Neuroimaging to Genotype: Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population.

Several genetic disorders are associated with either a permanent deficit or a delay in central nervous system myelination. We investigated 24 unrelated families (25 individuals) with deficient myelination after clinical and radiological evaluation. A combinatorial approach of targeting and/or genomic testing was employed. Molecular diagnosis was achieved in 22 out of 24 families (92%). Four families (4/9, 44%) were diagnosed with targeted testing and 18 families (18/23, 78%) were diagnosed using broad genomic testing. Overall, 14 monogenic disorders were identified. Twenty disease-causing variants were identified in 14 genes including PLP1, GJC2, POLR1C, TUBB4A, UFM1, NKX6-2, DEGS1, RNASEH2C, HEXA, ATP7A, SETBP1, GRIN2B, OCLN, and ZBTB18. Among these, nine (45%) variants are novel. Fourteen families (82%, 14/17) were diagnosed using proband-only exome sequencing (ES) complemented with deep phenotyping, thus highlighting the utility of singleton ES as a valuable diagnostic tool for identifying these disorders in resource-limited settings.

Metabolic Bone Disease in Children With Transfusion-Dependent Thalassemia.

OBJECTIVE: This study aimed to detect metabolic bone disease and endocrinopathies in a cohort of patients with transfusion-dependent thalassemia (TDT). METHODS: This prospective study was conducted between March 2020 - August 2021. Children with TDT older than 5 years, receiving regular blood transfusion, underwent comprehensive endocrine and metabolic bone disease evaluation, which included screening for short stature, delayed puberty, diabetes mellitus, hypothyroidism, adrenal insufficiency and hypoparathyroidism. Children older than 10 years also underwent. X-ray of thoracolumbar spine, and dual energy X-ray absorptiometry (DXA) scanning. RESULTS: Out of 37 patients (19 males), with mean (SD) age 15 (6) years, hypogonadism was the commonest endocrine deficiency seen in 15 (62%), followed by short stature, abnormal glucose metabolism, subclinical adrenal insufficiency, hypothyroidism, and hypoparathyroidism. Vitamin D insufficiency/deficiency was seen in 12 (60%) and hypocalcemia in 2 patients. Low bone mass was seen in 8, and osteoporosis, as evidenced by vertebral fractures, in 4 patients. Of the four patients with vertebral fracture, three were aged ≤18 years, one was symptomatic, two each had grade 1 and grade 2 fractures, one had multiple vertebral fractures, and all four had hypogonadism and multiple endocrine deficiencies. CONCLUSION: Vertebral fractures occur even in the second decade among patients with TDT, and are often associated with endocrinopathies, most commonly hypogonadism. Early screening and prevention of vertebral fractures is necessary.

Multilocus disease-causing genomic variations for Mendelian disorders: role of systematic phenotyping and implications on genetic counselling.

Multilocus disease-causing genomic variations (MGVs) and multiple genetic diagnoses (MGDs) are increasingly being recognised in individuals and families with Mendelian disorders. This can be mainly attributed to the widespread use of genomic tests for the evaluation of these disorders. We conducted a retrospective study of families evaluated over the last 6 years at our centre to identify families with MGVs and MGDs. MGVs were observed in fourteen families. We observed five different consequences: (i) individuals with MGVs presenting as blended phenotypes (ii) individuals with MGVs presenting with distinct phenotypes (iii) individuals with MGVs with age-dependent penetrance (iv) individuals with MGVs with one phenotype obscured by another more predominant phenotype (v) two distinct phenotypes in different individuals in families with MGVs. Consanguinity was present in eight (8/14, 57.1%) of them. Thirteen families had two Mendelian disorders and one had three Mendelian disorders. The risk of recurrence of one or more conditions in these families ranged from 25% to 75%. Our findings underline the importance of the role of a clinical geneticist in systematic phenotyping, challenges in genetic counselling and risk estimation in families with MGVs and MGDs, especially in highly inbred populations.

Systemic allergic reaction to a caterpillar in a 3-month-old infant.

Systemic reactions to contact with a caterpillar are rare in children. A 3-month-old infant presented to the emergency department with acute onset of rash, severe respiratory distress and shock. Her mother volunteered that the infant had been exposed to a tree processionary caterpillar. The infant responded to systemic corticosteroids and antihistamines although the rash persisted for more than 5 days.

Long-term neurodevelopment outcome of caffeine versus aminophylline therapy for apnea of prematurity.

OBJECTIVE: Methylxanthines are the most commonly prescribed drug in neonatal setups. However, Clinicians show indecision in choosing the right agent for Apnea of Prematurity in most of the developing countries. Present study aimed to compare rate of mortality and survival with normal neurodevelopment outcome at 18 to 24 months of corrected age, between Caffeine- and Aminophylline-treated infants for apnea of prematurity. METHODS: 240 infants were randomly allocated to caffeine and aminophylline for apnea of prematurity during February 2012 to January 2015. Long-term neurodevelopmental assessment was done only from children who had attained corrected age of 18 to 24 months during April 2014 to February 2016. Cognitive, language and motor deficits were assessed by Bayley Scale of infant and toddler development (BSID - III). Postnatal characteristics such as hearing and visual impairments during NICU stay were noted and same were followed up. RESULTS: Infants allocated to caffeine group showed 83% less risk of getting cognitive impairment (RR 0.16; CI 95% range 0.02 to 1.36), 50% less risk of developing motor deficits (RR 0.50; CI 95% range 0.12 to 1.95) and 24% less risk of developing language problems (RR 0.76; CI 95% range 0.36 to 1.58). However in all the neurodevelopment domains the difference between groups was not statistically significant. Risk of mortality in caffeine group was 9% less over aminophylline group which was statistically non-significant (RR - 0.92; CI 95% range - 0.45 to 1.84; p = 0.81). Physical growth parameters were found to be similar in both the groups. Risk of developing visual abnormality and hearing impairments was also statistically non-significant between the groups. CONCLUSION: Caffeine and aminophylline showed similar effects in reducing the rate of mortality and improving the survival without neurodevelopment delays; though the clinical significance of caffeine over aminophylline cannot be undermined.

