A novel FLNA missense variant in a mother–daughter pair with epilepsy: case series evidence of variable multisystem expressivity

Beyond Rett syndrome: a case series expanding the neurological spectrum associated with pathogenic MECP2 variants

Clinical and Genetic Findings in a Turkish Family With the Recurrent Homozygous EEFSEC p.Asp390Ala Variant.

The EEFSEC gene encodes eukaryotic elongation factor selenocysteine-tRNA-specific, an essential component of the selenoprotein biosynthesis machinery required for normal neurodevelopment. Biallelic EEFSEC variants have recently been associated with a rare autosomal recessive neurodevelopmental disorder with variable neurological severity. Here, we describe a Turkish proband carrying the recurrent homozygous EEFSEC (NM_021937.5) variant c.1169A>C; p.Asp390Ala, together with his younger brother, who was identified with the same homozygous variant through familial testing. The proband presented with intellectual disability, delayed motor and expressive language development, mild hypotonia, subtle dysmorphic features, and self-limited early childhood febrile seizures. Compared with previously reported Turkish patients carrying the same variant, his absence of ocular motor involvement, normal neuroimaging, lack of persistent epileptiform abnormalities, and partial developmental gains suggest a relatively milder neurological presentation. The younger brother was initially identified before overt neurological manifestations and subsequently showed delayed expressive language development during early follow-up. This report provides comparative data on the recurrent EEFSEC p.Asp390Ala variant and highlights the value of familial testing, early molecular diagnosis, and longitudinal developmental monitoring in families with confirmed biallelic EEFSEC variants.

Novel Compound Heterozygous Variants in SLC13A3 Associated With ARLIAK: A Case Report and Review of the Literature

SLC13A3 pathogenic variants are associated with acute reversible leukoencephalopathy and α‐ketoglutarate accumulation (ARLIAK), a rare neurological disorder characterized by recurrent episodes of encephalopathy and transient white matter abnormalities. Pathogenic variants reported so far include missense, nonsense and small deletion variants, highlighting substantial allelic heterogeneity. We describe a patient presenting with multiple episodes of acute encephalopathy, elevated urinary α‐ketoglutarate and reversible white matter lesions on MRI, consistent with SLC13A3‐related ARLIAK. Genetic analysis identified novel compound heterozygous variants: a missense variant (p.Leu46Pro) in a highly conserved region and a larger deletion encompassing exons 2–3. Our findings indicate that conventional sequencing alone may miss larger deletions, suggesting the need for copy number analysis as part of the diagnostic protocol for suspected ARLIAK cases. The elevated urinary α‐ketoglutarate in our patient supports its potential as a noninvasive biomarker. MRI findings demonstrated typical transient and reversible white matter abnormalities, aligning with previously reported cases. This study expands the molecular and phenotypic spectrum of SLC13A3‐related ARLIAK and underscores the importance of combining sequencing with copy number analysis for accurate diagnosis. The identification of novel variants contributes to a better understanding of the disease mechanism and suggests a broader allelic heterogeneity than previously recognized.

A novel mutation in SETD1A is associated with early-onset epilepsy—a rare case report

This study may expand the mutation and phenotypic spectrum of SETD1A-related disorders, establishing the relationship between SETD1A variants and isolated early-onset epilepsy without accompanying severe neurodevelopmental deficits, and highlighting the value of genetic testing in infants with unexplained epilepsy.

A Novel de Novo WAC Frameshift Variant in DeSanto-Shinawi Syndrome With Temporo-Occipital Epileptiform Activity and Congenital Cardiac Anomalies.

DeSanto-Shinawi syndrome (DESSH) is a rare autosomal dominant neurodevelopmental disorder associated with heterozygous pathogenic variants in the WAC gene, most commonly resulting in loss of function. The clinical spectrum of DESSH continues to expand, whereas detailed electroencephalographic descriptions remain limited. We report a 9-year-old male patient presenting with developmental delay, behavioral abnormalities, dysmorphic facial features, epilepsy, and congenital cardiac anomalies. Brain magnetic resonance imaging was normal, while serial electroencephalography demonstrated persistent epileptiform activity involving the bilateral temporo-occipital regions, with left temporo-occipital persistence on follow-up. Whole-exome sequencing identified a novel heterozygous apparently de novo frameshift variant in WAC (NM_016628.5:c.1793delT; p.Met598Serfs*8), which was classified as pathogenic according to ACMG/AMP criteria. The variant is predicted to result in loss of function, supporting haploinsufficiency as the most plausible disease mechanism. This case expands the mutational and clinical spectrum of DESSH and provides additional electroclinical data on epilepsy associated with WAC-related neurodevelopmental disorder. The coexistence of ventricular septal defect and bicuspid aortic valve further supports the multisystemic nature of the syndrome. Our findings highlight the importance of detailed neurological, electroencephalographic, cardiac, and genetic evaluation in patients with suspected DESSH.

A case report of a novel de novo variant in PPP2CA causing a neurodevelopmental disorder and epilepsy

The findings support the pathogenicity of this variant and further expand the pathogenic variant spectrum of the PPP2CA gene, and the observed genotype–phenotype correlation provides valuable information for prognosis and genetic counseling.