Penetrance estimation of TTR familial amyloid polyneuropathy (type I) in Brazilian families.

BACKGROUND AND PURPOSE: Familial amyloid polyneuropathy (FAP) type I is a severe autosomal dominant inherited neuropathy associated with mutations in the transthyretin (TTR) gene. Significant phenotypic variability is seen amongst families with distinct geographic origin, especially regarding penetrance and age of onset. The aim of this study was to estimate the penetrance of FAP in Brazilian families. METHODS: Twenty-two distinct families were ascertained through genetically confirmed index cases and included in this study. Genealogical and clinical data were obtained from a total of 623 individuals, including 126 affected by FAP. In 15 families, TTR genotyping was performed in all available relatives (n = 86), after informed written consent. Seven families did not consent for genetic testing, but agreed to provide clinical and genealogical data. Penetrance was estimated using a previously described method based on survival analysis and corrected for ascertainment bias. RESULTS: Mean age of onset in our sample was 34.5 years, with a significant earlier onset in males (31.1 vs. 35.9, P < 0.0001). The penetrance of FAP in our sample was estimated as 83% (95% CI: 66-99) after 60 years. CONCLUSION: Our results provide new information on FAP in Brazilian patients and may be helpful in the genetic counseling of this population.

Discordant expression of familial amyloid polyneuropathy in monozygotic Brazilian twins.

Discordant expression of Familial Amyloid Neuropathy (FAP) in monozygotic twins is a rare event. Only five such cases have been described in the literature so far. We report the clinical, neurophysiologic and autonomic findings of Brazilian monozygotic twins discordant for the expression of FAP type I. Twin I first presented symptoms at the age of 21, when his brother was completely asymptomatic. Twin 2 only presented symptoms at the age of 25, almost four years after his brother. Both brothers eventually developed the complete phenotype of FAP type I. The occurrence of monozygotic twins discordant for the expression of FAP type I suggests that other factors beside TTR gene mutations should play an important role in the pathogenesis of this condition. Environmental factors, as well as modifier genetic loci are likely to modulate the expression of FAP type I and the study of cases such as the one presented here may help to identify some of these factors.

[Electroneuromyography and somatosensory evoked potentials in HTLV-I associated myelopathy]. / Eletroneuromiografia e potenciais evocados somatossensitivos na mielopatia pelo HTLV-I.

The objective of the present study was to correlate electroneuromyography (ENMG) and evoked potentials findings with clinical aspects and intrathecal synthesis of HTLV-I antibodies production on HTLV-I myelopathy (HAM). Patients were seropositive for HTLV-I by different assays and seronegative for HIV and VDRL. They had no other causes of myelopathy and peripheral neuropathy. Peripheral neuropathy was established in 34.3% of the cases by ENMG. Peripheral neuropathy was mostly asymmetric (82%), sensory motor (90%), axonal (54.5%) or of a mixed type (45.4%). In 63.6% of these cases related symptoms were observed. ABR was abnormal in one patient and the PRVEP in 28.5%, who were symptom-free. The SEP was abnormal in 85.7% of the cases, half of them presenting clinical complaints. In only 14% of the individuals with clinical manifestations, SEP was normal. In 28% of patients with abnormal SEP the ENMG disclosed a peripheral neuropathy.

Electroneuromyography and neuromuscular findings in 16 primary hypothyroidism patients.

There has been few reports on electroneuromyography (ENMG) changes in hypothyroidism. The objectives of the present study were to investigate the frequency of ENMG abnormalities in hypothyroidism and correlate them with neurological signs and symptoms and muscle enzyme levels; and to compare latency, amplitude and nerve conduction velocity from selected nerves with controls. Sixteen patients suffering from primary hypothyroidism were submitted to ENMG before treatment. ENMG abnormalities were found in 87.5% of the patients; 46.6% had myopathy and 43.7% had carpal tunnel syndrome. There was no case of polyneuropathy. A clear-cut clinical, laboratorial and ENMG correlation was observed in patients with myopathy and carpal tunnel syndrome. The patients showed a significant tendency of nerve conduction slowness as compared with controls. The findings are in accordance with the well-known nerve and muscle damage in hypothyroidism.