Abnormal interlimb coordination of motor developmental delay during infant crawling based on kinematic synergy analysis.

BACKGROUND: Previous studies have reported that abnormal interlimb coordination is a typical characteristic of motor developmental delay (MDD) during human movement, which can be visually manifested as abnormal motor postures. Clinically, the scale assessments are usually used to evaluate interlimb coordination, but they rely heavily on the subjective judgements of therapists and lack quantitative analysis. In addition, although abnormal interlimb coordination of MDD have been studied, it is still unclear how this abnormality is manifested in physiology-related kinematic features. OBJECTIVES: This study aimed to evaluate how abnormal interlimb coordination of MDD during infant crawling was manifested in the stability of joints and limbs, activation levels of synergies and intrasubject consistency from the kinematic synergies of tangential velocities of joints perspective. METHODS: Tangential velocities of bilateral shoulder, elbow, wrist, hip, knee and ankle over time were computed from recorded three-dimensional joint trajectories in 40 infants with MDD [16 infants at risk of developmental delay, 11 infants at high risk of developmental delay, 13 infants with confirmed developmental delay (CDD group)] and 20 typically developing infants during hands-and-knees crawling. Kinematic synergies and corresponding activation coefficients were derived from those joint velocities using the non-negative matrix factorization algorithm. The variability accounted for yielded by those synergies and activation coefficients, and the synergy weightings in those synergies were used to measure the stability of joints and limbs. To quantify the activation levels of those synergies, the full width at half maximum and center of activity of activation coefficients were calculated. In addition, the intrasubject consistency was measured by the cosine similarity of those synergies and activation coefficients. RESULTS: Interlimb coordination patterns during infant crawling were the combinations of four types of single-limb movements, which represent the dominance of each of the four limbs. MDD mainly reduced the stability of joints and limbs, and induced the abnormal activation levels of those synergies. Meanwhile, MDD generally reduced the intrasubject consistency, especially in CDD group. CONCLUSIONS: These features have the potential for quantitatively evaluating abnormal interlimb coordination in assisting the clinical diagnosis and motor rehabilitation of MDD.

Mutations obstructing ATP's emplacement in KIF2A nucleotide-binding pocket causes parenchymal malformations, motor developmental delay, with intellectual disability.

BACKGROUND: KIF2A-related tubulinopathy (MIM: #615411) is a very rare disorder that was clinically characterized as microcephaly, epilepsy, motor developmental disorder (MDD), and various malformations of cortical development, but intellectual disability (ID) or global developmental delay (GDD) was rarely reported in the patients. METHODS: Quad whole-exome sequencing (WES) was performed on the proband, the older brother, and their parents. Sanger sequencing was used to verify the candidate gene variant. RESULTS: The proband, a 23-month-old boy, was previously diagnosed with GDD, and his brother, aged nine years, had ID; both were born to a healthy couple. Quad-WES detected a novel heterozygous KIF2A variant, c.1318G>A (p.G440R), in both the brothers but not in the parents. In-silico analysis revealed that the variants G440R and G318R (which were previously reported in the only reported patient with GDD) lead to markedly enlarged side chains and hinder ATP's emplacement in the NBD pocket. CONCLUSIONS: The type of KIF2A variants that sterically hinder ATP emplacing in KIF2A NBD pocket may be associated with the intellectual disability phenotype; however, further studies are needed. Findings in this case also suggest a rare parental germline mosaicism of KIF2A G440R.

