# Homozygous Pathogenic MYH3 Variants Associated With Arthrogryposis and Lingual Dystonia

## TL;DR

This paper reports a family with a genetic mutation in MYH3 causing skeletal and movement disorders, including a rare tongue condition.

## Contribution

The study identifies MYH3 homozygous variants as causative for both skeletal and neurological symptoms, expanding the known phenotype.

## Key findings

- Two homozygous MYH3 variants (c.3445G>A and c.4760T>C) were found in four siblings with arthrogryposis and lingual dystonia.
- No other significant genetic variations were detected using long-read whole genome sequencing.
- The findings suggest that MYH3 mutations may cause underdiagnosed movement disorders in addition to skeletal abnormalities.

## Abstract

Heterozygous pathogenic variants in MYH3 are known to be responsible for distal arthrogryposis.

We report a consanguineous family of four children with two likely pathogenic MYH3 homozygous variants associated with complex movement disorders, especially prominent lingual dystonia, along with skeletal abnormalities. The two variants in MYH3 (c.3445G>A and c.4760T>C) have already been described in patients with congenital arthrogryposis. No other significant variation was found using long-read whole genome sequencing.

We have extended the phenotype of MYH3-associated arthrogryposis to include movement disorders, which may have been underdiagnosed to date.

This article extends the phenotype of MYH3-associated arthrogryposis to include movement disorders, illustrating a family of four children presenting MYH3 skeletal disorders and lingual dystonia. Two homozygous likely pathogenic variants have been identified in the four sibs and appear to be causative for both skeletal and neurological phenotypes.