Motor Developmental Milestones Research Articles

Familial and genetic association with neurodevelopmental disorders caused by a heterozygous variant in the SRRM2 gene.

Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function, characterized by an inability to reach cognitive, emotional, and motor developmental milestones. The pathology of NDDs is complex. A recent study found that variants in the SRRM2 gene cause NDDs. However, genetic conditions play the most important role in the etiology of NDD. The genetic causes of NDD are extremely heterogeneous, leading to certain challenges in clinical diagnosis. A pregnant woman with congenital intelligence disorder came to our hospital for genetic diagnosis to predict the status of her fetus. Her mother and a brother also suffer from congenital intelligence disorder. She has a daughter with speech delay. Whole exome sequencing was used to identify a mutation (c.1415C>G) in the SRRM2 gene of this family that resulted in a change in the 472nd amino acid residue of the SRRM2 protein from serine to terminated. We report a family with an autosomal dominant genetic disorder caused by variants in the SRRM2 gene causing NDDs. Prenatal diagnosis can help patients with this genetic disorder to have healthy offspring.

Phenotype Genotype Characterization of FKRP-related Muscular Dystrophy among Indian Patients.

The phenotypic spectrum of Fukutin-related protein (FKRP) mutations is highly variable and comprises of limb girdle muscular dystrophy (LGMD) R9 (previously LGMD 2I) and FKRP related congenital muscular dystrophies. To identify the distinct genotype phenotype pattern in Indian patients with FKRP gene mutations. We retrospectively reviewed the case files of patients with muscular dystrophy having a genetically confirmed FKRP mutation. All patients had undergone genetic testing using next-generation sequencing. Our patients included five males and four females presenting between 1.5 years and seven years of age (median age - 3 years). The initial symptom was a delayed acquisition of gross motor developmental milestones in seven patients and recurrent falls and poor sucking in one patient each. Two patients had a language delay, with both having abnormalities on the brain MRI. Macroglossia, scapular winging, and facial weakness were noted in one, three and four patients respectively. Calf muscle hypertrophy was seen in eight patients and ankle contractures in six. At the last follow-up, three patients had lost ambulation (median age - 7 years; range 6.5-9 years) and three patients had not attained independent ambulation. Creatine kinase levels ranged between 2793 and 32,396 U/L (mean 12,120 U/L). A common mutation - c.1343C>T was noted in 5 patients in our cohort. Additionally, four novel mutations were identified. Overall, six patients had an LGMD R9 phenotype, and three had a congenital muscular dystrophy phenotype. Patients with FKRP mutations can have varied presentations. A Duchenne-like phenotype was the most commonly encountered pattern in our cohort, with c.1343C>T being the most common mutation.

Pregnancy, pregnancy outcomes, and infant growth and development after recovery from Ebola virus disease in Liberia: an observational cohort study

Minimal data exist on pregnancy following recovery from Ebola in people of child-bearing potential (females aged roughly 18-45 years). The aim of this study was to assess viral persistence or reactivation in pregnancy, the frequency of placental transfer of anti-Ebola IgG antibodies, and pregnancy outcomes in this population. In this observational cohort study, we studied self-reported pregnancies in two groups: seropositive people who had recovered from Ebola virus disease (seropositive group) and seronegative people who had close contact with people with Ebola (seronegative group). Participants had enrolled in the PREVAIL III longitudinal study and were exposed during the 2014-2016 Liberian Ebola outbreak. The primary outcome was pregnancy result. We assessed rates of livebirths and other pregnancy results in both study groups, and presence of Ebola RNA by PCR in samples of placenta, maternal and cord blood, breastmilk, and vaginal secretions from people who had recovered from Ebola who conceived a median of 14 months after acute Ebola virus disease. Mixed-model logistic regression evaluated associations between first-reported pregnancy outcome, age, and study group. Growth and neurodevelopment in the infants born to people in the seropositive group were assessed at 6-month intervals for 2 years. Data were accrued by PREVAIL III study staff. 1566 participants were enrolled between June 17, 2015, and Dec 14, 2017, of whom 639 became pregnant (215 seropositive, 424 seronegative) and 589 reported pregnancy outcomes (206 seropositive, 383 seronegative). 105 infants born to 98 mothers in the seropositive group were enrolled in the birth cohort. Ebola RNA was not detected in 205 samples of placenta, cord blood, or maternal blood taken at birth from 54 mothers in the seropositive group, nor in 367 vaginal swabs. Viral RNA was found in two of 354 longitudinal breastmilk samples. All but one of 57 infants born during these 54 births were seropositive for anti-Ebola antibodies. Neonates showed high concentrations of anti-Ebola IgG, which declined after 6 months. Odds of adverse pregnancy outcome among the two groups were indistinguishable (OR 1·13, 95% CI 0·71-1·79). Compared with WHO standards, infants born to those in the seropositive group had lower median weight and length, and larger median head circumference over 2 years. Compared with a cohort from the USA accrual of gross motor developmental milestones was similar, whereas attainment of pincer grasp and early vocalisation were mildly delayed. The risks of Ebola virus reactivation in the peripartum and postpartum period and of adverse birth outcomes are low in those who have recovered from Ebola virus disease and become pregnant approximately 1 year after acute Ebola virus disease. The implication for clinical practice is that care of people who are pregnant and who have recovered from Ebola can be offered without risks to health-care providers or stigmatisation of the mothers and their offspring. The implication for prospective mothers is that safe pregnancies are entirely possible after recovery from Ebola. National Institute of Allergy and Infectious Diseases and Liberia Ministry of Health.

