Acquisition Of Motor Milestones Research Articles

Early childhood practitioners’ awareness of gross motor milestone acquisition and movement guidelines

Background: Early childhood development (ECD) practitioners are essential in governing foundational aspects, such as gross motor development and participation in physical movement.Aim: This study aimed to determine ECD practitioners in Vanderbijlpark’s awareness of gross motor milestone acquisition and movement guidelines for children birth to 4 years. Associations between these ECD practitioners’ demographic aspects and their determined awareness were also explored.Setting: This study included 50 ECD practitioners (M = 36.9 years) from nine ECD Centres (ECDCs) in Vanderbijlpark, South Africa.Methods: A descriptive quantitative, cross-sectional design was followed. Data was collected using a self-administered questionnaire. Data analysis included descriptive statistics and associations between practitioners’ demographic aspects and their awareness of gross motor milestone acquisition and movement guidelines.Results: Correct awareness of gross motor milestone acquisition was mainly observed for milestones acquired during the first year of life. Participants’ awareness of screen time guidelines was relatively good, while their awareness of movement and sleep guidelines was poor. Having children, as well as the age of these children, respectively, correlated significantly with practitioners’ knowledge of standing alone (p = 0.007) and jumping 2 feet (p = 0.046). Participants’ work experience or training was not significantly associated with their determined awareness.Conclusion: The sample of ECD practitioners in Vanderbijlpark, South Africa, did not have adequate awareness of gross motor milestones and recommended movement guidelines for children birth to 4 years.Contribution: Limited awareness of gross motor milestone acquisition and movement guidelines amongst ECD practitioners’ warrants development of knowledge through ECD-related training, CPD opportunities, and short courses.

Associations between early language, motor abilities, and later autism traits in infants with typical and elevated likelihood of autism.

Slower acquisition of language and motor milestones are common in infants with later autism and studies have indicated that motor skills predict the rate of language development, suggesting these domains of development may be interlinked. However, the inter-relationships between the two domains over development and emerging autistic traits are not fully established. We studied language and motor development using standardized observational and parent-report measures in infants with (n = 271) and without (n = 137) a family history of autism across four waves of data collection from 10 to 36 months. We used Random Intercept Cross-Lagged Panel Models to examine contemporaneous and longitudinal associations between language and motor developments in both elevated and typical likelihood groups. We estimated paths between language and motor abilities at 10, 14, 24, and 36 months and autism trait scores at 36 months, to test whether the domains were interrelated and how they related to emerging autism traits. Results revealed consistent bidirectional Expressive Language (EL) and Fine Motor (FM) cross-lagged effects from 10 to 24 and a unidirectional EL to FM effect from 24 to 36 months as well as significantly correlated random intercepts between Gross motor (GM) and Receptive language (RL), indicating stable concurrent associations over time. However, only the associations between GM and RL were associated with later autism traits. Early motor and language are linked, but only gross motor and receptive language are jointly associated with autistic traits in infants with an autism family history.

"I Am Afraid of Positioning my Baby in Prone": Beliefs and Knowledge about Tummy Time Practice.

To identify beliefs and knowledge about tummy time (TT) practice and its repercussions on motor development. Longitudinal study carried out with parents/caregivers of infants older than 30 days of life. Two assessments were performed. A structured interview was conducted, while the babies were between one and six months old to identify beliefs, knowledge about TT, and the motor milestone achievement expected for the age. At six to 12 months, the risk of motor development delay was tracked using the survey of well-being of young infant questionnaire (SWYC). 41 families responded to the SWYC questionnaire (21 were allocated to the TT group). 31.70% reported that it was not important to put the infants in a prone position while awake, and 70.70% said they are afraid their babies would become breathless when positioned in a prone position. 85.70% of infants from the TT group showed typical development, while 55% of the control group showed atypical development for their age (p = 0.01). Only three infants from the control group were at risk of delayed motor development (p = 0.10). Most of the families feel insecure about proning their babies and fear breathlessness when positioned. Acquisition of motor milestones prevailed in the TT group, suggesting an association between TT practice and motor milestone achievement.

