A Proposed Clinical Classification and a Diagnostic Approach for Congenital Ataxias.

PURPOSE OF REVIEW: This review proposes a clinical classification for congenital ataxias based on clinical features, neuroimaging, and course of the disease. RECENT FINDINGS: Congenital ataxias are an unusual group of neurologic disorders, with heterogeneous clinical and genetic presentation. Typical clinical features of congenital ataxias include variable degrees of motor developmental delay, very early onset cerebellar ataxia, cognitive impairment, and hypotonia, frequently mistakenly diagnosed as cerebral palsy. Congenital ataxias are usually nonprogressive. Neuroimaging plays an important role in the characterization of congenital ataxias. Despite the development of genetics with exome sequencing, several congenital ataxias remain undetermined, and medical literature on this topic is scarce. SUMMARY: A didactic classification based on the clinical and neuroimaging features for congenital ataxias include the following 4 main groups: cerebellar malformation, syndromic congenital ataxias, congenital cerebellar hypoplasia, and pontocerebellar hypoplasia. A diagnostic approach for congenital ataxias is proposed, and its differential diagnosis is also discussed.

Beyond Typical Ataxia Telangiectasia: How to Identify the Ataxia Telangiectasia-Like Disorders.

BACKGROUND: Ataxia telangiectasia is one of the most common causes of autosomal recessive cerebellar ataxias. However, absence of telangiectasia, normal levels of alpha-fetoprotein and negative genetic test may direct to alternative diagnosis with similar phenotypes such as ataxia telangiectasia-like disorders (ATLD). CASES: We report two instructive cases of ATLD: the first case with ataxia telangiectasia-like disorder type 1 related to MRE11A gene, and the second case with ataxia telangiectasia-like disorder type 2 related to PCNA gene. LITERATURE REVIEW: ATLD is an unusual group of autosomal recessive diseases that share some clinical features and pathophysiological mechanisms with ataxia telangiectasia (AT). ATLD may be associated with mutations in the MRE11A (ATLD type 1) and PCNA (ATLD type 2) genes. ATLD belongs to the group of chromosomal instability syndromes. The reason for the term ATLD is related to the similar pathophysiological mechanisms observed in AT, which is characterized by chromosomal instability and radiosensitivity. CONCLUSIONS: In this review, the main clinical features, biomarkers, brain imaging and genetics of ATLD are discussed. Mutations in the MRE11A and PCNA genes should be included in the differential diagnosis for early onset cerebellar ataxia with absence of telangiectasia and normal levels of alpha-fetoprotein.