A de novoNR2F1 c.330 C > A variant in Bosch-Boonstra-Schaaf optic atrophy syndrome presenting with early-onset developmental and epileptic encephalopathy

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.

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

RFX3 Pathogenic Variants as a Rare Cause of Infantile Epileptic Spasms Syndrome

This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption, and highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders.

Biallelic SLC20A2 loss-of-function in severe early-onset neurodevelopmental disorder with brain calcification.

Findings support a dose-dependent SLC20A2 disease spectrum and expand the phenotype associated with biallelic loss of function from primary brain calcification toward severe early-onset neurodevelopmental disorder with prominent vascular and leptomeningeal calcification.

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.

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.