**1. Introduction**

The first description of patients with ataxia telangiectasia (AT) was published in 1926 [1], but it was not until 1958 that the term "ataxia telangiectasia" was first coined. AT was given its commonly used name by Elena Boder and Robert P. Sedgwick, who described a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia, and frequent pulmonary infection [2]. Ataxia telangiectasia, or AT, is also referred to as the Louis-Bar syndrome (OMIM #208900). Orphanet Orpha Number: ORPHA100.

Ataxia telangiectasia is an autosomal recessive cerebellar ataxia [3]. It is also included in inborn errors of immunity (IEI) with chromosomal instability, DNA repair disorders, and less commonly known as neurocutaneous syndrome [4]. The disease is caused by a mutation in the *ataxia telangiectasia mutated* (*ATM*) gene encoding the serine-threonine protein kinase [5, 6]. ATM is a large protein

(~350 kDa) with a critical role in DNA double-strand break (DSB) repair, genome stability, cell cycle regulation, and cell survival [7]. The ATM protein is involved in natural physiological processes during DNA replication, meiosis, mitosis, V (variable), D (diversity), or J (joining) recombination or immunoglobulin class switching (CSR, class switch recombination). In addition, other targets of the ATM protein are those involved in oxidative stress metabolism [8]. ATM is mainly a nuclear protein, but it is also found in the cytoplasm and regulates the function of mitochondria and peroxisomes, and through this it affects angiogenesis and glucose metabolism. Lack of ATM protein function is associated with the development of certain disorders in AT patients, such as progressive neurodegeneration, immune deficiencies, pulmonary, metabolic, dermatological, and vascular complications [9–11].

Ataxia telangiectasia is characterized by progressive cerebellar degeneration, oculocutaneous telangiectasias, immunodeficiency, recurrent sinopulmonary infections, radiation sensitivity, premature aging, and susceptibility to cancer development, especially of lymphoid origin. Other abnormalities, such as growth failure, poor pubertal development, gonadal atrophy, insulin-resistant diabetes, lung diseases, cutaneous abnormality, and cardiovascular disease, have also been reported in AT patients [12–14].

The prevalence of AT is estimated to be <1–9/100,000. However, the incidence of AT may be higher 1/40,000 in consanguineous population or those populations with founder effect [15]. AT patients have poor prognosis; the median survival is 25 years with a wide range. The two most common causes of death in these patients are chronic pulmonary diseases and malignancy [14, 16]. AT patients show remarkable clinical and laboratory differences that reflect the presence of genotype/phenotype correlations in these patients or other genetic/environmental disease-modifying factors. The majority of ATM mutations lead to a truncated protein, while some missense and splicing site variations cause milder phenotype [17].

Ataxia telangiectasia patients have much milder clinical progress as a result of retained expression of either normal [18, 19] or mutant ATM protein with residual activity [20–22]. These patients often retain the ability to walk into adulthood and consequently might be diagnosed when adults [19, 23]. The terms "classic" and "mild" are used to distinguish two different but widely recognized clinical presentations of AT. People with mild AT have less severe, later onset of symptoms associated with longer survival. Ataxia telangiectasia-like disorder (ATLD) [24–26], ataxia oculomotor apraxia type 1 (AOA1) [27, 28], and ataxia oculomotor apraxia type 2 (AOA2) [29–32] have neurological features similar to those of AT.
