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A novel INPP4A mutation with pontocerebellar hypoplasia, myoclonic epilepsy, microcephaly, and severe developmental

Pınar Özkan Kart1, Senol Citli2, Nihal Yildiz1

  • 1Faculty of Medicine, Department of Pediatric Neurology, Farabi Hospital, Karadeniz Technical University, Trabzon, Türkiye.

Brain & Development
|February 9, 2023
PubMed

Insights

Mutations in the INPP4A gene can cause severe neurological disorders, including pontocerebellar hypoplasia and epilepsy. Early identification of INPP4A variants is crucial for diagnosing these rare genetic conditions.

Area of Science:

  • Genetics
  • Neuroscience
  • Molecular Biology

Background:

  • The inositol polyphosphate 4-phosphatase (INPP4A) intracellular signaling pathway plays a critical role in cellular function.
  • Alterations in this pathway are implicated in various neurological disorders, particularly those affecting the pons and cerebellum.

Observation:

  • A seven-year-old girl presented with a severe neurological phenotype including pontocerebellar hypoplasia, resistant myoclonic epilepsy, microcephaly, and developmental delay.
  • Whole-exome sequencing identified a homozygous pathogenic variant (c.646C>T, p.(Arg216Ter)) in the INPP4A gene.

Findings:

  • The identified homozygous INPP4A variant likely disrupts the inositol polyphosphate 4-phosphatase activity.
  • This genetic defect is associated with the patient's complex neurological presentation, including pontocerebellar abnormalities and intractable epilepsy.

Implications:

  • INPP4A mutations should be considered in the differential diagnosis of severe psychomotor delay, progressive microcephaly, and epilepsy with cerebellar and pontine involvement.
  • Understanding the role of INPP4A in neurological development can inform future diagnostic and therapeutic strategies for related disorders.
Abstract

Keywords:
Myoclonic seizuresNovel INPP4A mutationPontocerebellar hypoplasiaWES

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