Peer-reviewed article
Expanding the clinical and molecular spectrum of SETD5, NEDD4L, and TBL1X related disorders: A case report and literature review.
Marco Cassone, Antonino Moschella, Davide Mei, Asia Costa, Antonella Garro ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a medical case report describing a single child with genetic variants affecting neurodevelopment, seizures, and hormone regulation. The report documents three rare genetic mutations identified through exome sequencing and discusses their potential contribution to the child's clinical presentation. While the case involves a child, it is a clinical genetics study focused on identifying disease mechanisms rather than evaluating child well-being or interventions to improve outcomes.
Key points
- A male child presented with intellectual disability, seizures, and periventricular nodular heterotopia
- Exome sequencing identified three rare genetic variants in SETD5, NEDD4L, and TBL1X genes
- The SETD5 variant is consistent with neurodevelopmental delay; TBL1X with central hypothyroidism
- NEDD4L variant is a candidate for the periventricular nodular heterotopia phenotype
- First reported case of this specific combination of three genetic variants
Limitations
This is a single case report describing genetic findings in one child; it provides no information about interventions, treatment outcomes, or the broader well-being of children with these conditions. The study cannot establish the prevalence, prognosis, or effectiveness of any treatments for affected children.
Abstract
We report a unique clinical case of a male child presenting with a blended phenotype characterized by intellectual disability, seizures, periventricular nodular heterotopia (PVNH), congenital central hypothyroidism, and multiorgan malformations. Exome sequencing (ES) identified three rare variants: a de novo frameshift variant in SETD5 (g.3-9441593 ;NM_001080517.3:c.812dup; p.(Leu271PhefsTer42)), a de novo missense variant in the WW domain of NEDD4L (NM_015277.6:c.1525C > T; p.(Arg529Cys)), and a maternally inherited nonsense variant in TBL1X (X-9711651-C-T) (NM_005647.4:c.1480C > T; p.(Arg494Ter)). While the likely pathogenic SETD5 and TBL1X variants are consistent with the neurodevelopmental delay and central hypothyroidism respectively, the NEDD4L variant of uncertain significance (VUS) represents a plausible candidate for the PVNH. To our knowledge, this is the first report of such a unique overlap, highlighting the importance of considering multilocus genomic variation in heterogeneous neurodevelopmental presentations.