Pseudodominance in Friedreich Ataxia-Impact of High Prevalence of Carriers and Intrafamilial Clinical Variation.
Mov Disord Clin Pract
; 10(4): 670-676, 2023 Apr.
Article
em En
| MEDLINE
| ID: mdl-37070055
ABSTRACT
Background:
Friedreich ataxia (FA) is the most common form of autosomal recessive (AR) ataxia. It is a rare disease, but carriers are frequent (1/100). Pseudodominance in FA has seldomly been reported; it may pose additional challenges for diagnosis. Cases A family with two consecutive generations affected by FA is described. The proband and two younger siblings had typical FA, characterized by infantile-onset ataxia, hyporeflexia, Babinski sign, cardiomyopathy, and loss of ambulation in the second decade of life. Another female sibling had delayed-onset (>25 years old), with mild cerebellar and sensitive ataxia since her mid-30s. Their father presented very late-onset FA (>40 years old), with sensitive axonal neuropathy. All five patients had biallelic (GAA)n expansion in FXN. The first three had larger expansions (>800 repeats), while the latter two had one shorter expanded allele (~90 repeats). Literature Review Pseudodominant inheritance has been described in 13 neurological disorders. Seven are movement disorders, of which three were associated with high frequency of carriers (FA, Wilson's disease and PRKN-related parkinsonism).Conclusions:
Clinicians should be aware of the possibility of pseudodominance when facing an apparent autosomal dominant pedigree, particularly in disorders with high frequency of carriers and variable expression. Otherwise, genetic diagnoses may be delayed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prevalence_studies
/
Risk_factors_studies
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article