2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Case Report: NFIA-related Disorder Caused by Inherited Missense Mutations Leading to Variable Presentations Among Family Members

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This document provides information about three family members who have been diagnosed with NFIA-related disorder, a genetic condition characterized by hypoplasia of the corpus callosum, macrocephaly, and developmental delay. The patients include a 6-year-old male (Patient 1), a 10-year-old female (Patient 3), and a 31-year-old female (Patient 2, the mother).<br /><br />Patient 1 had a history of seizures, developmental delay, and joint hypermobility. Additional findings included enlarged kidneys and unusual physical features. Genetic testing revealed a likely pathogenic variation in the NFIA gene, confirming the diagnosis of NFIA-related disorder.<br /><br />Patient 3 had seizure-like activity, developmental delay, and autism spectrum disorder. Musculoskeletal abnormalities and unusual physical features were also present. Genetic testing showed that the patient shared the familial NFIA variant with the mother and brother.<br /><br />The mother (Patient 2) had a history of psychiatric disorders, renal calculi, and musculoskeletal issues. Genetic testing initially identified a variant in the TNX-B gene, but further testing revealed that the mother also shared the familial NFIA variant with her children.<br /><br />The document highlights the difficulty in identifying NFIA-related disorder and the importance of obtaining the correct diagnosis for appropriate care and prognosis. The study also discusses the potential relationship between different types of NFIA gene mutations and specific clinical features, such as ventriculomegaly and Chiari I malformation.<br /><br />Additionally, the document explores the involvement of NFIA in muscle development and regeneration, suggesting that defective NFIA function may contribute to the muscle hypotonia observed in patients with NFIA-related disorder.<br /><br />Overall, this study provides valuable insights into the clinical manifestations and genetic features of NFIA-related disorder, contributing to a better understanding of this rare genetic condition.

Asset Subtitle

Presenting Author - Peyton Paschell, MS; Co-Author - Jacquelyn Johnson, MS, CGC; Co-Author - Christina Laukaitis, MD, PhD;

Meta Tag

Musculoskeletal system

Intellectual disability

Inheritance Patterns

Genotype-Phenotype Correlations

Exome sequencing

Brain/Nervous System

Bone/Joint Abnormalities

Co-Author Christina Laukaitis, MD, PhD

Co-Author Jacquelyn Johnson, MS, CGC

Presenting Author Peyton Paschell, MS

Keywords

NFIA-related disorder

hypoplasia of the corpus callosum

macrocephaly

developmental delay

seizures

joint hypermobility

enlarged kidneys

autism spectrum disorder

musculoskeletal abnormalities

genetic testing