Case report: DIGFAN syndrome

*Correspondence: [e-mail].

Abstract

Case Presentation: A 6-year-old male patient with regression of motor development from 1 year of age, microcephaly, peripheral neuropathy, seizures and severe malnutrition at the time of evaluation. Pre and perinatal and past pathological history without intercurrences. Brain MRI showed significant diffuse volumetric reduction of the cerebellum and minimal dysgenetic changes in the corpus callosum and electroneuromyography with chronic findings of lower motor neuron dysfunction. Panel for lysosomal and neuromuscular diseases without alterations. Exome sequencing was performed, which showed heterozygous de novo pathogenic alterations in the MORC2 gene.

Discussion: The DIGFAN syndrome (Developmental delay, impaired growth, dysmorphic facies and axonal neuropathy) is characterized by delay or regression of neuropsychomotor development, hypotonia, growth deficit, usually associated with short stature, microcephaly, subtly dysmorphic facial features and neuroimaging changes such as cerebral or cerebellar atrophy, hypomyelination, and lesions in the basal ganglia or brainstem may also occur. Some pathogenic de novo variants in the MORC2 gene are associated with the phenotypic expression of this condition.

Final Comments: In addition to DIGFAN syndrome, pathogenic alterations in MORC2 are associated with a wide phenotypic variability that encompasses diseases such as Marie-Charcot-Tooth and Spinal muscular atrophy in adults, making the identification of this syndrome a diagnostic challenge. Despite being a rare condition, the analysis of this gene should be considered in genetic panels, such as neurodevelopmental disorders and neuromuscular diseases, for its recognition and early intervention.

Publication History

Article published online:
12 May 2025