Predisposing factors, incidence and mortality of pneumothorax in neonates.

AIM: Incidence, risk factors, morbidity and mortality of pneumothorax in neonates vary widely. We aimed to evaluate characteristics, predisposing factors and associated primary lung conditions of pneumothorax in neonates. METHODS: Neonates diagnosed to have pneumothoraces in a neonatal unit of university teaching hospital between May 2006 and August 2008 were studied. Pneumothorax was defined as accumulation of air in the pleural cavity as confirmed by chest radiograph. RESULTS: A total of 25 neonates with pneumothorax were studied. Among them, 32% were inborn, 62% were male and 52% were term neonates. Mean birth weight and median gestation were 2336 g and 37 weeks, respectively. Incidence among inborn neonates was 0.27% and among term and preterm, 0.13% and 0.79%, respectively. Incidence among Neonatal Intensive Care Unit admissions was 1.86%. Ten pneumothoraces occurred in neonates receiving ventilation with an incidence of 1.85%. Incidence of pneumothorax among ventilated neonates was not significantly different from nonventilated (P=0.8). About 84% of pneumothorax occurred within 48 hours of life. Pneumothorax was unilateral in 84% and more common on right side. Underlying pulmonary pathology was observed in 72% and included hyaline membrane disease (HMD) in 40%, meconium aspiration syndrome (MAS) in 24% and pneumonia in 8%. Mean intrapleural drainage was 2.5 days and 9 neonates died. CONCLUSION: Incidence of pneumothorax was similar to reports in the literature and higher among preterm than term neonates. HMD and MAS were common underlying lung conditions for neonatal pneumothorax. Incidence among ventilated neonates was lower than other reports.

Isolated bilateral severe fetal hydrothorax: complete resolution following a single postnatal thoracocentesis.

Isolated pleural effusion is a rare condition in a fetus or neonate with high mortality. When there are no other findings of hydrops fetalis or documented etiology such as inflammatory, iatrogenic or cardiac problems exist, isolated pleural effusion is considered. Timely diagnosis and management not only avoids mortality but also results in excellent prognosis. For fetal hydrothorax, intrauterine management is usually recommended. For those who present late, postnatal management includes intubation, thoracocentesis, ventilation and supportive care. The authors present isolated bilateral severe hydrothorax in a preterm neonate that resulted in severe respiratory compromise at birth. A single postnatal thoracocentesis resulted in complete resolution. No definite etiology for hydrothorax could be established. He had normal growth and development during his follow up till 1 year of age.

Association of indoor air pollution with acute lower respiratory tract infections in children under 5 years of age.

BACKGROUND: Indoor air pollution is an important risk factor for acute lower respiratory tract infections (ALRTI) in developing countries. AIM: To determine the relationship of indoor air pollution with ALRTI in children under 5 years of age. METHODS: A prospective, case-control study of risk factors, particularly indoor air pollution, for developing ALRTI in children under 5 years of age was conducted in Udupi District Hospital. The WHO definition of ALRTI was used. Healthy children attending immunisation services were enrolled as controls. Data pertaining to important factors causing indoor air pollution such as cooking fuel other than liquid petroleum gas (LPG) and passive smoking were collected along with potential socio-demographic factors and nutrition in both groups and analysed. RESULTS: A total of 202 children including 101 cases and 101 controls were studied. The proportions of infants (1-12 months) among cases and controls were 62.4% and 71.3%, respectively. Of those with ALRTI, 24.8% had pneumonia, 45.5% had severe pneumonia and 29.7% had very severe disease. Exposure to passive smoking was not associated with ALRTI. Cooking fuel other than LPG was significantly associated with ALRTI (OR 26.3, 95% CI 10.5-65.7). On logistic regression analysis of multiple risk factors, cooking fuel other than LPG emerged as a significant risk factor for developing ALRTI (adjusted OR 4.73, 95% CI 1.67-13.45) along with poor socio-economic status (adjusted OR 3.38, 95% CI 1.63-7.03). Other than LPG, the main fuels used were wood (95%), kerosene and dung and crop residues. CONCLUSION: Indoor air pollution caused by using cooking fuel other than LPG and socio-economic factors are significantly associated with ALRTI.

Opsismodysplasia.

Opsismodysplasia is a rare osteochondrodysplasia with micromelia and platyspondyly. We report on a neonate with opsismodysplasia. During the antenatal period, polyhydramnios was noted. This is the first report of opsismodysplasia from India. Significant observation was antenatal polyhydramnios.

Trombocitopenia neonatal e hipertensión inducida por el embarazo / Neonatal thrombocytopenia and pregnancy induced hypertension

La trombocitopenia en los neonatos se produce debido a diversas causas y la hipertensión inducida por el embarazo se halla entre las etiologías de origen materno. La frecuencia y la gravedad de la trombocitopenia son variables. La gravedad de la trombocitopenia puede influir sobre la morbilidad, requerir intervención y raramente puede llevar a hemorragias potencialmente mortales. La mejor comprensión de la trombocitopenia debido a su etiología permite optimizar la atención. En esta reseña, el autor analiza la frecuencia, los mecanismos, la gravedad, las características y el curso natural, así como las opciones terapéuticas de la trombocitopenia neonatal debida a los trastornos hipertensivos del embarazo...