Childhood-Onset Movement Disorders Can Mask a Primary Immunodeficiency: 6 Cases of Classical Ataxia-Telangiectasia and Variant Forms

Abstract

Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder (PID) characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient’s needs. Besides the classical ataxia-telangiectasia (classical A-T) phenotype, a variant phenotype (variant A-T) exists with partly overlapping but some distinctive disease characteristics. Here we present a case series of 6 patients with classical A-T and variant A-T, which illustrates the phenotypic variability of A-T that can present in childhood with prominent extrapyramidal features, with or without cerebellar ataxia. We report the clinical data, together with a detailed genotype description, immunological analyses, and related expression of the ATM protein. We show that the presence of some residual ATM kinase activity leads to the clinical phenotype variant A-T that differs from the classical A-T. Our data illustrate that the diagnosis of the variant form of A-T can be delayed and difficult, while early recognition of the variant form as well as the classical A-T is a prerequisite for providing a correct prognosis and appropriate rehabilitation and support, including the avoidance of diagnostic X-ray procedures, given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment.

Ataxia Telangiectasia Presenting as Cervical Dystonia

“…Patients with a homozygous mutation usually have some form of neurological complaint [1,5]. The atypical A-T has milder clinical features and cerebellar ataxia, oculocutaneous telangiectasia, and oculomotor apraxia are uncommon in atypical A-T [3]. The mutations in atypical A-T segregate within families, and the affected members of the family as a whole may present with movement problems rather than ataxia as the major hallmark of the condition.…”

“…It is characterized by respiratory complaints such as bronchitis, bronchiectasis, and sinusitis; neurological complaints such as poor muscle coordination (clumsiness); and movement disorders such as dystonia, choreoathetosis, myoclonus, and tremors [1]. General physical appearance is characterized by the presence of short stature, café au lait spots, progeric skin and hair changes, oculocutaneous telangiectasia, horizontal head thrusts due to difficulty in initiating horizontal saccades (both voluntary and reflex saccades are affected), ocular apraxia, diabetes mellitus, and features of glucose intolerance like acanthosis nigricans, hypogonadism, lymphocytopenias, predisposition to malignancy, hypoimmunoglobulinemia, and other immune defects [2][3].…”

Cervical dystonia and no oculomotor apraxia as new manifestation of ataxia-telangiectasia-like disorder 1 – case report and review of the literature

“…Patients also suffer from immunodeficiency, radiosensitivity, cancer susceptibility, recurrent sinopulmonary infections and high levels of serum alfa-fetoprotein. AT phenotypes vary, from severe early-onset to milder adult-onset, depending on the type of mutation ( 14 , 15 ).…”