PPP2R5D-Related Neurodevelopmental Disorder or Developmental and Epileptic Encephalopathy?: A Novel Phenotypic Description and Review of Published Cases

Abstract

Background Protein phosphatase 2 regulatory subunit B′ delta (PPP2R5D)-related neurodevelopmental disorder is caused by pathogenic variations in the PPP2R5D gene, product of which is involved in dephosphorylation. This is a rare disorder with description limited to case reports. Its phenotypic spectrum has expanded over the last decade.

Methods We report a child with a developmental and epileptic encephalopathy phenotype with a pathogenic PPP2R5D variant. This phenotype has not been previously reported. We also reviewed the previously published reports of patients with this disorder.

Results Including the index child, 28 cases (15 girls) were identified from nine relevant research items for analysis. All patients had developmental delay. History of seizures was observed in seven patients while macrocephaly was seen in nearly 80% of patients. Nonneurological manifestations were observed in 13 patients with the most common one being ophthalmological manifestations. The most common genetic variation was c.G592A (p.E198K). The common phenotypic associations of this variation were developmental delay, macrocephaly (11/15), and epilepsy (6/15).

Conclusion PPP2R5D gene variations should be suspected in children with developmental delay, autistic features, macrocephaly with or without epilepsy in the absence of any clear etiology. Dysmorphic features might provide a diagnostic clue. DEE phenotype may also be the presenting feature and might be an underreported entity.

Keywords

PPP2R5D - epilepsy - DEE - neurodevelopmental disorder

Authors' Contribution

P.M. and A.K. contributed by patient management, literature search, qualitative synthesis, and writing of the manuscript.

S.V. contributed by interpretation of neuroradiological images and critical review of manuscript.

A.R.S. contributed by literature search, qualitative synthesis, and critical review of manuscript.

P.P., and J.K.S. contributed by patient management and critical review of the manuscript.

L.S. contributed by patient management, writing, and critical review of manuscript.

All authors approved the final version of manuscript to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declarations of Interest

None.

^* Contributed equally and share first authorship.

Publication History

Received: 02 November 2020

Accepted: 04 January 2021

Article published online:
26 August 2021

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