A case report of mitochondrial enoyl-CoA hydratase short chain 1 deficiency caused by enoyl-CoA hydratase short chain 1 gene mutation / 中华神经科杂志

Objective:To summarize the clinical features and gene mutation characteristics of a child with mitochondrial enoyl-CoA hydratase short chain 1 deficiency (ECHS1D) caused by enoyl-CoA hydratase short chain 1 ( ECHS1) gene mutation. Methods:The clinical characteristics and genetic test results of a child with ECHS1D who visited the Department of Neurology of Xuzhou Children′s Hospital in January 2021 were retrospectively analyzed, and the clinical features of the disease were also reviewed by searching relevant domestic and foreign literature.Results:The child was a 6 months and 4 days old male, with acute onset, the main clinical manifestation being limb movement disorder after admission. The child had slow motor development, his head was still upright and cannot turn over, the child also cannot sit alone, follow up and make a laugh, and the muscle tension of limbs was increased. The child′s blood lactate was increased to 6.2 mmol/L, which suggested metabolic acidosis, and magnetic resonance imaging (MRI) of the head showed abnormal signals in the basal ganglia on both sides, abnormal enhancement of the meninges of the left cerebral hemisphere. Whole exome sequencing revealed that the child had compound heterozygous mutations in ECHS1 gene, c.563C>T (p.A188V) and c.5C>T (p.A2V), respectively. The child′s father carried c.563C>T mutation, the mother carried c.5C>T mutation, all of which were missense mutations. Conclusions:ECHS1 gene mainly has missense mutations, most of which are compound heterozygous mutations, and a few are homozygous mutations. The ECHS1D caused by ECHS1 gene mutation often affects infants and young children. MRI suggests abnormal signals in the basal ganglia; for cases with the above clinical manifestations and abnormal signals in the basal ganglia on MRI, genetic testing should be considered to confirm the diagnosis.

Changes in the social-emotional functioning of young children with a significant cognitive and motor developmental delay across a two-year period.

Children with a significant cognitive and motor developmental delay (SDD) are vulnerable for the development of (future) behavioral and mental health problems. To support children within this target group, knowledge on their social-emotional development is necessary. Therefore, in this paper, an explorative assessment of the changes in the social-emotional functioning of children with SDD over a two-year period was done. Yearly semi-structured interviews with one or more primary caregiver(s) of 25 children were conducted and analyzed on 13 domains of social-emotional functioning, according to an adapted version of the Scale for Emotional Development - Revised (SED-R). This study showed a lot of variation in individual and group patterns of change across the two-year period. Charting the social-emotional development in this target group is challenging and requires further in-depth analysis of individual trajectories as well as more fine-grained and long-term data collection.

The social-emotional functioning of young children with a significant cognitive and motor developmental delay.

Children with a significant cognitive and motor developmental delay (SDD) are vulnerable for the development of (future) behavioral and mental health problems. This paper aims to assess the social-emotional functioning of these children, both globally and in various domains. Semi-structured interviews with one or more primary caregiver(s) of 45 children were conducted and analyzed on 13 domains of social-emotional functioning, according to the Scale for Emotional Development - Revised (SED-R). The SED-R scoring system was slightly adapted in the current study in order to elucidate more subtle differences between children. A general delayed social-emotional development was found, with children functioning within different phases across domains and certain domains generally showing higher or lower scores. To capture the emotional needs of children with SDD, a more disaggregated scoring system seems valuable so that both the global level and the level per domain can be taken in consideration in designing interventions.

Clinical and biochemical footprints of inherited metabolic disease. V. Cerebral palsy phenotypes.

Cerebral palsy is the most common physical disability of childhood describing a heterogeneous group of neurodevelopmental disorders that cause activity limitation, but often are accompanied by disturbances of sensation, perception, cognition, communication and behavior, or by epilepsy. Inborn errors of metabolism have been reported in the literature as presenting with features of cerebral palsy. We reviewed and updated the list of metabolic disorders known to be associated with symptoms suggestive of cerebral palsy and found more than 150 relevant IEMs. This represents the fifth of a series of articles attempting to create and maintain a comprehensive list of clinical and metabolic differential diagnosis according to system involvement.

'We can't do it alone': Perceived social support in parents of children with a significant cognitive and motor developmental delay.

