Juvenile Huntington's disease confirmed by genetic examination in twins

Abstract

-Early-onset Huntington's disease (HD) occurs in approximately 10% of HD's cases. We report juvenile HD in phenotypically identical twins, evaluated by history, clinical and neurologic examination, minimental state examination, blood laboratory exams, cerebrospinal fluid examination, skull computed tomography, and genetic examination for HD. Patients had the akinetic-rigid variety (Westphal variant) of the disease and paternal inheritance. The laboratory workup confirmed the clinical diagnosis of HD, which adds this report to the rare cases of HD in twins reported in the literature.KEY WORDS: Huntington's disease, juvenile, twins. Doença de Huntington juvenil confirmada por exame genético em gêmeasRESUMO -Doença de Huntington (DH) de início precoce ocorre em aproximadamente 10% dos casos de DH. Relatamos DH juvenil em gêmeas fenotipicamente idênticas, avaliadas por história, exames clínico e neurológico, mini-exame do estado mental, exames de sangue, exame do líquido cefalorraquidiano, tomografia computadorizada de crânio e exame genético para DH. As pacientes apresentavam a variedade rígido-acinética (variante de Westphal) da doença e herança paterna. A avaliação laboratorial confirmou o diagnóstico clínico de DH, acrescentando-se este relato aos raros casos de DH em gêmeos relatados na literatura.

Two Monozygotic Twin Pairs Discordant for Female-to-Male Transsexualism

“…MZ twin concordance for rare conditions, such as progeria (Henig, 2005) and juvenile Huntington's disease (Levy, Nobre, Cimini, Raskin, & Engelhardt, 1999), supports genetic explanations of these conditions. However, most complex psychological and medical conditions show incomplete MZ twin resemblance.…”

What monozygotic twins discordant for phenotype illustrate about mechanisms influencing genetic forms of neurodegeneration

“…In older case reports, motor symptoms and onset of behavioral symptoms were discordant (15, 16, 23). More recent case reports have shown discordance in motor symptoms, behavioral changes and cognitive differences (14, 18–20). MZ twins significantly differing for HD AO (>6 years) have also been described (17, 22) (Table 1).…”

“…In addition, the existence of MZ twins that are discordant for highly penetrant disorders also reveals that other factors than the causative gene could play a role. Although rare, examples of discordant MZ twins have been described for autosomal dominant neurodegenerative disorders, including HD (14–23) and SCAs (24). In contrast to non‐familial forms of AD, twin discordance for familial AD is also considered as rare, and few cases have been described (4).…”

“…MZ twins that are discordant for HD phenotype, although rare, have been described (14–23) and may be useful to determine crucial modifiers in the development of HD. Despite being genetically (almost) identical, some MZ twins have been reported to extensively differ in the nature of HD symptoms, or show a significant difference in AO.…”

“…Overall, such discordant cases could form an excellent resource to discover crucial factors that determine the phenotypic expression of disease, in addition to the main disease gene, thereby possibly increasing our understanding of phenomena such as reduced penetrance or high AO variability in the disease. A note of caution, however, is the expected low sample size because of the rare occurrence of discordance, especially in case of HD and SCAs (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), or because of difficulties in documentation of discordance. The latter is especially relevant for cases of late onset where one co-twin could have passed away for other reasons than due to the disease (4, 5).…”