Toe Walking as the Initial Symptom of a Spinocerebellar Ataxia 13 in a Patient Presenting with a Mutation in the KCNC3 Gene

This article at hand described a 4-year-old patient who initially presented with the symptoms of toe walking. As part of the diagnostic process, the patient was genetically tested to find the cause of the gait anomaly. The genetic test found a mutation in the KCNC3 gene. The variant c.1268G > A; p.Arg423His was found in a heterozygotic state. This variant is frequently described as a cause for spinocerebellar ataxia type 13 (SCA13) in the literature. Apart from toe walking as the most pronounced symptom, the patient displayed an instable gait with frequent falls and delayed speech development. The genetic test to determine the cause of the gait anomaly successfully diagnosed the patient with a previously undiscovered SCA13 and subsequently enabled the recommendation of personalized further treatment

Genetic Factors Associated with Toe Walking in Children

The article describes genetic factors associated with toe walking in children. Association of gait abnormality with variants in genes listed below is shown: PMP22 (peripheral myelin protein 22), EGR2 (early growth response protein 2), AIFM1 (apoptosis inducing factor mitochondria associated 1), MORC2 (member of the Microrchidia family CW-type zinc finger 2), DHTKD1 (dehydrogenase E1 and transketolase domain containing 1), GDAP1 (ganglioside induced differentiation associated protein 1), KIF1B (kinesin family member 1B), FGD4 (FYVE, RhoGEF and PH domain containing 4), SBF2 (SET binding factor 2), SH3TC2 (SH3 domain and tetratricopeptide repeats 2), NAGLU (N-acetyl-alpha-glucosaminidase), NEFL (neurofilament light) и PRX (periaxin). Genetic testing of patients with toe walking is crucial for accurate diagnostics of this pathology as well as clinical examination

NGS-Panel Diagnosis Developed for the Differential Diagnosis of Idiopathic Toe Walking and Its Application for the Investigation of Possible Genetic Causes for the Gait Anomaly

Idiopathic toe walking (ITW) describes a condition affecting approximately 4.5% of children. Toe walking is an accompanying symptom for many hereditary disorders. This retrospective study uses next-generation sequencing-panel-diagnosis to investigate the feasibility of genetic testing to research the possible genetic causes of ITW and for differential diagnosis. Data were taken from our inhouse database, the minimum age for participants was 3 years. Underlying neurological or orthopaedic conditions were tested for and ruled out prior to diagnosing ITW. Patients, who experienced complications before, during or immediately after birth, children with autism, and patients toe walking less than 50% of the time were excluded. Eighty-nine patients were included in the study, in which 66 (74.2%) patients were boys and 23 (25.8%) girls. Mean age at testing was 7.7 years (range: 3–17 years). Fifteen of the 89 patients included in the study (16.9%) had a genetic variant identified as likely pathogenic or pathogenic by the genetics laboratory. Additionally, we found 129 variants of uncertain significance. About 65.2% of patients showed a pes cavus foot deformity, 27% of patients reportedly had at least one relative who also displayed the gait anomaly, and 37.1% had problems with their speech development. Despite the limitations of the sample size and the scope of our genetic testing targets, our results indicate that research into the genetic causes of ITW could better our understanding of the causes of ITW in otherwise healthy children, to help develop novel methods to detect serious conditions early. ITW could be an early onset symptom for further hereditary conditions