Motor Outcome Measures in Pediatric Patients with Congenital Muscular Dystrophies: A Scoping Review

Congenital muscular dystrophies (CMDs) are a heterogeneous group of genetic neuromuscular disorders. They usually occur at birth or in early childhood, with delayed acquisition of motor milestones, and diffuse muscle weakness. A dystrophic pattern is evident on the muscle biopsy. They are highly variable both in terms of severity and clinical evolution and in terms of pathogenetic biochemical mechanisms. The aim of this review is to collect and summarize the current knowledge of motor function in pediatric patients with congenital muscular dystrophies and the instruments used to assess it. This scoping review was conducted using the methodology of PRISMA (extension for Scoping Reviews, PRISMA-ScR). Two databases were queried from January 2002 to November 2022. Articles were identified based on title and abstract. Full-text papers published in peer-reviewed English-language journals were selected. It emerged that motor functional aspects are still underinvestigated in CMD patients, probably due to the rarity of these conditions and the phenotypic variability. The scales used to assess motor function are heterogeneous, as are the age groups considered. Finally, the predominant type of research design is cross-sectional; few studies analyze the progression of motor function over time. All these factors make it difficult to correlate the results of different publications and stress the need for more accurate and shared protocols for assessing motor function in these patients.

Pelizaeus-Merzbacher disease-like disorder in an Indian girl with a missense variant in GJC2 gene

Pelizaeus-Merzbacher-like disease 1 (PMLD1) is a slowly progressive leukodystrophy that typically presents during the neonatal or early infantile period with nystagmus, commonly associated with hypotonia, delayed acquisition of motor milestones, speech delay and dysarthria. We present a 7-year-old female born to a nonconsanguineous marriage with developmental delay. On examination, she had 22 teeth, and nystagmus with pseudophakia. Neurological examination showed spasticity with increased deep tendon reflexes. On investigation, MRI of the brain done at 3 years showed hypomyelination. Targeted exome sequencing revealed a homozygous non-synonymous variation c.138C>G in exon 2 of the GJC2 gene. Sanger sequencing was done which showed the presence of a variant in the heterozygous state in both parents. PMLD1 should be suspected in any child presenting with diffuse hypomyelination with abnormal eye movements, especially in a girl child with PelizaeusMerzbacher disease phenotype with hypomyelination in the pons.

Therapeutic Options for the Management of Pompe Disease: Current Challenges and Clinical Evidence in Therapeutics and Clinical Risk Management.

Pompe disease is a genetic disorder produced by mutations in the GAA gene leading to absence or reduced expression of acid alpha-glucosidase, an enzyme that metabolizes the breakdown of glycogen into glucose. There are two main phenotypes, the infantile consisting of early onset severe weakness and cardiomyopathy, and the adult which is characterized by slowly progressive skeletal and respiratory muscle weakness. Enzymatic replacement therapy (ERT) has been available for Pompe disease for more than 15 years. Although the treatment has improved many aspects of the disease, such as prolonged survival through improved cardiomyopathy and acquisition of motor milestones in infants and slower progression rate in adults, ERT is far from being a cure as both infantile and adult patients continue to progress. This fact has prompted the development of improved or new enzymes and other treatments such as gene therapy or substrate reduction strategies. Here, we review the data obtained from randomized clinical trials but also from open-label studies published so far that have assessed the advantages and limitations of this therapy. Moreover, we also review the new therapeutic strategies that are under development and provide our opinion on which are the unmet needs for patients with this disease.

The associations between stunting and wasting at 12 months of age and developmental milestones delays in a cohort of Cambodian children

Worldwide, over 250 million children under 5 years do not reach their developmental potential due to several causes, including malnutrition. In Cambodia, the prevalence of stunting and wasting among children remains high. This prospective cohort study aimed to assess acquisition of motor and cognitive developmental milestones in early childhood and their associations with stunting and wasting. Children aged from 0 to 24 months were recruited from three provinces in Cambodia and followed up to seven times from March 2016 to June 2019, until their 5 years. Data collection included anthropometry and developmental milestones. Seven motor and seven cognitive milestones were evaluated using the Cambodian Development Milestone Assessment Tool. Associations were assessed with parametric survival models. Hazard ratios (HR) below 1 stood for lower probabilities for achieving developmental milestones. Data were available for 7394 children. At 12 months, the prevalence of stunting and wasting were 23.7% and 9.6% respectively. Both were consistently associated with delays in most motor and cognitive milestones. Stunting was strongly associated with delays in gross motor milestones (HR < 0.85; p < 0.001). Wasting was more strongly associated with delays in fine motor development and most cognitive milestones (HR < 0.75; p < 0.001). Promoting nutritional programs in the first 1000 days to prevent malnutrition is essential to further the optimal growth and motor and cognitive development of Cambodian children.

