Dados do Trabalho

Título

MORC2 variant presenting with developmental delay, dysmorphic facies, polydactyly, and microcephaly

RESUMO

Case Presentation:
12-year-old male patient, nonconsanguineous parents, born at term, with cesarean delivery, no complications during pregnancy, childbirth or puerperium. At 9 months, neuropsychomotor development (NPDM) delay and dysmorphic facies were observed. He also presented preaxial polydactyly, which was resolved. At 12 months, he had an episode of febrile seizure. Posteriorly, it was also verified intellectual disability and hyperactivity.
During etiological investigation, brain Magnetic Resonance Imaging (MRI) revealed thin corpus callosum. Cytogenetic tests were performed, with suspicion of Fragile X Syndrome, and identified no alterations.
Besides the NPDM delay, and dysmorphic facies, the neurological examination was notable for generalized hyporeflexia, normal strength, microcephaly, and digitigrade gait. An analysis of the exome sequencing was solicited, which showed, in heterozygous, the variant hr22:30.958.684 C>T (or alternatively c.79G>A - ENST00000397641) in the MORC2 (OMIM 616661) gene, which promotes the substitution of the glutamate amino acid by lysine at the 27th codon (p.Glu27Lys). This is a rare variant, and was described in the medical literature associated with developmental delay, dysmorphic facies, and microcephaly.
Discussion:
Microrchidia CW-type zinc finger protein 2 (MORC2) encodes a DNA-dependent ATPase involved in epigenetic silencing through chromatin modification, necessary for chromatin remodeling, DNA repair, and transcriptional regulation. Heterozygous variants in the MORC2 are associated with Charcot-Marie-Tooth disease type 2Z; and developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN syndrome).
DIGFAN syndrome is an autosomal dominant neurodevelopmental disorder, associated with de novo mutations. Besides the mentioned characteristics, the patients may also present delayed acquisition of motor skills, gait abnormalities, hyporeflexia, and abnormalities on brain imaging, a phenotype similar to that of the patient described herein.
Final Comments:
Our study presents a 12-year-old male with a rare MORC2 p.Glu27Lys heterozygous pathogenic variant. We highlight the importance of MORC2 variants analysis in front of patients with global developmental delay, short stature, microcephaly, and variable dysmorphic facies.

Palavras Chave

MORC2 gene. Developmental delay. Dysmorphic facies. Microcephaly.

Área

Neurogenética