Contributions of Screen Use on Early Language and Development Milestones in Argentinean Toddlers from Different Socioeconomic Contexts

The objective of the following research was to describe the use of digital media (i.e., TV, background TV, cell phone, PC, and Tablet), presence of the adults during this activity, and its association with language, motor, and language developmental milestones and SES in the first years of life. Participants were 114 primary caregivers of toddlers between 12 and 36 months (M = 27.48 months, SD = 7.31, female = 58, low SES = 56). Parental reports of infant media use, motor and language development milestones, the Inventory of Skills Development (CDI), and the INDEC Scale (for SES) were used. The results showed that, on average, toddlers engaged for 1 h per day with TV and were passive recipients of background TV for 2 h a day, which was the most used screen. In addition, parents tend to share TV with toddlers. Language positively related with child Tablet use, book use, and TV shared with an adult, and there were negative associations with children’s cell phone and PC use alone and with an adult. For SES, having at least one basic need unsatisfied or less parental educational and occupancy was related with more background TV and use, less time sharing this type of media with toddlers, and less use and quantity of books at home. In general, there were no relations between digital media use and developmental milestones. This indicates that the excessive use of screens could relate to some early language skills, although it is necessary to investigate the context in which they are used.

Hypermanganesemia with Dystonia Type 2: A Rare Entity. (P12-11.001)

<h3>Objective:</h3> NA <h3>Background:</h3> Hypermanganesemia with dystonia type 2 is an established, rare autosomal recessive partially reversible neurodegenerative condition characterised by mutations in the SLC39A14 gene. Manganese deposition in such cases has a special predilection for the basal ganglia structures leading to dystonia and parkinsonian features. We report such a case of hypermanganesemia in a 1 year old child presenting with extrapyramidal features. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 1 year old female child presented with regression of developmental milestones for the past 2 months, losing the ability to stand or even sit without support—skills that she had previously acquired at an appropriate time. This was associated with dystonic posturing of her neck and limbs for the last 1 month. Cognitive skills were normal as per her age without any history of convulsions or other systemic features. Her birth and family history were unremarkable. Her neurological examination was remarkable only for generalised dystonia of her limbs, neck and trunk. Magnetic resonance imaging was suggestive of paramagnetic substance deposition in bilateral basal ganglia and dentate nucleus. Normal routine blood parameters were followed by extensive investigations to rule out Wilson’s disease, NBIA and other autoimmune pathologies. Her blood manganese levels were significantly elevated and her genetic sequencing revealed compound heterozygous mutations of the SLC39A14 gene at exons 7 and 8. She was started on chelation therapy with Penicillamine and oral iron. Dystonia resolved significantly by the end of 6 months of therapy with marked improvement in her motor developmental milestones. <h3>Conclusions:</h3> Hypermanganesemia with dystonia type 2 (HMNDYT2) is a rare genetic disorder characterised by neuronal manganese deposition without other systemic features. This case highlights the importance of recognising this potentially rare treatable condition and with adequate chelation therapy at the right time, near total restoration of motor symptomatology is possible. <b>Disclosure:</b> Dr. Bhattacharya has nothing to disclose. Dr. Chintha has nothing to disclose. Dr. Biswas has nothing to disclose. Dr. Das has nothing to disclose. Dr. Chakraborty has nothing to disclose. Dr. Mukherjee has nothing to disclose.

