Malaquias Maria João, Oliveira Jorge, Santos Manuela, Brandão Ana Filipa, Sardoeira Ana, Sequeiros Jorge, Barros José, Damásio Joana
Neurology Department Centro Hospitalar Universitário do Porto Porto Portugal.
Unidade de Investigação Genética e Epidemiológica em Doenças Neurológicas (UnIGENe), Institute for Molecular and Cell Biology (IBMC), Instituto de Investigação e Inovação em Saúde (i3S) Universidade do Porto Porto Portugal.
Mov Disord Clin Pract. 2023 Feb 25;10(4):670-676. doi: 10.1002/mdc3.13694. eCollection 2023 Apr.
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.
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) expansion in . The first three had larger expansions (>800 repeats), while the latter two had one shorter expanded allele (~90 repeats).
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 -related parkinsonism).
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.
弗里德赖希共济失调（FA）是常染色体隐性（AR）共济失调最常见的形式。它是一种罕见疾病，但携带者很常见（1/100）。FA中的假显性很少被报道；它可能给诊断带来额外挑战。
描述了一个连续两代受FA影响的家庭。先证者和两个年幼的兄弟姐妹患有典型的FA，其特征为婴儿期发病的共济失调、反射减退、巴宾斯基征、心肌病以及在第二个十年失去行走能力。另一个女性兄弟姐妹发病较晚（>25岁），自35岁左右起患有轻度小脑性和感觉性共济失调。他们的父亲发病非常晚（>40岁），患有感觉性轴索性神经病。所有五名患者在[具体基因名称]中均有双等位基因（GAA）扩增。前三人有更大的扩增（>800次重复），而后两人有一个较短的扩增等位基因（~90次重复）。
在13种神经系统疾病中描述了假显性遗传。其中7种是运动障碍，其中3种与高频率携带者相关（FA、威尔逊病和[具体疾病名称]相关帕金森病）。
临床医生在面对明显的常染色体显性谱系时，应意识到假显性的可能性，尤其是在携带者频率高且表现可变的疾病中。否则，可能会延迟基因诊断。
