IQSEC2-related developmental and epileptic encephalopathy with a Rett-like phenotype: two cases with novel variants and a review of the literature - Report - MDSpire
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IQSEC2-related developmental and epileptic encephalopathy with a Rett-like phenotype: two cases with novel variants and a review of the literature
Clinical Report: Developmental and Epileptic Encephalopathy Associated with IQSEC2 Variants
Overview
This report describes two brothers with a novel IQSEC2 truncating variant presenting with Rett-like syndrome features, including developmental delay and refractory epilepsy. A review of 38 additional cases highlights male predominance and variable regression patterns, emphasizing the need for routine IQSEC2 screening in similar patients.
Background
IQSEC2 variants are increasingly recognized as a cause of developmental and epileptic encephalopathy, particularly in males, and can present with symptoms resembling Rett syndrome. Understanding the genotype-phenotype correlations is crucial for accurate diagnosis and management. The clinical overlap with MECP2-related Rett syndrome complicates the diagnostic process, necessitating genetic testing for definitive identification.
Data Highlights
No numerical data available in the article.
Key Findings
Two brothers with a novel IQSEC2 truncating variant exhibited developmental delay, microcephaly, and refractory epilepsy.
Male predominance was noted among the 40 cases reviewed, contrasting with the female predominance in classic Rett syndrome.
Regression of skills occurred inconsistently, suggesting a potential developmental arrest rather than true regression.
Missense mutations clustered in functionally critical domains, while truncating mutations were more dispersed.
Patients with larger duplications or deletions exhibited greater phenotypic variability.
Clinical Implications
Routine genetic screening for IQSEC2 variants should be considered in patients presenting with unexplained developmental and epileptic encephalopathy, particularly those with Rett-like features. Clinicians should be aware of the distinct clinical presentation and variability associated with IQSEC2 mutations to guide management and counseling.
Conclusion
The findings underscore the importance of recognizing IQSEC2 variants in the context of developmental and epileptic encephalopathy, facilitating timely diagnosis and intervention.