Early Motor Developmental Milestones and Personality Traits in Midlife: A 50-Year Follow-Up Study

Background The purpose of this study was to investigate if infants' age at attaining motor developmental milestones is associated with the big five personality traits 50 years later. Methods Mothers of 8395 infants from the Copenhagen Perinatal Cohort recorded a total of 12 motor developmental milestones during the first year of their infant's life. Information on at least one milestone was available for 1307 singletons with adult follow-up scores on the NEO-Five-Factor Inventory. The mean age at personality testing was 50.1 years. Results Slower attainment of motor milestones was associated with increased neuroticism and lower conscientiousness in midlife. All 12 motor developmental milestones explained a total of 2.4% of the variance in neuroticism, while they explained 3.2% of the variance in conscientiousness. These results remained significant after adjustment for the included family and perinatal covariates, as well as adult intelligence. Discussion The personality trait of neuroticism is a general risk factor for psychopathology and has in young adulthood been found to be associated with early motor development. However, evidence on associations of motor developmental milestones with other personality traits has been non-existent. These findings suggest that delays in early motor development may not only characterise individuals with later psychopathology, including schizophrenia, but may also be associated with personality traits such as neuroticism and conscientiousness through the life course.

Exclusive Breastfeeding Measured by Deuterium-Oxide Turnover Method is Associated with Motor Development in Rural Senegalese Infants

BackgroundThe findings on the relationship between breastfeeding and children’s motor development are very poor, particularly in low and middle income countries, because of the use of inadequate measures of breastfeeding practices. ObjectivesTo assess the relationship between exclusive breastfeeding, measured by the deuterium-oxide turnover method (DTM), and the acquisition of motor development in a cohort of Senegalese children. MethodsOne hundred forty mother-infant (4–5 mo) pairs were recruited and monitored up to 18 mo. Breast milk intake and breastfeeding practices were measured by DTM. Six stages of motor development were assessed: “sitting without support,” “hands-and-knees crawling,” “standing with assistance,” “walking with assistance,” “standing alone,” and “walking alone.” Acquisition age of motor milestones between exclusively breastfed (EBF) and not exclusively breastfed (non-EBF) infants was compared using Student’s and Wilcoxon’s tests. Mixed linear regression, adjusted with confounding factors, was used to determine the association between EBF and motor development. ResultsOverall, 32.9% of infants were EBF at the enrollment at 4–5 mo of age. Breast milk intake of EBF infants was significantly higher than that of non-EBF infants (1039 ± 193 g/d compared with 915 ± 211 g/d; P < 0.01). At 4–5 mo of age, only “sitting without support” (67.4% compared with 47.9%, P = 0.02) and “hands-and-knees crawling” (17.4% compared with 4.3%, P = 0.01) were completed significantly in the EBF group. At 18 mo, all children had completed all 6 motor developmental milestones. However, their acquisition age was significantly earlier in the EBF group after adjustment. Non-EBF infants had a delay of 0.4 to 0.5 mo on the acquisition of the first 5 stages compared to EBF infants. For “walking alone,” no difference was found after adjustment. ConclusionsMotor skill acquisition is earlier in EBF infants compared to non-EBF infants. This finding highlights the need to strengthen the advocacy for EBF up to 6 mo.

A novel homozygous SLC39A14 variant in an infant with hypermanganesemia and a review of the literature.

