Rare CCND2 (p.Thr280Ile) Variant Associated With Infantile Spasms in a Patient With Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology Pub Date : 2024-09-21 DOI:10.1016/j.pediatrneurol.2024.09.016

Kent M. Mok MD , Jessica L. Carpenter MD , Pamela Herrada MS, CGC , Carol Greene MD , Sandrine Yazbek MD , Gozde Erdemir MD

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引用次数: 0

Abstract

Background

This report describes a pediatric case of megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, a rare neurodevelopmental disorder caused by pathogenic variants in the AKT3, CCND2, or PIK3R2 genes. We present a patient with a rare CCND2 variant (c.839C>T, p.Thr280Ile), associated with infantile spasms, ventriculomegaly, polymicrogyria, and intraventricular hemorrhage (IVH).

Methods

A retrospective chart review and literature search were performed using PubMed.

Results

Our patient was found to have ventriculomegaly, grade 3 IVH, bilateral polymicrogyria, and restricted diffusion in the caudate nuclei prenatally. No polydactyly was observed. The patient developed infantile spasms at age 5 months. While high-dose prednisone treatment failed to control the spasms, they resolved with topiramate. By age 2 years, the patient continued to have significant developmental delays, including having poor tone and being nonverbal.

Conclusion

MPPH syndrome remains a rare and challenging diagnosis, with fewer than 100 cases reported. This case highlights the importance of early genetic testing and neuroimaging in the diagnosis and management of MPPH. The unique presentation of IVH and restricted diffusion warrants further investigation into the syndrome’s variable phenotypic spectrum. Early intervention and targeted therapy may help manage seizure activity and improve outcomes.

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罕见的 CCND2（p.Thr280Ile）变异与巨脑畸形-多发性畸形-多指畸形-脑积水综合征患者的婴儿痉挛有关

背景本报告描述了一例巨脑-多小脑-多乳-脑积水（MPPH）综合征的儿科病例，这是一种由 AKT3、CCND2 或 PIK3R2 基因致病变体引起的罕见神经发育障碍。我们报告了一名患有罕见CCND2变异（c.839C>T, p.Thr280Ile）的患者，该患者伴有婴儿痉挛、脑室肥大、多发性畸形和脑室内出血（IVH）。结果我们发现患者有脑室肥大、3级IVH、双侧多发性畸形和出生前尾状核弥散受限。未发现多指畸形。患者在 5 个月大时出现婴儿痉挛症。虽然大剂量强的松治疗未能控制痉挛，但使用托吡酯后痉挛得到缓解。到 2 岁时，患者仍有明显的发育迟缓，包括音调不佳和不善言语。本病例强调了早期基因检测和神经影像学检查在 MPPH 诊断和治疗中的重要性。IVH和弥散受限的独特表现值得进一步研究该综合征的多变表型谱。早期干预和针对性治疗有助于控制癫痫发作活动和改善预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric neurology 医学-临床神经学

CiteScore

4.80

自引率

2.60%

发文量

176

审稿时长

78 days

期刊介绍： Pediatric Neurology publishes timely peer-reviewed clinical and research articles covering all aspects of the developing nervous system. Pediatric Neurology features up-to-the-minute publication of the latest advances in the diagnosis, management, and treatment of pediatric neurologic disorders. The journal''s editor, E. Steve Roach, in conjunction with the team of Associate Editors, heads an internationally recognized editorial board, ensuring the most authoritative and extensive coverage of the field. Among the topics covered are: epilepsy, mitochondrial diseases, congenital malformations, chromosomopathies, peripheral neuropathies, perinatal and childhood stroke, cerebral palsy, as well as other diseases affecting the developing nervous system.