McArdle's disease: A differential diagnosis of idiopathic toe walking.

Idiopathic toe walking (ITW) is a pathological gait pattern in which children walk on their tip toes with no orthopedic or neurological reason. Physiological characteristics of the gastrocnemius muscles, the Achilles tendon, and the foot of toe walkers differ from subjects with a plantigrade walking pattern. McArdle's disease is characterized by the inability to break down muscle glycogen. It is an autosomal-recessive condition, characterized by low exercise tolerance, muscular atrophy at the shoulder girdle, episodes of myoglobinuria after vigorous physical activities and the occurrence of the second wind phenomenon. The aim of this review is to present the case studies of two subjects who were originally diagnosed as idiopathic toe walkers, but were then found to have McArdle's disease. This review will describe some physical characteristics that distinguish McArdle´s disease from Idiopathic toe walkers.

Literature Review of Idiopathic Toe Walking: Etiology, Prevalence, Classification, and Treatment.

PURPOSE: The main objective of this review is to gather the information available about idiopathic toe walking (ITW), its prevalence and classification, and possible therapeutic approaches. In addition, this review aims to clarify the differences between idiopathic toe walkers and tiptoe walkers with underlying neurological or muscle deficiency as primary conditions. Understanding its causes and learning to make a differential diagnosis will help determine the adequate therapeutic approach. METHODS: This is a review of different articles and case studies from 1967 to 2016. The information was gathered to update and unify all the information about ITW that has been published. CONCLUSION: The literature offers limited research regarding the possible etiology, prevalence, classification, and evaluation of ITW. This review puts together all the information regarding the etiology, prevalence, classifications, evaluation, and treatment of ITW. LEVELS OF EVIDENCE: Level IV.

Falso diagnóstico de caminador en puntillas de pies; sospecha de enfermedad de McArdle / False diagnosis of idiopathic toe walker (ITW); suspicion of McArdle disease

El caminar en puntillas de los pies es una condición patológica en la cual las personas caminan en las puntas de los pies sin presentar ninguna condición ortopédica o neurológica. Se ha encontrado que los caminadores en puntillas de pies presentan diferentes características en los músculos gastrocnemios, el tendón de Aquiles y en el pie. La enfermedad de McArdle es una condición médica autosómica recesiva caracterizada por la baja tolerancia a la actividad física, la atrofia de los músculos de la cintura escapular y, en algunos casos, con episodios de mioglobinuria después de realizar ejercicio vigoroso. Este reporte explica el caso de una paciente diagnosticada como caminadora idiopática en puntillas de pies, pero con los signos clínicos de la enfermedad de McArdle. Este reporte busca comentar las características clínicas que diferencian a los caminadores idiopáticos en puntillas de pies y a los pacientes con la enfermedad de McArdle.

Idiopathic Toe Walking is a pathological condition in which the gait takes place on the tip toes. ITW is diagnosed on the absent of any orthopedic or neurological condition. The physiological characteristics of the gastrocnemios muscles, the Achilles tendon, and the foot of Idiopathic toe walkers are different to individuals that are not affected by toe walking. McArdle disease is a medical autosomal-recessive condition, characterised by low exercise tolerance, muscular atrophy at the shoulder girdle, and in some cases myoglobinuria episodes have been reported after vigorous physical activities. In this case study we present a patient diagnosed as Idiopathic toe walker, but with the clinical characteristics of McArdle diseases. The aim of this case study is to present the clinical characteristics that differentiate these two pathological conditions.

Analysis of Physiological Gait Pattern in Children Without the Influence of Footwear.

In the literature, there have been several studies that have analyzed and explained the characteristics of physiological gait in association with pathologies; however, finding information about normal gait pattern while barefoot is difficult. This study focuses on the differences in the barefoot gait between children and adolescents. A total of 320 healthy children and adolescent were recruited and divided into groups according to age: G1 (1-6 years), G2 (7-10 years), G3 (>11 years). Data were collected using a dynamometric platform and analyzed using SPSS software. This study's findings indicate that there are differences in the swing, stance, load, and single support phases of gait. To our knowledge, this is the first study to present the values of standardized data on barefoot gait pattern in children aged from 2 to 10 years. LEVELS OF EVIDENCE: Diagnostic, Level IV: Case series.

The 3-Step Pyramid Insole Treatment Concept for Idiopathic Toe Walking.