Manganese (Mn) is an essential trace metal necessary for good health; however, excessive amounts in the body are neurotoxic. To date, three genes (SLC30A10, SLC39A8, and SLC39A14) have been discovered to cause inborn errors in Mn metabolism in humans. As very rare diseases, the clinical features require further clarification. A male Chinese patient who mainly presented with hypermanganesemia and progressive parkinsonism-dystonia was recruited for this study. We collected and analyzed clinical information, performed whole-exome sequencing (WES), and reviewed the relevant literature. The motor-developmental milestones of the patient were delayed at the age of 4 months, followed by rapidly progressive dystonia. The patient displayed elevated Mn concentrations in blood and urine, and brain magnetic resonance imaging (MRI) showed symmetrical hyperintensity on T1-weighted images and hypointensity on T2-weighted images in multiple regions. A novel homozygous variant of the SLC39A14 gene (c.1058T > G, p.L353R) was identified. The patient was treated with disodium calcium edetate chelation (Na2CaEDTA). Three months later, mild improvement in clinical manifestation, blood Mn levels, and brain MRI was observed. To date, 15 patients from 10 families have been reported with homozygous mutations of SLC39A14, with a mean age of onset of 14.9 months. The common initial symptom is motor regression or developmental milestone delay, with a disease course for nearly all patients involving development of progressive generalized dystonia and loss of ambulation before treatment. Additionally, hypermanganesemia manifests as Mn values ranging from 4- to 25-fold higher than normal baseline levels, along with brain MRI results similar to those observed in the recruited patient. Nine SLC39A14 variants have been identified. Seven patients have been treated with Na2CaEDTA, and only one patient achieved obvious clinical improvement. We identified a novel SLC39A14 mutation related to autosomal recessive hypermanganesemia with dystonia-2, which is a very rare disease. Patients present motor regression or delay of developmental milestones and develop progressive generalized dystonia. Chelation therapy with Na2CaEDTA appears to effectively chelate Mn and increase urinary Mn excretion in some cases; however, clinical response varies. The outcome of the disease was unsatisfactory. This study expands the genetic spectrum of this disease.

Zoledronic Acid Treatment in Infants and Toddlers with Osteogenesis Imperfecta is Safe and Effective: A Tertiary Care Centre Experience.

Osteogenesis imperfecta (OI) is a genetic disorder of the extracellular matrix of bone characterized by low bone mass manifesting as frequent fractures, delayed motor development, pain, and impaired quality of life. The intravenous bisphosphonate, pamidronate is an established treatment for OI. Recently, zoledronic acid (ZA) has been used for the management of OI. To assess the efficacy and safety of ZA in children below five years of age with OI. A hospital-based prospective observational study. Patients with OI aged less than five years attending our centre were treated with intravenous ZA at a dose of 0.05 mg/kg every six months. Subjects were closely monitored for clinical and biochemical variables, adverse events, and new-onset fractures. The response to therapy was assessed by monitoring clinical variables including the degree of bony pains, number of fractures, height/length standard deviation score (SDS), and motor developmental milestones. All patients were analysed at baseline and at the end of two years for biochemical parameters and clinical severity score (CSS) as proposed by Aglan et al. with modifications. After two years of treatment, OI patients showed a significant decline in the rate of fractures (p < 0.001), improvement in ambulation (p = 0.005), alleviation of pain (p < 0.001), and improvement in height SDS (p < 0.05). There was a significant improvement in CSS after two years of therapy. Apart from mild flu-like symptoms and mild asymptomatic hypocalcaemia immediately post-infusion, no other adverse effect was noted. ZA therapy in infants and children below five years of age with OI was effective and safe and a more convenient alternative to pamidronate.

VACTERL Association in Kano, North-West Nigeria

VACTERL association is a term used to describe the simultaneous occurrence of at least 3 of the following congenital malformations: vertebral anomalies, anal atresia, cardiac malformation, tracheo-oesophageal fistula, renal dysplasia, and limb abnormalities. Most cases occur sporadically with an estimated incidence rate of 1 in 10,000 – 40,000 births. We report the case of an 11-month-old infant that presented with a complaint of recurrent cough and difficulty in breathing since 1 month of life. There is also the history of delayed motor developmental milestones. Physical examination and investigations revealed the presence of VACTERL association (bilateral talipes equinovarus deformity, multiple cardiac shunt lesions, and malformation of the 5th lumbar vertebrae with dural ectasia and lumbosacral scoliosis). She has been on oral diuretics and is currently on follow-up in pediatric cardiology, orthopedic, and neurosurgery clinics. This case report highlights the presence of a rare case of the VACTERL association in Kano, North-West Nigeria.

Congenital chloride diarrhea presenting as dilated fetal bowel loops.

Congenital chloride diarrhea presenting as dilated fetal bowel loops.

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.

Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial

Risdiplam is an orally administered therapy that modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene and is approved for the treatment of spinal muscular atrophy. The FIREFISH study is investigating the safety and efficacy of risdiplam in treated infants with type 1 spinal muscular atrophy versus historical controls. The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support for at least 5 s after 12 months of treatment. Here, we report on the safety and efficacy of risdiplam in FIREFISH part 2 over 24 months of treatment. FIREFISH is an ongoing, multicentre, open-label, two-part study. In FIREFISH part 2, eligible infants (aged 1-7 months at enrolment, with a genetically confirmed diagnosis of spinal muscular atrophy, and two SMN2 gene copies) were enrolled in 14 hospitals in ten countries across Europe, North America, South America, and Asia. Risdiplam was orally administered once daily at 0·2 mg/kg for infants between 5 months and 2 years of age; once an infant reached 2 years of age, the dose was increased to 0·25 mg/kg. Infants younger than 5 months started at 0·04 mg/kg (infants between 1 month and 3 months old) or 0·08 mg/kg (infants between 3 months and 5 months old), and this starting dose was adjusted to 0·2 mg/kg once pharmacokinetic data were available for each infant. The primary and secondary endpoints included in the statistical hierarchy and assessed at month 12 have been reported previously. Here we present the remainder of the secondary efficacy endpoints that were included in the statistical hierarchy at month 24: the ability to sit without support for at least 30 s, to stand alone, and to walk alone, as assessed by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale. These three endpoints were compared with a performance criterion of 5% that was defined based on the natural history of type 1 spinal muscular atrophy; the results were considered statistically significant if the lower limit of the two-sided 90% CI was above the 5% threshold. FIREFISH is registered with ClinicalTrials.gov, NCT02913482. Recruitment is closed; the 36-month extension period of the study is ongoing. Between March 13 and Nov 19, 2018, 41 infants were enrolled in FIREFISH part 2. After 24 months of treatment, 38 infants were ongoing in the study and 18 infants (44% [90% CI 31-58]) were able to sit without support for at least 30 s (p<0·0001 compared with the performance criterion derived from the natural history of untreated infants with type 1 spinal muscular atrophy). No infants could stand alone (0 [90% CI 0-7]) or walk alone (0 [0-7]) after 24 months of treatment. The most frequently reported adverse event was upper respiratory tract infection, in 22 infants (54%); the most common serious adverse events were pneumonia in 16 infants (39%) and respiratory distress in three infants (7%). Treatment with risdiplam over 24 months resulted in continual improvements in motor function and achievement of developmental motor milestones. The FIREFISH open-label extension phase will provide additional evidence regarding long-term safety and efficacy of risdiplam. F Hoffmann-La Roche.

New results for risdiplam in spinal muscular atrophy

Spinal muscular atrophy type 1 is a severe, progressive neuromuscular disease with symptom onset before age 6 months. Without disease modifying therapy, infants usually die of respiratory failure before age 2 years. Previous results from the FIREFISH study, an open-label clinical trial of risdiplam in patients with type 1 or infantile onset spinal muscular atrophy, have indicated that oral risdiplam might be safe and efficacious when given over 12 months to children with this type of spinal muscular atrophy. In The Lancet Neurology, Riccardo Masson and colleagues 1 Masson R Mazurkiewicz-Bełdzińska M Rose K et al. Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. Lancet Neurol. 2022; (published online Oct 13.)https://doi.org/10.1016/S1474-4422(22)00339-8 Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar report the results of secondary analyses from FIREFISH, including safety and efficacy data at 24 months. These analyses clearly show that patients continued to benefit from up to 24 months of treatment, with attainment of motor milestones not seen in untreated patients in natural history studies. Furthermore, the safety profile seen at 12 months was maintained at 24 months. Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trialTreatment with risdiplam over 24 months resulted in continual improvements in motor function and achievement of developmental motor milestones. The FIREFISH open-label extension phase will provide additional evidence regarding long-term safety and efficacy of risdiplam. Full-Text PDF

Asociación entre el uso de medios electrónicos, hitos del desarrollo y lenguaje en infantes

The use of electronic media has increased in early childhood. During early childhood, language and motor skills are important for the development of other cognitive skills. Therefore, it becomes essential to study how the use of screens is associated with these important skills in the first years of life. The objective of the following research was to describe the use of electronic media (i. e., TV, cellphone and tablet) and its association with language and developmental milestones in the first years of life. Participants were 253 primary caregivers of infants between 2 to 48 months (M = 30.17 months, SD = 10.82, female = 124). Parental reports of infant media use, motor and language development milestones, the MacArthur-Bates Communicative Development Inventory (CDI) and the Permanent Household Survey (EPH) for sociodemographic variables were used. The results showed that, on average, infants began to use screens during the first year of life at an average of one hour per day with TV as the most used medium and video viewing as the activity they did the most. The number of hours of devices usage was positively associated with lexical density and sentence use. Furthermore, starting device use at a later age was associated with lower scores in language reports and later milestones of motor and language development. No differences were found based on the type of device content and sociodemographic variables. Results indicate that the excessive use of screens could affect some early skills, although it is necessary to investigate the context in which they are used. https://doi.org/10.16888/interd.2022.39.3.9

Duration of Exclusive Breastfeeding for Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis.

