Beyond Typical Ataxia Telangiectasia: How to Identify the Ataxia Telangiectasia‐Like Disorders

Raslan, Ivana Rocha; Matos, Paula Camila Alves de Assis Pereira; Ciarlariello, Vinícius Boaratti; Daghastanli, Karyme Hussein; Rosa, Augusto Bragança Reis; Arita, Juliana Harumi; Aranda, Carolina Sánchez; Barsottini, Orlando Graziani Póvoas; Pedroso, José Luiz

doi:10.1002/mdc3.13110

Cited by 12 publications

(12 citation statements)

References 40 publications

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“…Ataxia telangiectasia diagnosis was confirmed by presence of ataxia and raised alfa fetoprotein. Absence of telangiectasia did not rule out the diagnosis (11).…”

Section: Methodsmentioning

confidence: 88%

Ataxia Telangiectasia: A Single Center Experience in a Decade

Mansour

Kotb

Sobkyb

et al. 2022

Pediatric Sciences Journal

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Background: Ataxia Telangiectasia (A-T) is a rare neurodegenerative disorder that affects a number of different systems of the body. Aim of the work:To identify the spectrum of clinical presentations of children with A-T. Methods: Retrospective cohort study of data of 35 children with confirmed diagnosis of A-T. Results: A-T clinical spectrum was diverse with two distinct presentations according to age of onset of symptoms; classic early onset among 29 (82%) (mean age± SD= 2.9 ± 0.63 years) and variant late in 6 (17%) (mean age± SD=9.83 ± 1.34 years). In early onset A-T the leading presentations were classic; ataxia in 100%, telangiectasis (100%), dysarthria (62%), cerebellar atrophy (58%), repeated sinopulmonary infections (48%), autoimmune vitiligo in one child, but not peripheral neuropathy or postural scoliosis. While among those with late onset A-T, the leading presentations were extrapyramidal manifestations and dystonia in (66.6%), late development of ataxia (100%), telangiectasis (50%), dysarthria (66.6%), repeated sinopulmonary infections (16.6%), cerebellar atrophy (16.6%) and peripheral neuropathy (50%). All 35 (100%) had elevated alfa fetoprotein, 74% had reduced IgE levels and 68% had reduced IgA levels. Acute lymphoblastic leukemia (ALL) complicated the course of 17.2% and 16.6% of early and variant late onset A-T respectively, and preceded the onset of ataxia among 50% of affected cases. Conclusion: Ataxia telangiectasia is a rare neurologic disease with various clinical presentations. A-T clinical spectrum is diverse with two distinct presentations according to age of presentation: classic early onset and variant late onset. Immune dysregulation is more pronounced among the early onset group. ALL might be the initial presentation of A-T that precedes the onset of ataxia and of telangiectasis.

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“…Ataxia telangiectasia diagnosis was confirmed by presence of ataxia and raised alfa fetoprotein. Absence of telangiectasia did not rule out the diagnosis (11).…”

Section: Methodsmentioning

confidence: 88%

Ataxia Telangiectasia: A Single Center Experience in a Decade

Mansour

Kotb

Sobkyb

et al. 2022

Pediatric Sciences Journal

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“…The clinical presentation of ATLD overlaps with AT and NBS (radiosensitivity and chromosomal instability), ATLD and AT show neurodegeneration, whereas NBS is characterized by microcephaly [ 86 ]. Compared with AT, symptoms of ATLD have a later onset, slower progression and milder phenotypes [ 87 ]. However, individual cases of ATLD may develop different phenotypes [ 88 ].…”

Section: Germline Alterations Of Mrn Complex Genes In Autosomal Reces...mentioning

confidence: 99%

“…Therefore, the contribution of ATLD to cancer predisposition remains unknown. An X-ray exposure and radiotherapy should be avoided in patients with ATLD [ 87 ].…”

Section: Germline Alterations Of Mrn Complex Genes In Autosomal Reces...mentioning

confidence: 99%

Importance of Germline and Somatic Alterations in Human MRE11, RAD50, and NBN Genes Coding for MRN Complex

Stastna

Volková

Soukupová

et al. 2023

IJMS

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The MRE11, RAD50, and NBN genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. Heterozygous germline alterations in the MRN complex genes have been associated with a poorly-specified predisposition to various cancer types. Somatic alterations in the MRN complex genes may represent valuable predictive and prognostic biomarkers in cancer patients. MRN complex genes have been targeted in several next-generation sequencing panels for cancer and neurological disorders, but interpretation of the identified alterations is challenging due to the complexity of MRN complex function in the DNA damage response. In this review, we outline the structural characteristics of the MRE11, RAD50 and NBN proteins, the assembly and functions of the MRN complex from the perspective of clinical interpretation of germline and somatic alterations in the MRE11, RAD50 and NBN genes.

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“…At age 14 she also developed a focal limb dystonia when writing 61 . MRE11A also participates in telomere length maintenance and DNA double‐strand break repair 62 …”

Section: Movement Disorders With Hypogonadismmentioning

confidence: 99%

“…61 MRE11A also participates in telomere length maintenance and DNA double-strand break repair. 62 Heterozygous sequestome 1 (SQSTM1) gene variants have been recently associated with a progressive childhood-onset neurodegenerative disorder characterized by cognitive decline, ataxia, dystonia, and gaze palsy. Hypergonadotropic hypogonadism has been described in two cases.…”

Section: Ataxia Associated With Other Movement Disorders and Hypogona...mentioning

confidence: 99%

Movement Disorders Associated with Hypogonadism

Gonzàlez‐Latapi

Sousa

Lang

2021

Movement Disord Clin Pract

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A variety of movement disorders can be associated with hypogonadism. Identification of this association may aid in guiding workup and reaching an accurate diagnosis. We conducted a comprehensive and structured search to identify the most common movement disorders associated with hypogonadism. Only Case Reports and Case Series articles were included. Ataxia was the most common movement disorder associated with hypogonadism, including entities such as Gordon‐Holmes syndrome, Boucher‐Neuhäuser, Marinesco‐Sjögren and Perrault syndrome. Tremor was also commonly described, particularly with aneuploidies such as Klinefelter syndrome and Jacob's syndrome. Other rare conditions including mitochondrial disorders and Woodhouse‐Sakati syndrome are associated with dystonia and parkinsonism and either hypo or hypergonadotropic hypogonadism. We also highlight those entities where a combination of movement disorders is present. Hypogonadism may be more commonly associated with movement disorders than previously appreciated. It is important for the clinician to be aware of this association, as well as accompanying symptoms in order to reach a precise diagnosis.

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Beyond Typical Ataxia Telangiectasia: How to Identify the Ataxia Telangiectasia‐Like Disorders

Cited by 12 publications

References 40 publications

Ataxia Telangiectasia: A Single Center Experience in a Decade

Ataxia Telangiectasia: A Single Center Experience in a Decade

Importance of Germline and Somatic Alterations in Human MRE11, RAD50, and NBN Genes Coding for MRN Complex

Movement Disorders Associated with Hypogonadism

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