The idiopathic toe walking (ITW) gait pattern is characterized in children for walking since the beginning on their first steps on the forefoot; however, these children are able to support their whole foot on the ground. ITW can only be diagnosed in the absence of any orthopaedic or neurological condition known to cause tiptoe walking. The aim of this article is to review other references and provide an outline of the different treatment options, including the 3-step-pyramid insole treatment concept for children with ITW. METHODS: Fifty-four articles in English, German, and Spanish were reviewed. There were comparative, retrospective or case studies, classifications or literature reviews and they were divided according with these categories. All the literature reviewed was published between 2000 and 2015. RESULTS: There are some studies that proved the 3-step pyramid insole treatment concept as an effective option compared with other therapeutic modalities such as physical therapy, casting, botolinum toxin type A (BTX), and surgery. CONCLUSION: There is a wide spectrum regarding the therapeutic options for children with ITW, from physical therapy to surgery options. However, any of these treatment modalities have been reported to be fully successful for the whole toe walking population. Some procedures seem to have achieved faster results or seem to have longer lasting effects. Therefore, further research on the causes of ITW is recommended. LEVELS OF EVIDENCE: Therapeutic, Level II: Systematic review, prospective, comparative.

Idiopathic Toe Walking: Family Predisposition and Gender Distribution.

UNLABELLED: Current literature is inconsistent concerning the causes and the frequency of idiopathic toe walking (ITW). Available studies vary widely in their results. The aim of this study is to supply gender-related data particularly regarding the genetic influence on toe walking. Methods The ITW patterns of 836 children were recorded and analyzed during a period of 4 years. Questionnaires and clinical measurements were evaluated along with clinical tests, assessing the occurrence and severity of toe walking. Information about the incidence of toe-walkers in the family was recorded. Results Of the 836 toe-walkers, 64% were boys and 42% had a positive family history (PF-TW). About 60% of the PF-TW children had fathers with a positive toe-walking pattern. PF-TW children were on average half a year younger than children with a negative family predisposition (NF-TW). Conclusions This study shows that a genetic component might be factor in toe walking. PF-TW children were more severely affected in all performed clinical tests than NF-TW children. LEVELS OF EVIDENCE: Prognostic, Level IV.

Idiopathic Toe Walking: Tests and Family Predisposition.

UNLABELLED: The aim of this study is to provide clinical examination methods that were designed specifically to assess the level of severity among children with idiopathic toe walking (ITW). The idiopathic toe-walking pattern of 836 children was recorded and analyzed during 4 years. Questionnaires and clinical measurements were evaluated, along with differential tests, assessing the occurrence and severity of toe walking. Questions about family history and onset of toe walking were evaluated along with special tests and measurements assessing the occurrence and severity of toe walking. The different measurements apply during this study, ankle dorsiflexion, lumbar lordosis angle, as well as the clinical spin test, walking after spin test, and heel walking test revealed in all cases that children with a positive family predisposition were significantly more affected than children with negative family predisposition. It is concluded that children with ITW and a positive family predisposition were more intensively affected during all performed clinical tests than children with no family predisposition. The tests used during this study have not being used by any other researches, even though they showed significant differences between the children with ITW and children with a normal gait pattern. LEVELS OF EVIDENCE: Diagnostic, Level II: development of diagnostic test with consecutive patients and control patients.

Plantar Static Pressure Distribution in Healthy Individuals: Percentiles for the Evaluation of Forefoot Loading.

In literature, one finds little scientific statements regarding plantar static pressure distribution in healthy individuals. Miscellaneous studies, however, characterize pathologies of feet and associate those with abnormal static or dynamic plantar load sharing. Our study reveals that healthy individuals show significant age-dependent differences in forefoot and rear foot load measured in standing position. The forefoot and rear foot load of 238 female and 193 male individuals aged between 2 and 69 years were measured. Using a pressure distribution measurement platform, the measurements were taken barefooted in standing position. Those measurements are presented as percentage of the overall load. The measurements within the age groups A1 (2-6 years), A2 (7-10 years), and A3 (11-69 years) showed significantly different forefoot loading means of the left foot (A1, 19.9%; A2, 28.2%; A3, 39.7%) and the right foot (A1, 22.6%; A2, 29.7%; A3, 39.6%). The forefoot loadings are graphically displayed as a function of the percentiles 5, 10, 25, 50, 75, 90, and 95. Forefoot loadings are referred to as "prominent" if the measured values lie off the interquartile range; if either below the percentile 10 or above 90 the loadings are referred to as "very prominent." Our study contains significant data regarding the extent of the static load sharing of the forefoot and rear foot of healthy individuals; the data are suited for being standard values to evaluate plantar load sharing. LEVELS OF EVIDENCE: Diagnostic Level IV: Case series.