A novel TRMT5 mutation causes a complex inherited neuropathy syndrome: The role of nerve pathology in defining a demyelinating neuropathy.

We aim to present data obtained from three patients belonging to three unrelated families with an infantile onset demyelinating neuropathy associated to somatic and neurodevelopmental delay and to describe the underlying genetic changes. We performed whole-exome sequencing on genomic DNA from the patients and their parents and reviewed the clinical, muscle and nerve data, the serial neurophysiological studies, brain and muscle MRIs, as well as the respiratory chain complex activity in the muscle of the three index patients. Computer modelling was used to characterise the new missense variant detected. All three patients had a short stature, delayed motor milestone acquisition, intellectual disability and cerebellar abnormalities associated with a severe demyelinating neuropathy, with distinct morphological features. Despite the proliferation of giant mitochondria, the mitochondrial respiratory chain complex activity in skeletal muscle was normal, except in one patient in whom there was a mild decrease in complex I enzyme activity. All three patients carried the same two compound heterozygous variants of the TRMT5 (tRNA Methyltransferase 5) gene, one known pathogenic frameshift mutation [c.312_315del (p.Ile105Serfs*4)] and a second rare missense change [c.665 T > C (p.Ile222Thr)]. TRMT5 is a nuclear-encoded protein involved in the post-transcriptional maturation of mitochondrial tRNA. Computer modelling of the human TRMT5 protein structure suggests that the rare p.Ile222Thr mutation could affect the stability of tRNA binding. Our study expands the phenotype of mitochondrial disorders caused by TRTM5 mutations and defines a new form of recessive demyelinating peripheral neuropathy.

Introduction of Complementary Foods for Children with Down Syndrome: Parent and Physician Experiences

Aims Children with Down syndrome are at risk for feeding difficulties due to medical comorbidities and associated developmental delays, yet there are no peer-reviewed published standards to guide families with feeding progression. This study explored family experiences introducing complementary foods (e.g., purees, table food) for children with Down syndrome. A secondary aim was to describe primary care provider (PCP) training on early progression of feeding for children with Down syndrome and investigate the recommendations they gave families. Methods Semi-structured interviews with twenty-two parents and eight primary care providers (PCPs) were conducted. Descriptive statistics were used to characterize the sample and to report on findings related to feeding milestones. Qualitative interview data were considered in an iterative and cyclical fashion. Results Parental themes included differences in feeding for children with Down syndrome, limited guidance that was not always followed, feeding difficulties and related stress, and gross motor milestone acquisition related to feeding milestones. PCP themes included limited resources/training, providing similar recommendations for children with and without Down syndrome, and desire for training/resources. Conclusions Published guidelines on feeding progression for children with Down syndrome are needed, including considerations for determining when skill and interest converge to signal safe introduction of complementary foods.

The relationship between motor milestone achievement and childhood motor deficits in children with Attention Deficit Hyperactivity Disorder (ADHD) and children with Developmental Coordination Disorder

BackgroundThe prevalence of motor impairment is high in ADHD, but we do not know if this stems from infancy. Aims1) to compare the acquisition of motor milestones across three groups: Typically Developing (TD), Attention Deficit Hyperactivity Disorder (ADHD) and Developmental Coordination Disorder (DCD); 2) to determine the relationship between current motor ability and ADHD characteristics in children with ADHD. Methods and proceduresThe parents of children aged 8–16 years (ADHD, N = 100; DCD, N = 66; TD, N = 40) completed three online questionnaires: Motor milestone questionnaire; Developmental Coordination Disorder Questionnaire (DCDQ’07) (concurrent motor ability); Conners 3 Parent Rating Scale Long Form (ADHD characteristics). Outcome and resultsWhen considered as a group, the ADHD group achieved motor milestones within a typical timeframe, despite concurrent motor impairments. Motor ability was not associated with ADHD characteristics. Latent Profile Analysis demonstrated that 56 % of the ADHD group and 48 % of the DCD group shared the same profile of motor milestone achievement, concurrent motor ability and ADHD characteristics. Outcomes and conclusionsUnlike children with DCD, the motor impairment often observed in ADHD is not evident from infancy. It is also not part of the ADHD phenotype. Individual differences analysis demonstrated the broad heterogeneity of the ADHD phenotype.

