the MORC2 gene

Pathogenic nucleotide variants in the MORC2 gene have recently been linked to axonal peripheral neuropathy (Charcot–Marie–Tooth disease, axonal type 2Z) and the syndrome of developmental and growth disorders, facial dysmorphia, and axonal neuropathy (DIGFAN syndrome). DIGFAN syndrome is marked by early onset and multisystem symptoms, particularly affecting the visual and auditory organs. In approximately 30% of cases, mitochondrial encephalomyopathy is initially considered a possible diagnosis. In a girl with a heterozygous MORC2 gene mutation, the presence of DIGFAN syndrome was confirmed. Her clinical profile included motor, speech, and physical developmental delays, along with visual and auditory impairments, peripheral neuropathy, facial dysmorphia, Lee-like changes on MRI, and moderate lactic acidemia. Following metabolic therapy targeting intracellular energy exchange processes, alongside a rehabilitation program, some improvement in her condition and normalization of blood lactate levels were observed. The importance of early diagnosis is highlighted, as it supports the timely initiation of metabolic therapy and other therapeutic interventions under specialist supervision. Confirming the diagnosis is critical for anticipating disease progression and providing genetic counseling for the proband and their family.

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