Related Experiment Video
Updated: Mar 3, 2026
Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
Clinical Features in Children with Persistent Toe Walking Who Carry Heterozygous PYGM Variants: A Cross-Sectional
David Pomarino1, Bastian Fregien2, Kevin M Rostásy3
1Pomarino. Praxis für Ganganomalien, Hamburg, Germany.
Insights
Heterozygous PYGM variants may be linked to subtle neuromuscular issues in children with persistent toe walking (TW). Genetic testing may aid in identifying underlying conditions when TW is suspected.
Area of Science:
- Neuromuscular Disorders
- Pediatric Neurology
- Clinical Genetics
Background:
- Persistent toe walking (TW) in children can indicate underlying neuromuscular or metabolic conditions.
- Investigating genetic factors like PYGM variants is crucial for understanding idiopathic TW.
- Heterozygous carriers of PYGM variants may present with subclinical phenotypes.
Purpose of the Study:
- To investigate the clinical and genetic characteristics of children with persistent toe walking carrying PYGM variants.
- To explore potential subclinical neuromuscular phenotypes in heterozygous PYGM variant carriers.
Main Methods:
- Cross-sectional, retrospective study of 72 children with idiopathic TW.
- Utilized a standardized clinical protocol and a 49-gene next-generation sequencing neuromuscular panel.
- Classified variants according to ACMG/AMP guidelines.
Main Results:
- 72 PYGM variant carriers identified among 1,300 screened patients.
- All carriers exhibited bilateral toe walking; 80.5% had severe dorsiflexion restriction.
- Pes cavus (93%), muscle symptoms (approx. 1/3), and speech difficulties (56.9%) were common.
- 12.5% could perform heel walking; VUS carriers showed milder muscle symptoms than P/LP carriers.
Conclusions:
- Heterozygous PYGM variants may contribute to subtle neuromuscular phenotypes in children with persistent toe walking.
- Genetic testing for PYGM variants can be considered in persistent TW cases with suspected underlying neuromuscular/metabolic conditions.
Objectives:
Persistent toe walking (TW) in children is often idiopathic but may conceal subtle neuromuscular or metabolic causes. This cross-sectional, retrospective study investigated clinical and genetic characteristics of children carrying PYGM variants to explore potential subclinical phenotypes among heterozygous carriers.
Methods:
Seventy-two (72) children meeting criteria for idiopathic TW were evaluated using a standardized clinical protocol and a validated 49-gene next-generation sequencing neuromuscular panel. Variants were classified as pathogenic, likely pathogenic, or of uncertain significance according to ACMG/AMP guidelines. Analyses were descriptive.
Results:
Among 1,300 screened patients, 72 were identified as PYGM variant carriers. Toe walking was bilateral in all cases, with severe dorsiflexion restriction (≤ 5°) in 80.5%. Pes cavus was observed in 93% of patients, and muscle symptoms-pain, fatigue, or cramps-occurred in approximately one-third. VUS carriers displayed comparable, slightly milder muscle symptom frequencies than P/LP carriers. 12.5% could perform heel walking. Speech difficulties were reported in 56.9% of cases.
Conclusions:
While causality cannot be inferred, these findings suggest that heterozygous PYGM variants may contribute to subtle neuromuscular phenotypes. Genetic testing can be considered in persistent TW when clinical findings raise suspicion for an underlying neuromuscular/metabolic condition.
Related Concept Videos
01:35Pedigree Analysis
01:43Incomplete Dominance
01:33Pleiotropy
01:11Genetic Lingo
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:18Polygenic Traits