Gene therapy for spinal muscular atrophy: hope and caution

In the past decade major advances have been made in the treatment of spinal muscular atrophy, a devastating, progressive motor neuron disease caused by a deficiency in the SMN protein due to a mutation in the SMN1 gene. Several approaches aimed at increasing production of the SMN protein have been developed. The intrathecal antisense oligonucleotide nusinersen and an oral small molecule risdiplam (approved by the US Food and Drug Administration and the European Medicines Agency) target splicing of the paralogous gene SMN2, hence improving the production of the functional SMN protein. Onasemnogene abeparvovec is a one-time AAV-9-based gene transfer therapy, introducing a full copy of the SMN1 gene. Approval was based on data from the START study, 1 Mendell JR Al-Zaidy S Shell R et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017; 377: 1713-1722 Crossref PubMed Scopus (936) Google Scholar reporting an unprecedented survival rate at 24 month follow-up and unexpected acquisition of motor milestones in 12 patients with infantile-onset spinal muscular atrophy type 1, the most severe type of the disease, which is characterised by a poor prognosis with short life expectancy. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trialResults from this multicentre trial build on findings from the phase 1 START study by showing safety and efficacy of commercial grade onasemnogene abeparvovec. Onasemnogene abeparvovec showed statistical superiority and clinically meaningful responses when compared with observations from the PNCR natural history cohort. The favourable benefit–risk profile shown in this study supports the use of onasemnogene abeparvovec for treatment of symptomatic patients with genetic or clinical characteristics predictive of infantile-onset spinal muscular atrophy type 1. Full-Text PDF

Vestibular Dysfunction and Gross Motor Milestone Acquisition in Children With Hearing Loss: A Systematic Review.

To describe the impact of vestibular dysfunction on gross motor development in children with hearing loss. MEDLINE (PubMed), Embase (Elsevier), Web of Science (Clarivate), and the Cumulative Index of Nursing and Allied Health Literature (EBSCO). A systematic review was reported in concordance with the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses). Articles on children with hearing loss who underwent at least 1 instrumented measure of vestibular function and had gross motor milestones assessed were included. The Downs and Black checklist was used to assess risk of bias and methodological quality. Eleven articles were included in the systematic review. Three articles stratified quantitative results of gross motor milestone acquisition by severity of vestibular impairment. Over half of studies were case series published within the last 5 years. This systematic review showed that children with hearing loss and severe, bilateral vestibular dysfunction demonstrate delayed gross motor milestones. However, it was difficult to draw conclusions on whether milder forms of vestibular dysfunction significantly affect gross motor milestone acquisition in children with hearing loss. The reason is that most studies were of low to moderate quality, used different assessment methods, and contained results that were descriptive in nature. This emerging area would benefit from future research, such as higher-quality studies to assess vestibular function and gross motor milestones. This would allow for better characterization of the impacts of vestibular impairment, especially milder forms, in children with hearing loss.

Transcriptional subtyping explains phenotypic variability in genetic subtypes of autism spectrum disorder.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by deficits in social communication and presence of restricted, repetitive behaviors, and interests. However, individuals with ASD vary significantly in their challenges and abilities in these and other developmental domains. Gene discovery in ASD has accelerated in the past decade, and genetic subtyping has yielded preliminary evidence of utility in parsing phenotypic heterogeneity through genomic subtypes. Recent advances in transcriptomics have provided additional dimensions with which to refine genetic subtyping efforts. In the current study, we investigate phenotypic differences among transcriptional subtypes defined by neurobiological spatiotemporal co-expression patterns. Of the four transcriptional subtypes examined, participants with mutations to genes typically expressed highly in all brain regions prenatally, and those with differential postnatal cerebellar expression relative to other brain regions, showed lower cognitive and adaptive skills, higher severity of social communication deficits, and later acquisition of speech and motor milestones, compared to those with mutations to genes highly expressed during the postnatal period across brain regions. These findings suggest higher-order characterization of genetic subtypes based on neurobiological expression patterns may be a promising approach to parsing phenotypic heterogeneity among those with ASD and related neurodevelopmental disorders.

