Very mild presentation in adult with classical cellular phenotype of ataxia telangiectasia

Worth, Paul; Srinivasan, Venkataramanan; Smith, Anna Jo Bodurtha; Last, James I.; Wootton, Laura L.; Biggs, Paul; Davies, Nicholas; Carney, Ellen F.; Byrd, Philip J.; Taylor, Alexander M.

doi:10.1002/mds.25236

Cited by 34 publications

(26 citation statements)

References 30 publications

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“…6,10,12,18,21 Our results and the previous literature also demonstrate that movement disorders are not the only gateway to the diagnosis of adult forms of A-T: diagnosis may also be evoked in front of nonspecific clinical signs and ocular motor abnormalities characterized by saccadic pursuit and dysmetric saccades with normal latency and velocity, or in cases of sensorimotor length-dependent axonal neuropathy, frequently with prominent distal motor involvement or even distal spinal muscular atrophy. In addition to cerebellar ataxia, we found subcortical involvement with dystonia and subcortical myoclonus, corticospinal tract signs, frontal involvement in the ocular motor recordings, periventricular white matter changes, and peripheral nerve abnormalities.…”

Section: In Typical Patients With A-t (Ns)supporting

confidence: 69%

“…Brain imaging may also be misleading as 2 patients did not have cerebellar atrophy, and one of them had T2 hyperintense white matter lesions. Immunoglobulin deficiency is relatively rare in mild A-T forms, but has been described before, 10,33 and was present in 2 patients with otherwise mild phenotypes in our series. [25][26][27] The extreme variability of phenotypes of patients with A-T renders diagnosis difficult and laboratory tests may be helpful.…”

Section: In Typical Patients With A-t (Ns)supporting

confidence: 53%

“…11 Association of general clinical features such as telangiectasia, recurrent infections, endocrine abnormalities, and malignancies are evocative when present, but their absence in no way dismisses the diagnosis, especially in adults. 6,[8][9][10]17,[30][31][32][33] This could be explained in part by examination of an insufficient number of mitoses in some of our patients. This is not an isolated finding, as the same type of lesion has been described in rare A-T cases before.…”

Section: In Typical Patients With A-t (Ns)mentioning

confidence: 82%

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The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia

et al. 2014

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Section: In Typical Patients With A-t (Ns)supporting

confidence: 69%

Section: In Typical Patients With A-t (Ns)supporting

confidence: 53%

Section: In Typical Patients With A-t (Ns)mentioning

confidence: 82%

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The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia

et al. 2014

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“…Abnormalities in gonadal development and function appear to be more prominent in females than males [3]. We are aware of pregnancies in people with mild forms of A-T ([77] and unpublished observations), but not in anyone with the classic form of the disease.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, three documented “null” milds have been reported in the literature [77, 106]. The neurological presentation and progression of their disease is mild.…”

Section: Introductionmentioning

confidence: 99%

Ataxia telangiectasia: a review

Rothblum-Oviatt

Wright²,

Lefton‐Greif

et al. 2016

Orphanet J Rare Dis

487

488

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Definition of the diseaseAtaxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome.EpidemiologyThe world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births.Clinical descriptionA-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations.EtiologyA-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress.DiagnosisThe diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels). Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the finding of an absence or deficiency of the ATM protein or its kinase activity in cultured cell lines, and/or identification of the pathological mutations in the ATM gene.Differential diagnosisThere are several other neurologic and rare disorders that physicians must consider when diagnosing A-T and that can be confused with A-T. Differentiation of these various disorders is often possible with clinical features and selected laboratory tests, including gene sequencing.Antenatal diagnosisAntenatal diagnosis can be performed if the pathological ATM mutations in that family have been identified in an affected child. In the absence of identifying mutations, antenatal diagnosis can be made by haplotype analysis if an unambiguous diagnosis of the affected child has been made through clinical and laboratory findings and/or ATM protein analysis.Genetic counselingGenetic counseling can help family members of a patient with A-T understand when genetic testing for A-T is feasible, and how the test results should be interpreted.Management and prognosisTreatment of the neurologic problems associated wit...

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