Dulika S. Sumathipala

Autosomal dominant hereditary ataxia in Sri Lanka

BackgroundSpinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype.MethodsThirty four patients with autosomal dominant ataxia were recruited. For every patient the following was done: recording of clinical details and genotyping for SCA 1, 2, 3, 6, 7, 8, 12, and 17.ResultsSixty one per cent of the subjects were identified as SCA1. One subject had SCA2, 12 remain unidentified. Mean age at onset was 34.8 ± 10years for SCA1 and 32.7 ± 9.8 for non SCA1. 76% of SCA1 patients and 50% of non SCA1 were using walking aids. Quantification of symptoms and signs were similar in the SCA1 and non SCA1 groups. Clinical depression was evidenced in 68.4% of SCA1 and 75% non SCA-1 patients. Mean CAG repeat length in SCA1 patients was 52.0 ± 3.8, with greater anticipation seen with paternal inheritance.ConclusionSCA1 was the predominant subtype and showed similar phenotype to previous reports. However, disease severity was higher and depression more prevalent in this population than previously described.

A Study on Hereditary Thrombophilia and Stroke in a Cohort from Sri Lanka

BACKGROUND Thrombophilia is an enhanced tendency of arterial or venous blood clot formation. The frequently assessed hereditary thrombophilia mutations associated with stroke are methylenetetrahydrofolate reductase (MTHFR) c.677C>T, Factor V (F5) c.1691G>A (Leiden), and prothrombin (F2) c.20210G>A. The aim of this study was to describe the prevalence of the 3 mutations in ischemic stroke patients in Sri Lanka. METHODS A database of clinical details and genetic test results of stroke patients referred for thrombophilia screening from June 2006 to April 2014 was maintained prospectively and analyzed retrospectively. RESULTS A total of 400 ischemic stroke patients (319 arterial, 66 venous, and 15 location unreported) were screened for hereditary thrombophilia. Patients with the MTHFR c.677C>T, F5 c.1691G>A, and F2 c.20210G>A mutations were 17.3%, 3.3%, and .5% of the total cohort, respectively. F5 mutation was present in a statistically significant number of patients with venous thrombosis (P = .005) compared to patients with arterial thrombosis. The MTFHR and F2 mutations showed no such significant association. The mean age of patients with MTHFR, F5, and F2 mutations was 29 (±15), 34 (±11), and 38 (±5.6) years, respectively. CONCLUSION MTHFR c.677C>T is the predominant mutation and the only mutation that had patients with the homozygous mutant genotype. Venous thrombosis showed a significant association with the F5 c.1691G>A mutation.

An infant born to a mother with gestational diabetes presenting with 49,XXXXY syndrome and renal agenesis-a case report.

49,XXXXY is a rare sex chromosome polysomy with an incidence of 1 in 85 000 male births. It has a characteristic triad of mental retardation, skeletal malformation and hypogonadism. This is the first case report of a child with 49,XXXXY syndrome and renal agenesis. This child was referred for genetic testing at 14 years of age due to facial dysmorphism and hypergonadotropic hypogonadism. He had coarse facial features, cryptorchidism of the right testis, genu valgus deformities, and patent ductus arteriosus which are known associations of 49,XXXXY syndrome. He also had agenesis of the right kidney, hydronephrosis of the left kidney with hydroureter which is not a known association of 49,XXXXY syndrome. The patient was the offspring of a mother with gestational diabetes. There is a strong correlation between maternal diabetes and congenital anomalies, especially renal and cardiovascular anomalies. Additionally, it has been noted that gestational diabetes increases the incidence of chromosomal aneuploidies. The teratogenic effects of maternal diabetes during embryogenesis may be the causative factor for the final phenotype of 49,XXXXY syndrome and renal agenesis. Conflict of interest:None declared.

Inherited Neurodegenerative Disorders

Neurodegeneration is the progressive loss of function of neurons and an inescapable event in incurable diseases involving Huntington Disease (HD), Parkinson Disease (PD), and Alzheimer Disease (AD). These and other such diseases share similar pathogenic mechanisms including atypical protein assembly, oxidative pathway dysfunction, and apoptotic cellular death. Neuronal degeneration may be exhibited at different levels like neuronal circuitry aligning from molecular to systemic levels.

The Provision of Medical and Health Genetics and Genomics in the Developing World

The provision of medical and health genetics and genomics in the developing world lags far behind the developed world. In this chapter we laid out the framework for examining the provision of genetics and genomics based on consensus documents, and thereafter identified and highlighted some examples of good practice from the developing world so as to create visibility to those initiatives and to encourage others to take on such initiatives in their own settings. The ultimate goal is to ensure that no one is left behind as the wave of genomic medicine sweeps across the world from West to East.

Analyzing the necessity of prophylactic antibiotic usage in laparoscopy for uncomplicated gynecologic conditions in Sri Lanka

The use of prophylactic antibiotics for laparoscopy of uncomplicated gynecologic conditions is controversial. The aim of this study was to assess whether prophylactic antibiotics is necessary to prevent early postoperative infections and febrile morbidity in elective laparoscopic surgery for benign gynecologic conditions.