Kinetic parameters during land and water walking performed by individuals with Down Syndrome

BackgroundDown Syndrome (DS) is a genetic condition presenting delay in acquisition of main motor milestones, such as walking. Although studies have been investigating the biomechanical parameters during land walking performed by individual with DS, the literature is scarce regarding kinetic parameters analysis in this population, specially during water walking. Research questionThis study sought to assess the vertical ground reaction force (Fz) of walking performed in water and on land at different speeds by individuals with DS. MethodsFourteen adults with DS (age: 27.9 ± 7.9 years; body mass: 58.4 ± 12.9 kg; height: 1.4 ± 0.1 m, body mass index: 29.2 ± 5.4 kg.m-2) completed two sessions of data collection, one on land and another in aquatic environment. The protocol consisted of walking performed at three self-selected speeds (slow, comfortable and fast) in randomized order. The Fz was assessed with a waterproof force plate in each condition. Two-way repeated-measures ANOVA (environment and speed), with Bonferroni’s post hoc tests, were used for analysis. A significance level was set as α = 0.05. ResultsSignificant differences were observed between environments (p < 0.001), with reduced first peak of Fz (68-73%), second peak of Fz (66-70%), loading rate (75-78%) and impulse (40-41%) in the water walking for all speeds analyzed. In the aquatic environment, no significant difference was observed for the first and second Fz peaks with the increasing speed of walking. Moreover, the loading rate significantly increased (p = 0.019) as the impulse significantly reduced (p < 0.001) in the higher speeds. SignificanceIndividuals with DS present reduced Fz outcomes during water walking in comparison to land. Therefore, water walking may be performed by individuals with DS with safe vertical loads on lower limbs regardless the self-selected speed for rehabilitation, correction of gait and training purposes.

Drug treatment for spinal muscular atrophy type I.

Background Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells of the spinal cord, which leads to progressive muscle weakness. Children with SMA type I will never be able to sit without support and usually die by the age of two years. There are no known efficacious drug treatments that influence the course of the disease. This is an update of a review first published in 2009. Objectives To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA type I, and to assess if such therapy can be given safely. Drug treatment for SMA types II and III is the topic of a separate updated Cochrane review. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE (January 1991 to February 2011), EMBASE (January 1991 to February 2011) and ISI Web of Knowledge (January 1991 to 8 March 2011). We searched the Clinical Trials Registry of the U.S. National Institute of Health (www.ClinicalTrials.gov) (8 March 2011) to identify additional trials that had not yet been published. Selection criteria We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA type I. Participants had to fulfil the clinical criteria and have a deletion or mutation of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis.The primary outcome measure was time from birth until death or full time ventilation. Secondary outcome measures were development of rolling, sitting or standing within one year after the onset of treatment, and adverse events attributable to treatment during the trial period. Data collection and analysis Two authors (RW and AV) independently reviewed and extracted data from all potentially relevant trials. For included studies, pooled relative risks and standardised mean differences were to be calculated to assess treatment efficacy. Main results One small randomised controlled study comparing riluzole treatment to placebo for 10 SMA type 1 children was identified and included in the original review. No further trials were identified for the update in 2011. Regarding the primary outcome measure, three of seven children treated with riluzole were still alive at the ages of 30, 48 and 64 months, whereas all three children in the placebo group died; but the difference was not statistically significant. Regarding the secondary outcome measures, none of the children in the riluzole or placebo group developed the ability to roll, sit or stand, and no adverse effects were observed. For several reasons the overall quality of the study was low, mainly because the study was too small to detect an effect and because of baseline differences. Follow-up of the 10 included children was complete. Authors' conclusions No drug treatment for SMA type I has been proven to have significant efficacy.

Clinical Evidence Supporting Early Treatment Of Patients With Spinal Muscular Atrophy: Current Perspectives.

Recent advances in the treatment of spinal muscular atrophy (SMA) have dramatically altered prognosis. Rather than a rapidly lethal disease, SMA type 1, the most severe form with the earliest onset of SMA, has become a disease in which long-term event-free survival with the acquisition of important motor milestones is likely. Prognosis for patients with SMA type 2 has shifted from slow and progressive deterioration to long-term stability. Nevertheless, there is a large heterogeneity in terms of clinical response to currently available treatments, ranging from absence of response to impressive improvement. The only factor identified that is predictive of treatment success is the age of the patient at the initiation of treatment, which is closely related to disease duration. The aim of this paper is to review available evidence that support early intervention using currently available treatment approaches.

Provision of low-iron micronutrient powders on alternate days is associated with lower prevalence of anaemia, stunting, and improved motor milestone acquisition in the first year of life: A retrospective cohort study in rural Ethiopia.

