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.

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.

Pulmonary distress following attempted suicidal hanging.

OBJECTIVE : To assess the incidence of post-hanging pulmonary distress in cases of attempted suicidal hanging and predictors of outcome among these patients. DESIGN : Five-year retrospective analysis. SETTING: Tertiary care center in south India. PATIENTS :A total of 335 patients who attempted suicidal hanging, aged above 16 years, were admitted during this period. Thirty-eight of them with pulmonary distress established clinically and with radiological evidence of pulmonary injury post hanging met the inclusion criteria. MEASUREMENTS : Data from ICU records of 5 years, X-rays and laboratory investigations were reviewed. In patients identified to have post-hanging pulmonary distress, the neurological status, chest x-rays, arterial blood gas values and outcome data were collected and analyzed. RESULTS : Eleven percent (n = 38) of the 335 patients admitted following attempted suicidal hanging were diagnosed to have post-hanging pulmonary distress. The overall mortality among post-hanging patients was 5%, which increased to 34.2% (n = 13) in the presence of pulmonary distress (P < or = 0.001). Among the prognostic factors evaluated, a PaO 2 / FiO 2 (P/F) ratio of < 100 at admission predicted a poor outcome (P < or = 0.001). CONCLUSION : Post-hanging pulmonary distress is a relatively common complication of hanging and is associated with increased mortality. P/F ratio from arterial blood gas at admission was the only significant predictor of outcome in this group of patients.

Role of surgery in pediatric epilepsy.

Twenty five percent of patients with intractable epilepsy have surgically remediable epilepsy syndromes. This article reviews the treatment paradigm for pediatric epilepsy and also the indications, methods, and surgical options for the subgroup of patients with surgically remediable epileptic disorders based on our experience in the management of these children. The article also discusses the rationale for offering surgery and the timing of surgery in these patients. The study of surgically remediable epilepsy can best be divided into focal, sub hemispheric, hemispheric and multifocal epileptic syndromes. These syndromes have both acquired and congenital etiologies and can be treated by resective or disconnective surgery. The surgical management of these conditions (with the exception of multifocal epilepsy) provides Engel's Class 1 outcome(complete seizure freedom) in approximately 80% of children. The consequences of seizure freedom leads to a marked improvement in the quality of life of these children.The benefits to society, of allowing a child to grow to adulthood with normal cognition to earn a livelihood and contribute actively to society, cannot be understated.