Case report: Novel compound heterozygosity for pathogenic variants in MED23 in a syndromic patient with postnatal
Emanuela Salzano1, Marcello Niceta2, Simone Pizzi2
1Medical Genetics Unit, AOOR Villa Sofia-Cervello Hospitals, Palermo, Italy.
Abstract:
Biallelic loss-of-function variants in MED23 cause a recessive syndromic intellectual disability condition with or without epilepsy (MRT18). Due to the small number of reported individuals, the clinical phenotype of the disorder has not been fully delineated yet, and the spectrum and frequency of neurologic features have not been fully characterized. Here, we report a 5-year-old girl with compound heterozygous for two additional MED23 variants. Besides global developmental delay, axial hypotonia and peripheral increased muscular tone, absent speech, and generalized tonic seizures, which fit well MRT18, the occurrence of postnatal progressive microcephaly has been here documented. A retrospective assessment of the previously reported clinical data for these subjects confirms the occurrence of postnatal progressive microcephaly as a previously unappreciated feature of the phenotype of MED23-related disorder.
Insights
Biallelic loss-of-function variants in MED23 cause a rare neurodevelopmental disorder. This study identifies postnatal progressive microcephaly as a previously unrecognized feature of this condition.
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- MED23 variants are associated with a rare recessive syndromic intellectual disability (MRT18).
- The full clinical and neurological spectrum of MED23-related disorder remains incompletely characterized due to limited reported cases.
Observation:
- A 5-year-old girl presented with compound heterozygous MED23 variants.
- Clinical features included global developmental delay, hypotonia, absent speech, and seizures, consistent with MRT18.
Findings:
- The patient exhibited postnatal progressive microcephaly, a feature not previously well-documented in MED23-related disorder.
- Retrospective analysis of existing literature supports postnatal progressive microcephaly as an underappreciated aspect of the MED23 phenotype.
Implications:
- This finding expands the known phenotypic spectrum of MED23-related intellectual disability.
- Enhanced understanding of MED23 disorder may improve diagnostic accuracy and clinical management for affected individuals.