Inappropriate complementary feeding contributes to growth faltering, anaemia, and cognitive impairments. Limited programmatic evidence exists on the effectiveness of low-iron micronutrient powders (MNPs) on anaemia and motor development when provided every other day in the first year of life. This study used an existing demonstration project to evaluate associations between exposure of low-iron MNPs, anaemia, and motor development of infants in Southern Ethiopia. Using a retrospective cohort design, 200 infants aged 9 to 12months (98 MNP exposed; 102 unexposed) were recruited, and data on socio-economic characteristics, anthropometric measures, dietary diversity scores (DDS), haemoglobin concentrations, and motor development acquisition were collected, and MNP exposed and unexposed groups were compared. Logistic regressions were run to identify predictors of acquisition of motor development milestones. Sociodemographic characteristics and dietary diversity scores were similar between MNP exposed and unexposed groups. Provision of low-iron (6mg) MNP every other day, for 3months, was associated with reduced risk of anaemia and stunting and increased achievement of motor development. After adjusting for age, infants exposed to MNPs had a higher likelihood of standing alone (AOR=3.1; 95% CI [1.53, 6.46]) and walking alone (4.9; 95% CI [2.12, 11.37]) than unexposed ones. Exposure to MNPs, DDS, stunting, and mothers education were associated with acquisition of motor development milestones. Provision of low-iron dose MNPs on alternate days is associated with lower prevalence of anaemia, stunting, and increased motor development achievements. Integrating routine monitoring of motor development milestones with growth monitoring and anaemia screening can inform nutrition interventions to support optimal brain development.

Multiple micronutrient supplementation using spirulina platensis and infant growth, morbidity, and motor development: Evidence from a randomized trial in Zambia.

In developing countries, micronutrient deficiency in infants is associated with growth faltering, morbidity, and delayed motor development. One of the potentially low-cost and sustainable solutions is to use locally producible food for the home fortification of complementary foods. This study aimed to test the hypothesis that locally producible spirulina platensis supplementation would achieve the following: 1) increase infant physical growth, 2) reduce morbidity, and 3) improve motor development. We randomly assigned 501 Zambian infants into the control group or the spirulina group. Children in the control group (n = 250) received a soya-maize-based porridge for 12 months; those in the spirulina group (n = 251) received the same food with the addition of spirulina. We assessed the change in infants’ anthropometric status, morbidity (probable pneumonia, cough, probable malaria, and fever), and motor development over 12 months. The baseline characteristics were not different between the two groups. The attrition rate (47/501) was low. The physical growth of infants in the two groups was similar at 12 months of intervention, as measured by height-for-age z-scores and weight-for-age z-scores. Infants in the spirulina group were 11 percentage points less likely to develop a cough (CI: -0.23, -0.00; P < 0.05) and were more likely to be able to walk alone at 15 months (0.96 ± 0.19) than infants in the control group (0.92 ± 0.28). Home-fortification of complementary foods using spirulina had positive effects on upper respiratory infection morbidity prevention and motor milestone acquisition among Zambian infants.

Musculoskeletal anomalies in children with Down syndrome: an observational study

BackgroundMusculoskeletal complications of Down syndrome (DS) are common but infrequently reported. The combination of ligamentous laxity and low muscle tone contributes to increased risk of a number of musculoskeletal disorders...

A novel nonsense PIEZO2 mutation in a family with scoliosis and proprioceptive defect

PIEZO2 mutations have been described in dominant arthrogryposis, but homozygous mutations of PIEZO2 may also be responsible for more complex clinical patterns, associating distal arthrogryposis, neonatal respiratory insufficiency, scoliosis and proprioceptive impairment. We report here two sisters presenting with these clinical and genetic features. They had a similar phenotype, with severe hypotonia and respiratory distress at birth, delayed acquisition of motor milestones and need of scoliosis surgery. Hypotonia and alteration of proprioception were at the forefront of clinical examination for both, along with areflexia, hyperlaxity, cutis laxa, and discrete facial dysmorphy. Electrophysiological studies, including electroneuromyography and sensory evoked potentials, showed a mild sensory axonopathy without any myopathic features, but revealed a peripheral proximal lemniscal defect. Creatine kinase, muscular MRI and biopsy were normal, as well as cerebral MRI and neurometabolic biological explorations. They had a moderate restrictive syndrome on respiratory function tests and cardiac function was normal. Molecular studies performed on a panel of genes involved in distal arthrogryposis disclosed a nonsense homozygous c.3241C > T (p.Arg1051*) mutation in the PIEZO2 gene, which was also present at the heterozygous state in their mother's DNA. This new PIEZO2 mutation was in accordance with the phenotype combining arthrogryposis, scoliosis, hyperlaxity and proprioceptive impairment.