Genetic factors and therapy outcomes in persistent developmental stuttering.

PURPOSE: We investigated whether outcomes of therapy for persistent developmental stuttering differ in individuals who carry a mutation in one of the known genes associated with stuttering compared to individuals without such mutations. METHOD: We studied outcomes of an intensive fluency shaping-based therapy program in individuals with persistent developmental stuttering. We evaluated a cohort of 51 stuttering individuals with who carried a mutation in either the GNPTAB, GNPTG, NAGPA, or AP4E1 gene. We compared therapy outcomes in these individuals with outcomes in 51 individuals matched for age, gender, and ethnicity, who stutter and underwent the same therapy program, and did not carry a mutation in any of these genes. Fluency pre- and post-therapy was evaluated using blinded observer-based quantitative stuttering dysfluency measures (Dysfluent Words Score, DWS), and by subjects' self-reported measures of struggle, avoidance and expectancy behavior associated with speaking (Perceptions of Stuttering Inventory, PSI). The difference between pre- and post-therapy fluency scores was taken as the measure of near-term therapy efficacy. RESULTS: Comparison of fluency measures showed a strong effect of therapy overall. Mutation carriers achieved significantly less resolution in PSI following therapy, with PSI scores showing significantly less improvement in individuals who carry a mutation (p = 0.0157, RR = 1.75, OR = 2.92) while the group difference in DWS between carriers and non-carriers was statistically not significant in the present study, the trend observed in the results warrants further research focused on this important issue. CONCLUSIONS: These results suggest stuttering is more resistant to therapy in individuals who carry a mutation in one of the genes known to be associated with stuttering.

Mucolipidosis types II and III and non-syndromic stuttering are associated with different variants in the same genes.

Homozygous mutations in GNPTAB and GNPTG are classically associated with mucolipidosis II (ML II) alpha/beta and mucolipidosis III (ML III) alpha/beta/gamma, which are rare lysosomal storage disorders characterized by multiple pathologies. Recently, variants in GNPTAB, GNPTG, and the functionally related NAGPA gene have been associated with non-syndromic persistent stuttering. In a worldwide sample of 1013 unrelated individuals with non-syndromic persistent stuttering we found 164 individuals who carried a rare non-synonymous coding variant in one of these three genes. We compared the frequency of these variants with those in population-matched controls and genomic databases, and their location with those reported in mucolipidosis. Stuttering subjects displayed an excess of non-synonymous coding variants compared to controls and individuals in the 1000 Genomes and Exome Sequencing Project databases. We identified a total of 81 different variants in our stuttering cases. Virtually all of these were missense substitutions, only one of which has been previously reported in mucolipidosis, a disease frequently associated with complete loss-of-function mutations. We hypothesize that rare non-synonymous coding variants in GNPTAB, GNPTG, and NAGPA may account for as much as 16% of persistent stuttering cases, and that variants in GNPTAB and GNPTG are at different sites and may in general, cause less severe effects on protein function than those in ML II alpha/beta and ML III alpha/beta/gamma.

Is preventive medicine a component of the primary care service for diabetes in Barbados? - abstract

Diabetes mellitus is a chronic illness that requires continued medical care and education to prevent acute complications and to reduce the risk of long-term complications. Diabetics should receive care and treatment from a health team with interest and expertise in the management of diabetes. This study aimed to evaluate the quality of care offered to diabetics in three different clinic settings in Barbados. The case notes of 690 diabetic patients attending private practitioner offices, polyclinic general clinics and polyclinic diabetic clinics, were identified during a six-week index period, and a questionnaire was completed for each patient. Although the average number of visits annually was similar in each of the three settings (5-6 visits/year), private practitioners had the lowest percentage of patients (30.7 percent) with poor glycaemic control (defined here as a fasting blood sugar >/=8 mmol/l, or any other blood sugar >/=10 mmol/l. Overall, the glycaemic control was poor in 44.9 percent of patients. Screening for potential long-term complications such as cardiovascular complications, foot problems, eye problems and kidney problems was recorded as being done in a minority of patients, while the concomitant menace of poorly controlled hypertension, which is known to accelerate the progression of diabetic complications, was present in a significant number of patients. While recognising the limitations of the technique of case note review, these results indicate a need for clear concise guidelines for diabetic primary care, with emphasis on prevention and early detection (AU)

Morbidity in general practice in Barbados

From September 1977, 11 general practitioners took part in a survey of 12 months' duration in which they recorded morbidity at every doctor-patient encounter. 35,143 patients made 53,094 encounters and a total of 62,932 problems were identified. The most common reason for going to the doctor was for examination with no disease detected. Acute upper respiratory tract infections, hypertension and pregnancy were the 3 most common specific problems with which the doctors dealt. The results demonstrated some features of general practice such as the abundance of the common diseases, the need to be alert to the infrequent occurrence of wide range major disease, pre-symptomatic screening of the healthy "at risk" patient and the problems of the ill-defined conditions. Comparisons with other surveys show some similarities in general practice morbidity, but also important differences that can be related to prevailing local conditions (AU)