The Multiple Faces of Spinocerebellar Ataxia type 2

Abstract

Spinocerebellar ataxia type 2 (SCA2) is among the most common forms of autosomal dominant ataxias, accounting for 15% of the total families. Occurrence is higher in specific populations such as the Cuban and Southern Italian. The disease is caused by a CAG expansion in ATXN2 gene, leading to abnormal accumulation of the mutant protein, ataxin‐2, in intracellular inclusions. The clinical picture is mainly dominated by cerebellar ataxia, although a number of other neurological signs have been described, ranging from parkinsonism to motor neuron involvement, making the diagnosis frequently challenging for neurologists, particularly when information about the family history is not available. Although the functions of ataxin‐2 have not been completely elucidated, the protein is involved in mRNA processing and control of translation. Recently, it has also been shown that the size of the CAG repeat in normal alleles represents a risk factor for ALS, suggesting that ataxin‐2 plays a fundamental role in maintenance of neuronal homeostasis.

Spinocerebellar ataxia type 2—neuronopathy or neuropathy?

“…Type 2 autosomal dominant spinocerebellar ataxia (SCA2), caused by a CAG triplet repeat expansion in the ATXN2 gene on the long arm of chromosome 12 (12q23‐24.1), is the second most prevalent of the polyglutamine expansion SCAs worldwide, after SCA3, accounting for 15% of all cases . Clinically, SCA2 is a “cerebellar plus” syndrome in which core cerebellar signs of gait ataxia, dysmetria, dysarthria and action tremor are associated with involvement of other parts of the nervous system.…”

“…Symptoms or signs of peripheral nerve involvement are common. Reduced vibration sense, hyporeflexia, and abnormal peripheral nerve conduction studies are present in most patients with fully manifested disease . Reduced amplitudes of the sensory nerve action potentials have been detected in presymptomatic carriers up to 8 years before the onset of cerebellar signs …”

A clinical report of the massive CAG repeat expansion in spinocerebellar ataxia type 2: Severe onset in a Mexican child and review previous cases

“…SCA2 is the most prevalent of the polyQ ataxias in Cuba, India, Mexico, and Southern Italy, and the second most prevalent worldwide, accounting for 15% of all cases ( Antenora et al , 2017 ). An infantile onset is an uncommon occurrence presentation with only nine reports in the literature and is associated with extremely large CAG expansions (range 100–200 repeats).…”

“…An infantile onset is an uncommon occurrence presentation with only nine reports in the literature and is associated with extremely large CAG expansions (range 100–200 repeats). On the other hand, there are severe infantile cases with expansions between 50-70 repeats, sometimes is related with interruption CTG or CAA as occurs in adults with SCA2 and amyotrophic lateral sclerosis, which also leads to instability of ATXN2 mRNA ( Choudhry et al , 2001 ; Antenora et al , 2017 ), and meiotic instability a general feature of SCA2 without a familial history ( Babovic et al , 1998 ; Mao et al , 2002 ; Moretti et al , 2004 ; Dirik et al , 2007 ; Abdel and Zaki, 2008 ; Paciorkowski et al , 2011 ; Di Fabio et al , 2012 ; Vinther-Jensen et al , 2013 ; Singh et al , 2014 ). However, cases with infantile SCA2 are explain by these features; there are childhood onset cases reported with mosaicism in germ cells such as spermatozoa with larger expanded alleles more than in peripheral blood cells ( Moretti et al , 2004 ; Dirik et al , 2007 ; Abdel and Zaki, 2008 ; Vinther-Jensen et al , 2013 ).…”

Progression of spinocerebellar ataxia type 2. What do we need to know?

“…S pinocerebellar ataxia type 2 (SCA2) is one of the most common autosomal dominant cerebellar ataxias, accounting for 15% of cases within families 1 . It is caused by abnormal CAG expansions in the ATXN2 gene and may affect individuals worldwide.…”