BACKGROUND: It is generally acknowledged that parent social support is an important target for intervention. To explore the specific needs of parents of young children with a significant cognitive and motor developmental delay (SDD), we aim to chart the sources and perceived sufficiency of the social support they receive. METHOD: Within the context of a broader project, 42 parents of a young child with SDD filled out a questionnaire on contextual factors, including information on social support. RESULTS: The majority of parents reported to receive (more than) sufficient support. Insufficiency is primarily reported with regard to practical support. Apart from the partner, grandparents of the child were the most common source of support. CONCLUSIONS: This study confirms the importance of professional support and work-life balance within this specific target group. Specific attention for practical support needs seems warranted considering the high basic care needs of these children.

Early diagnosis of MECP2 duplication syndrome: Insights from a nationwide survey in Japan.

This study aimed to elucidate the clinical characteristics of MECP2 duplication syndrome (MDS), particularly at initial presentation, and to provide clinical clues for the early diagnosis of this condition. We conducted a nationwide survey for MDS by sending questionnaires to 575 hospitals where board-certified pediatric neurologists were working and 195 residential hospitals for persons with severe motor and intellectual disabilities in Japan. This survey found 65 cases of MDS, and clinical data of 24 cases in which the diagnosis was genetically confirmed were analyzed. More than half of the patients (52%) had visited a hospital at least once during infancy due to symptoms associated with MDS, with a median age at the initial visit of 7 months. The symptoms that were frequently prevalent at the first visit were facial dysmorphic features, hypotonia, motor developmental delay, and recurrent infections. Dysmorphic features included small mouth, tented upper lip, tapered fingers, and hypertelorism. Other symptoms, including epilepsy, intellectual disabilities, autistic features, stereotypic movements, and gastrointestinal problems, generally appeared later with age. Some symptoms of MDS were found to be age-dependent and may not be noticeable in infancy. Recognition of these clinical characteristics may facilitate the early diagnosis and proper treatment of patients with MDS, improve their long-term outcomes, and help adapt appropriate genetic counseling.

Bosley-Salih-Alorainy syndrome in patients from India.

Bi-allelic HOXA1 pathogenic variants clinically manifest as two distinct syndromes, Bosley-Salih-Alorainy syndrome (BSAS) and Athabascan brainstem dysgenesis syndrome, mainly reported in two different populations from Saudi Arabia and southwest North America, respectively. Here we report two siblings of Indian origin with BSAS phenotype caused by a novel homozygous exon 2 HOXA1 pathogenic variants.

Inter-Limb Muscle Synergies and Kinematic Analysis of Hands-and-Knees Crawling in Typically Developing Infants and Infants With Developmental Delay.

Hands-and-knees-crawling is an important motor developmental milestone and a unique window into the development of central nervous system (CNS). Mobility during crawling is regularly used in clinical assessments to identify delays in motor development. However, possible contribution from CNS impairments to motor development delay is still unknown. The aim of this study was to quantify and compare inter-limb muscle synergy and kinematics during crawling among infants at a similar developmental age, however, clinically determined to be typically developing (TD, N = 20) infants, infants at risk of developmental delay (ARDD, N = 33), or infants with confirmed developmental delay (CDD, N = 13). We hypothesized that even though all of the groups are at a similar developmental age, there would be differences in kinematic measures during crawling, and such differences would be associated with CNS impairment as measured by electromyography (EMG) features. Surface EMG of eight arm and leg muscles and the corresponding joint kinematic data were collected while participants crawled on hands and knees at their self-selected velocity. Temporal-spatial parameters and normalized Jerk-Cost (JC) function (i.e., smoothness of movement) were computed from the measured kinematics. The inter-limb muscle synergy and the number of co-activating muscles per synergy were measured using EMGs. We found that the infants with CDD demonstrated higher normalized JC values (less movement smoothness), fewer muscle synergies, and more co-activating muscles per synergy, compared to infants with TD (p < 0.05) and ARDD (p < 0.05). Furthermore, the normalized JC values were correlated (p < 0.05) with the number of co-activation muscles per synergy. Our results suggest a constrained neuromuscular control strategy due to neurological injury in infants with CDD, and such constrain may contribute to the reduced movement smoothness in infant crawling.

