Methyl-CpG-binding protein 2 gene mutations and its association with epilepsy: a single centre study from the Indian subcontinent

Rett syndrome (RTT) is an X-linked disorder caused by mutations in MECP2 in majority of cases. It is characterized by arrested development between 6 and 18 months of age, regression of acquired hand skills and speech, stereotypic hand movements, gait abnormalities and seizures. There are a very few studies in India which illustrates mutation spectrum in RTT. None of the studies have correlated seizures with the genotype. This study describes the phenotype and genotype spectrum in children with RTT syndrome and analyses the association of epilepsy with various clinical features and molecular findings. All children with RTT in our cohort had global developmental delay. Genetic diagnosis identified mutations of the MECP2 in all 25 children where RTT was suspected. We have identified point mutations in 20 patients, one insertion and four deletions by Sanger sequencing, namely c.1164_1207 (44 bp), c.1165_1207 (43 bp), c.1157_1197 (41 bp) del and c.1157_1188 (32 bp). Clinically, none of the patients with deletion had seizures. We identified one novel insertion variant c.337_338 (p.S113Ffs*9). All the deletions were located in the C-terminal region. Majority of the mutations (22/25) were identified in exon 4 which comprised of nonsense and missense types. Screening of hotspot mutations in exon 4 should be the first line evaluation in diagnosis of RTT. Molecular testing could help in specific management of seizures in RTT.

Effects of Elevated Blood Lead Levels in Preschool Children in Urban Vellore.

Objectives: To study the burden and associated risk factors for elevated blood lead levels among pre-school children (15-24 months) in urban Vellore, and to study its effects on child cognition and anemia. Design: An investigative study through Mal-ED cohort. Setting: Eight adjacent urban slums in Vellore, Tamil Nadu. Participants: 251 babies recruited through Mal-ED Network. Outcome measures: Blood lead levels using Graphite Furnace Atomic Absorption Spectrophotometry method at 15 and 24 mo; hemoglobin estimation by azidemethemoglobin method; cognitive levels using Bayley Scales of Infant Development III. Results: Around 45% of children at 15 months and 46.4% at 24 months had elevated blood lead levels (>10 μg/dL). Among children who had elevated blood lead levels at 15 months, 69.2% (45/65) continued to have elevated levels at 24 months. After adjusting for potential confounders, children from houses having a piped drinking water supply and houses with mud or clay floors were at significantly higher risk of having elevated blood lead levels at 15 months. Thirty one percent (21/67) of the children with elevated blood lead levels had poor cognitive scores. Children with elevated blood lead levels at 15 months had higher risk (Adjusted OR 1.80; 95% CI 0.80 - 3.99) of having poorer cognitive scores at 24 months. More than half of the children (57%) were anemic at 15 months of age, and elevated blood lead levels were not significantly associated with anemia. Conclusions: Elevated blood lead levels are common among preschool children living in urban slums of Vellore. Poorer conditions of the living environment are associated with elevated lead levels.

Mosaic double aneuploidy: Down syndrome and XYY.

Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5‑year‑old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.

Cri du chat syndrome: A series of five cases.

The cri du chat syndrome (CdCS) is a chromosomal deletion syndrome associated with a partial deletion of the short (p) arm of chromosome 5. We describe five children who were diagnosed to have CdCS by conventional cytogenetic analysis. The deletion was at 5p15 in four patients, whereas the fifth had a larger, more proximal deletion at 5p14. Fluorescence in situ hybridization (FISH) analysis confirmed the deletion of the CdCS critical region at 5p15.2. All five children had global developmental delay and dysmorphism with microcephaly. The other clinical features were variable. Since the clinical diagnosis of CdCS may not always be evident because of the phenotypic heterogeneity, cytogenetic analysis is necessary to establish the diagnosis and confirm that the deletion involves the CdCS critical region. This will enable early intervention which plays an important role in improving the outcome.

Growth and Development Profile of Indian Children with Down Syndrome.

In this retrospective study, we describe the profile of 88 children with Down syndrome. The average BMI for children showed a progressive increase with age. Compared to the previously published development profile, there was a significant improvement in the language domain.

Neurodevelopmental Outcome Following Whole Body Cooling for Perinatal Asphyxia.

This follow-up study conducted on children who underwent therapeutic cooling for hypoxic ischemic encephalopathy, showed normal neurodevelopmental outcome with normal milestones and normal developmental quotient in a minimum of 60% of children at 18-24 months of age. This study shows comparable neurodevelopmental outcome in infants who underwent cooling in a resource poor setting, when compared with existing literature.