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ABSTRACT Objective We created WiTNNess as a hybrid prospective/cross‐sectional observational study to simulate a clinical trial for infantile‐onset TNNT1 myopathy. Our aims were to identify populations for future trial enrollment, rehearse outcome assessments, specify endpoints, and refine trial logistics. Methods Eligible participants had biallelic pathogenic variants of TNNT1 and infantile‐onset proximal weakness without confounding conditions. The primary endpoint was ventilator‐free survival. “Thriving” was a secondary endpoint defined as the ability to swallow and grow normally without non‐oral feeding support. Endpoints of gross motor function included independent sitting and standing as defined by the Word Health Organization, a novel TNNT1 abbreviated motor score, and video mapping of limb movement. We recorded adverse events, concomitant medications, and indices of organ function to serve as comparators of safety in future trials. Results Sixteen children were enrolled in the aggregate cohort (6 prospective, 10 cross‐sectional; median census age 2.3 years, range 0.5–13.8). Median ventilator‐free survival was 20.2 months and probability of death or permanent mechanical ventilation was 100% by age 60 months. All six children (100%) in the prospective arm failed to thrive by age 12 months. Only 2 of 16 (13%) children in the aggregate cohort sat independently and none stood alone. Novel exploratory motor assessments also proved informative. Laboratory and imaging data suggest that primary manifestations of TNNT1 deficiency are restricted to skeletal muscle. Interpretation WiTNNess allowed us to streamline and economize the collection of historical control data without compromising scientific rigor, and thereby establish a sound operational framework for future clinical trials.

Purpose Developmental delay (DD) is reported to be frequent in developing countries, such as India. Hence, this study was carried out to evaluate preventable risk factors that can predispose children to DD, through observations of pediatric neurology outpatients. Methods This was a prospective, observational, and descriptive cross-sectional single-center hospital-based study for a period of 30 days, split into two separate time periods due to the impact of the coronavirus disease 2019 pandemic. Children who newly presented to the pediatric neurology outpatient department were considered. There were a total of 151 boys and girls, from 6 months to 14 years of age. Detailed demographic information on prenatal, natal and postnatal risk factors relevant to the neurological diagnosis was collected. Antenatal education for mothers about breastfeeding and newborn care, place of delivery, the availability of round-the-clock pediatric care during the delivery, gestational age, maternal fever, encephalitis, seizures, meningitis, blood pressure, gestational diabetes mellitus, infections, history of consanguinity, and genetic disorders were all considered. The data were analyzed with odds ratios and multivariable logistic regression. Results Forty-three of the 151 enrolled children had DD. Significant associations were found between consanguinity and DD (adjusted odds ratio [AOR], 6.50; 95% confidence interval [CI], 1.96 to 21.51; P

Background: Silvery Hair Syndromes (SHS), an autosomal recessive inherited disorder, includes Chediak–Higashi syndrome (CHS), Griscelli syndrome (GS), Hermansky–Pudlak syndrome (HPS), and Elejalde syndrome. Associated immunological and neurological defects and predilection for hemophagocytic lymphohistiocytosis (HLH) makes them a distinctive entity in pediatric practice. Thorough clinical examination, bedside investigations such as peripheral blood smear (PBS) and hair microscopy, and bone marrow (BM) examination are inexpensive and reliable diagnostic tools. Methods: We report 12 cases with SHS (CHS, n = 06; GS, n = 04; HPS, n = 02). Results: 8 out of 12 SHS children (CHS-05, GS-03) presented with HLH. Out of 5 cases of CHS with HLH, 2 died, 3rd is stable post-chemotherapy; 4th completed chemotherapy, underwent matched related hematopoietic stem cell transplant (HSCT), and is stable 8 months off treatment. The 5th child completed chemotherapy and is in process of transplant. One CHS child without HLH is thriving without any treatment. Of the 4 GS cases, 3 presented with HLH and received chemotherapy (HLH 2004 protocol). One lost follow-up after initial remission; another had recurrence 7 months off treatment and discontinued further treatment. The third child had recurrence 1.5 years after initial chemotherapy; HLH 2004 protocol was restarted followed by HSCT from matched sibling donor; is currently well, 2.5 years post-transplant. One child with GS had neurological features with no evidence of HLH and did not take treatment. Of 2 children with HPS, one presented with severe sepsis and the other with neurological problems. They were managed symptomatically. Conclusion: In SHS with HLH, chemotherapy followed by allogeneic hematopoietic stem cell transplantation is a promising curative option.