Cessation of exclusive breastfeeding (EBF) with early introduction of complementary food provides additional calories for catch-up growth but may also increase the risk of adverse outcomes. The objective of this study was to assess effects of exclusive breastfeeding for less than 6 months compared with 6 months in preterm and low birth weight infants. Data sources include Medline, Scopus, Web of Science, CINAHL, and Index Medicus through June 30, 2021. Study selection includes randomized trials and observational studies. Primary outcomes were mortality, morbidity, growth, and neurodevelopment. Data were extracted and pooled using random-effects models. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias of included studies. A total of 2 studies of 307 preterm or low birth weight infants were included. None of the study results could be pooled. Both studies compared EBF for 4 months to 6 months. Growth was similar between the 4-month and 6-month EBF groups for the following outcomes: weight-for-age z-score at corrected age 12 months (mean [standard deviation], 4-month group: -1.7 [1.1], 6-month group: -1.8 [1.2], 1 study, 188 participants, low certainty evidence), absolute weight gain (gram) from 16 to 26 weeks of age (4-month group: 1004 [366], 6-month group: 1017 [350], 1 study, 119 participants, very low certainty evidence), and linear growth gain (cm) from 16 to 26 weeks of age (4-month group: 4.3 [0.9], 6-month group: 4.5 [1.2], 1 study, 119 participants, very low certainty evidence). There were no apparent differences in reported morbidity symptoms. No difference in the timing to achieve motor development milestones between the 2 groups was found (1 study; 119 participants, very low certainty evidence). A limited number of studies prevented data pooling. The evidence is very uncertain about the effect of exclusive breastfeeding for less than 6 months for preterm and low birth weight infants. Further studies are warranted to better answer this question.

Improving Recognition of Treatable Rare Neuromuscular Disorders in Primary Care: A Pilot Feasibility Study.

Innovative targeted treatments for neuromuscular disorders (NMDs) can dramatically improve the course of illness. Diagnostic delay, however, is a major impediment. Here, we present a pilot project aimed at assessing the feasibility of a screening program to identify children at high risk for NMDs within the first 30 months of life. The Promoting Early Diagnosis for Neuromuscular Disorders (PEDINE) project implemented a three-step sequential screening in an area of about 300,000 people with (1) an assessment of the motor development milestones to identify “red flags” for NMDs by primary care pediatricians (PCPs) as part of the routine Health Status Check visits; (2) for the children who screened positive, a community neuropsychiatric assessment, with further referral of suspected NMD cases to (3) a hospital-based specialized tertiary care center. In the first-year feasibility study, a total of 10,032 PCP visits were conducted, and twenty children (0.2% of the total Health Status Check visits) screened positive and were referred to the community neuropsychiatrist. Of these, four had elevated creatine kinase (CK) serum levels. This pilot study shows that screening for NMDs in primary care settings is feasible and allows children at high risk for muscular disorder to be promptly identified.

D1 MTE2 Case 6: A child with metabolic myopathy

A 15-year-old boy, born to 3rd degree consanguineously married couple presented with complaints of abnormal waddling gait and outward bowing of legs since 1-year, joint pains and difficulty in climbing stairs since 6 months. Had normal developmental motor milestones and was of average height compared to peers. No h/o muscle pains. There was no symptomatic relief with vitamin D supplementation. On examination child had large low set ears, mal aligned teeth with widened wrists and ankles, double malleoli and genu varum. There was also evidence of proximal myopathy in the lower limbs. Initial investigations revealed serum calcium of 10.6 mg/dl, Po4 of 2 mg/dl, ALP 3322 IU/L, vitamin D3 10.2 ng/ml and serum PTH of 1448 pg/ml.

POSC8 Burden of Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency in Italian Patients from Symptomatology and Motor Development Perspective

AADC deficiency is an ultrarare genetic disorder affecting monoamine production, and causing a mix of non-specific motor, cognitive and autonomic symptoms that often complicates diagnosis. Patient characteristics in the literature are poorly described and geographically biased. The aim of this study was to describe the burden of AADC deficiency in Italy focusing on patient symptoms and developmental motor milestones.

Improved Motor Function With Risdiplam in Infants With Type 1 SMA

Improved Motor Function With Risdiplam in Infants With Type 1 SMA