Clinics
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Hirschsprung disease is a congenital form of aganglionic megacolon that results from cristopathy. Hirschsprung disease usually occurs as a sporadic disease, although it may be associated with several inherited conditions, such as multiple endocrine neoplasia type 2. The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease. ⋯ Presently, there is strong evidence favoring the hypothesis that specific inactivating haplotypes play a key role in the fetal development of congenital megacolon/Hirschsprung disease. In the present study, we report the genetic findings in a novel family with multiple endocrine neoplasia type 2: a specific RET haplotype was documented in patients with Hirschsprung disease associated with medullary thyroid carcinoma, but it was absent in patients with only medullary thyroid carcinoma. Despite the limited number of cases, the present data favor the hypothesis that specific haplotypes not linked to RET germline mutations are the genetic causes of Hirschsprung disease.
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Spinocerebellar ataxias are neurodegenerative disorders involving the cerebellum and its connections. There are more than 30 distinct subtypes, 16 of which are associated with an identified gene. The aim of the current study was to evaluate a large group of patients from 104 Brazilian families with spinocerebellar ataxias. ⋯ Spinocerebellar ataxia 3 was the most common subtype examined, followed by spinocerebellar ataxia 10. Patients with spinocerebellar ataxia 2 and 7 demonstrated highly suggestive features, whereas the phenotype of spinocerebellar ataxia 3 patients was highly pleomorphic and spinocerebellar ataxia 10 patients exhibited pure cerebellar ataxia. Epilepsy was absent in all of the patients with spinocerebellar ataxia 10 in this series.
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Multiple endocrine neoplasia type 2 is an autosomal-dominant hereditary cancer syndrome caused by missense gain-of-function mutations of the rearranged during transfection proto-oncogene, which encodes the receptor tyrosine kinase, on chromosome 10. It has a strong penetrance of medullary thyroid carcinomas and can be associated with bilateral pheochromocytoma and primary hyperparathyroidism. Multiple endocrine neoplasia type 2 is divided into three varieties depending on its clinical features: multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2B, and familial medullary thyroid carcinoma. ⋯ Offering rearranged during transfection testing is the best practice for the clinical management of patients at risk of developing multiple endocrine neoplasia type 2, and multiple endocrine neoplasia type 2 has become a classic model for the integration of molecular medicine into patient care. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on the classification of rearranged during transfection mutations into risk levels according to genotype-phenotype correlations. Earlier identification of patients with hereditary medullary thyroid carcinoma can change the presentation from clinical tumor to preclinical disease, resulting in a high cure rate of affected patients and a much better prognoses.
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The risk of patients with Hirschsprung's disease later developing multiple endocrine neoplasia remains a matter of concern. The multiple endocrine neoplasia 2-Hirschsprung's disease association has been shown to cosegregate in Hirschsprung's disease patients with both short- and long-segment aganglionosis, although patients with long-segment aganglionosis a to carry the greatest risk. The Hirschsprung's disease-medullary thyroid carcinoma relationship also appears to be bi-directional, and activation or suppression of the rearranged during transfection gene appeared to vary over succeeding generations within the same family. ⋯ The clinical awareness of possible medullary thyroid carcinoma has led to timely intervention and early treatment of this chemo- and radioresistant tumor with poor prognosis. Establishment of "risk" by genetic testing has become a classic model of molecular medicine being integrated into patient care and offering rearranged during transfection directed prophylactic surgical management. In addition, novel approaches to treatment based on this genetic knowledge have already shown early promise in randomized clinical trials.
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The aim of this study was to measure dynamic lung hyperinflation and its influence on dyspnea perception in moderate and severe chronic obstructive pulmonary disease patients after performing activities of daily living. ⋯ Chronic obstructive pulmonary disease patients exhibited reductions in inspiratory capacity and increases in dyspnea perception during commonly performed activities of daily living, which may limit physical performance in these patients.