Kinematics and Surface Electromyography of Upper Limbs in Motor-delayed Children and Normal Children in Crawling Stage / 中国康复理论与实践

Objective To detect kinematics and surface electromyography (sEMG) of upper limbs in normal children and motor-delayed children for clinical assessment. Methods From December, 2015 to June, 2016, twelve healthy children and thirteen children with motor de-velopmental delay less than two years old were analyzed kinematics with Motion Analysis system and sEMG. Results The angle of motion of right shoulder was more in the motor-delayed children than in the normal children (t=2.576, P<0.05). The difference of root mean square values of bilateral triceps brachii was more in the motor-delayed children than in the normal ones (t=2.448, P<0.05). Conclusion Detecting kinematics and sEMG may supply information for early personalized treatment strategy.

Comparative Evaluation between Diameter Difference of the Thumb and Asymmetry of Lateral Cerebral Ventricles in Children with Developmental Delay: A New Finding.

OBJECTIVE: Anthropometry (measurement of body dimensions) has been used for clinical diagnosis of growth and developmental disorders during pregnancy and after birth. Different brain volumes have also been shown in abnormal developmental disorders. This study compares the different horizontal diameters of the left- and right-hand thumbnails and asymmetry of lateral cerebral ventricles in children with developmental delays. MATERIALS & METHODS: This retrospective case control study was carried out in the Pediatric Neurologic Outpatient of a university hospital in Tehran, Iran (2009-2011). Twenty-eight patients with motor developmental disorders (case) and 28 healthy individuals (control) had brain MRIs and volume of lateral cerebral ventricles size had been studied. The maximum horizontal diameters of the left and right thumbnails were measured by calipers during physical and neurological exams by a pediatric neurologist. Finally, we compared and analyzed different horizontal diameters of the left and right hand thumbnails and asymmetry of lateral cerebral ventricles. RESULTS: There was a significant correlation between asymmetry of brain lateral ventricles size and mean difference of horizontal diameter of thumb nails (P = 0.0001). A meaningful relation between brain hemispheres asymmetry and developmental delay (P = 0.04) was seen. CONCLUSION: The asymmetry of thumbnails can be a marker for asymmetry of lateral ventricles and child developmental delays.

Vestibular dysfunction is a clinical feature of the Jervell and Lange-Nielsen Syndrome.

OBJECTIVES: To investigate the possible association between Jervell and Lange-Nielsen Syndrome (JLNS) genotype and vestibular dysfunction. DESIGN: In 15 cases with JLNS, clinical data obtained from a semi-structured interview and full medical records were reviewed and post-rotatory nystagmus testing was performed. RESULTS: All genotyped cases (n = 14) had double KCNQ1 mutations. Symptoms of impaired balance were reported in 14/14 deaf JLNS cases. Gross motor developmental delay (not walking without support at 18 months of age) was seen in 11/12 cases with available data (mean age for walking: 24 months). A pathologic post-rotatory test was seen in 9/9 tested subjects, and in 3 subjects clinical testing had been performed showing complete lack of vestibular function. Vestibular dysfunction was seen in deaf JLNS cases with (n = 5) and without (n = 9) cochlear implants, including subjective symptoms (5/5 vs. 9/9) and gross motor developmental delay (5/5 vs. 6/8). CONCLUSIONS: We identified a high frequency of symptoms and signs associated with vestibular dysfunction in deaf JLNS cases, irrespective of previous cochlear implantation. Disruption of endolymph homeostasis in the inner ear, including cochlea and vestibular system, by profound KCNQ1 function loss is the proposed mechanism.

A clinical study on Duchenne muscular dystrophy

No abstract available.