Journal of Pediatric Neurology
DOI: 10.1055/s-0041-1725017
Case Report

A Case of Prenatally Diagnosed Periventricular Nodular Heterotopia in a Surviving Male Patient with FLNA Mutation

1  Division of Neurology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
,
Akash Virupakshaiah
1  Division of Neurology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
,
Ian M Campbell
2  Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
,
Elaine H. Zackai
2  Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
,
Deborah Zarnow
3  Division of Radiology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
,
Sonika Agarwal
1  Division of Neurology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
› Institutsangaben
Funding None.

Abstract

FLNA is a gene on the X chromosome that encodes Filamin A, a widely expressed protein crucial for forming the cell cytoskeleton and mediating cell signaling. Loss-of-function mutations have been associated with periventricular nodular heterotopia (PVNH) with associated epilepsy and intellectual deficits, as well as cardiovascular disease, connective tissue disorders, pulmonary disease, bleeding diathesis, and gastrointestinal disease. Alternatively, gain-of-function mutations have been described with otopalatodigital spectrum disorders.

The loss-of-function variants of FLNA associated with PVNH have historically been considered lethal in males, often prenatally or by the first year of life. However, more surviving males with FLNA variants are being described. Most of the surviving males have missense or distal truncating mutations or a degree of mosaicism. Others are thought to have splice site mutations or in-frame exon skipping leading to production of some degree of functional Filamin A as possible mechanisms of survival.

Here, we present a case of a 20-month-old small but developmentally appropriate and healthy male infant who was prenatally diagnosed with PVNH, and postnatally found to have a nonsense variant of the FLNA gene. This mutation has not been previously clinically described or published to our knowledge.

Authors' Contributions

J.T. was involved in drafting and revision of manuscript for intellectual content and collection of data.


A.V. was involved in drafting and revision of manuscript for intellectual content and collection of data.


I.C. was involved in revision of manuscript for intellectual content and collection of data. D.Z. was involved in collection of data and manuscript preparation. E.H.Z. was involved in revision of manuscript for intellectual content. S.A. was involved in revision of manuscript for intellectual content.




Publikationsverlauf

Eingereicht: 06. Januar 2021

Angenommen: 19. Januar 2021

Publikationsdatum:
19. Februar 2021 (online)

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