Ultrafine mapping of Dyscalc1 to an 80-kb chromosomal segment on chromosome 7 in mice susceptible for dystrophic calcification.

In mice, dystrophic cardiovascular calcification (DCC) is controlled by a major locus on proximal mouse chromosome 7 named Dyscalc1. Here we present a strategy that combines in silico analysis, expression analysis, and extensive sequencing for ultrafine mapping of the Dyscalc1 locus. We subjected 15 laboratory mouse strains to freeze-thaw injury of the heart, and association with respective genotypes allowed condensation of the Dyscalc1 locus to 1 Mb. Within this region, 51 known and predicted genes were studied in DCC-susceptible C3H/He and DCC-resistant C57BL/6 mice with respect to mRNA expression in response to injury. Five genes displayed differential expression. Genotyping of seven novel single nucleotide polymorphisms (SNPs) within these genes revealed an 80-Kb region in NZB mice that were found positive for calcification though carrying otherwise alleles from DCC-resistant mice. This microheterogeneity in NZB mice was evolutionary conserved in all DCC-susceptible mouse strains and contains the genes EMP-3, BC013491, and Abcc6 (partially). The flanking SNPs are rs3703247 and NT_039420.5_2757991. mRNA levels of EMP-3 were found to be upregulated in response to injury in both C57BL/6 and C3H/He mice. Sequencing of EMP-3 revealed an SNP leading to an amino acid substitution (p.T153I) that was found in all mouse strains susceptible for DCC but not in resistant strains such as C57BL/6 mice. Thus, the p.T153I changes might affect the biological function of EMP-3 gene product after injury. Using this combined approach, we ultrafine-mapped the Dyscalc1 locus to an 80-Kb region and identified EMP-3 as a new candidate gene for DCC.

Association of a functional polymorphism in the CYP4A11 gene with systolic blood pressure in survivors of myocardial infarction.

OBJECTIVE: Survivors of myocardial infarction (MI) are known to have a high prevalence of arterial hypertension which, at the same time, imposes a major risk to such patients. Genetic variants of the arachidonic acid monooxygenase CYP4A11 may result in decreased synthesis of 20-hydroxyeicostatetraenoic acid (20-HETE), experimental hypertension and elevated blood pressure levels in humans. The present study aimed to investigate the impact of the functionally relevant T8590C polymorphism of this gene on blood pressure and the prevalence of hypertension in MI patients. METHODS: Survivors of MI from the MONICA Augsburg MI registry (n = 560) were studied after a mean of 5.6 years after the acute event. Participants were examined by standardized anthropometric and echocardiographic measurements, as well as genotyping for CYP4A11 T8590C allele status. RESULTS: Genotype frequencies in MI patients (TT = 71.8%, CT = 26.2%, CC = 2.0%) did not differ from those in population-based controls (n = 1363; TT = 75.4%, CT = 22.5% and CC = 2.1%, P = 0.22). MI survivors with the CC genotype displayed higher systolic blood pressure levels (CC: 143.4 +/- 4.9 mmHg versus CT: 134.5 +/- 1.3 mmHg and TT: 131.1 +/- 0.8 mmHg; P = 0.02) and a non-significant trend towards higher diastolic blood pressure levels (CC: 88.4 +/- 3.0 mmHg versus CT: 84.9 +/- 0.8 mmHg and TT: 83.9 +/- 0.5 mmHg; P = 0.17) in multivariate models. Accordingly, the C allele was related to elevated odds ratios for hypertension in a recessive [4.14; 95% confidence interval (CI) = 1.07-15.96, P = 0.04] and in a dominant model (1.50; 95% CI = 1.03-2.20, P = 0.04), respectively. No blood pressure-independent association of the T8590C polymorphism with echocardiographic parameters of left ventricular function and/or geometry was found. CONCLUSION: The data obtained in the present study strengthen the evidence of an association of the CYP4A11 T8590C polymorphism with blood pressure levels and hypertension prevalence. Particularly, the risk of arterial hypertension is substantially higher in MI patients homozygous for the CC allele. By contrast, no evidence was obtained for an association between this genotype and MI.