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Age‐dependent risks in genetic counseling for spinocerebellar ataxia type 2
Author(s) -
Almaguer Mederos LE,
Proenza CL,
Rodríguez Almira Y,
Escalona Batallán K,
Santos Falcón N,
Martínez Góngora E,
Cuello Almarales D,
Velásquez Pérez L,
Paneque Herrera M
Publication year - 2008
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2008.01073.x
Subject(s) - spinocerebellar ataxia , rehabilitation , ataxia , medicine , pediatrics , physical therapy , psychiatry
To the Editor: Spinocerebellar ataxia type 2 (SCA2, OMIM 183090) belongs to a group of hereditary neurodegenerative diseases caused by the expansion of a CAG repeat tract in coding regions of novel genes. This group includes Huntington’s disease (HD), spinal and bulbar muscular atrophy (SBMA), dentatorubral-pallidoluysian atrophy, and the spinocerebellar ataxias type 1, 3, 6, 7, and 17 (1). These mutations show a very high penetrance, and they follow an autosomal dominant inheritance pattern with the only exception of SBMA (X-linked); each descendant of an affected patient has an a priori risk of 50%. However, it has been proven that the empiric risk of having inherited the mutation causing HD or SCA3 (Machado–Joseph disease) lessens with advancing age (2, 3). This fact has significant implications in the genetic counseling of at-risk individuals. The accuracy and precision that are achieved in the estimate of the risk of developing a certain hereditary illness will have a very important impact in decision making linked to health, reproductive, financial matters, and family planning. Therefore, we undertook a survey of the age of onset in a cohort of SCA2 patients from Holguı́n province, Cuba, to estimate a more objective age-dependent risk, useful for genetic counseling. For the purposes of this investigation, we assembled data from 748 symptomatic SCA2 patients with known age at onset, belonging to 101 unique families studied during a genetic survey carried out on the world’s largest and genetically homogenous SCA2 population in Holguı́n, Cuba. The diagnosis of SCA2 was made on the basis of clinical data, family history or molecular testing by polymerase chain reaction (4). Age at onset was defined as the onset of motor impairment and was based on a combination of information provided by the patient, a close relative or both, related to subjective complains of the diagnostic symptoms of gait ataxia, dysarthria, dysmetria, adiadochokinesia