Ataxia Telangiectasia Presenting Research Articles

Late-Onset Ataxia-Telangiectasia Presenting With Dystonia and Tremor

Late-Onset Ataxia-Telangiectasia Presenting With Dystonia and Tremor

Clinical and immunological presentation of ataxia-telangiectasia

Clinical and immunological presentation of ataxia-telangiectasia

Clinical characteristics of ataxia-telangiectasia presenting dystonia as a main manifestation

IntroductionBesides cerebellar ataxia, various other movement disorders, including dystonia, could manifest as main clinical symptoms in ataxia-telangiectasia (A–T). However, the clinical characteristics of dystonic A–T patients are not clearly elucidated. MethodsTo investigate the characteristics of dystonic A–T, we screened previous reports with A–T patients presenting dystonia as a main manifestation, and included 38 dystonic A–T patients from 16 previous studies and our 2 cases. We reviewed clinical and demographic data of dystonic A–T patients. Additionally, to figure out clinical meaning of cerebellar involvement in dystonic A–T, we divided them into two groups based on the presence of cerebellar involvement, and compared clinical features between two groups. ResultsIn the patients with dystonic A–T, dystonia tended to appear during childhood or adolescence and became generalized over time. Choreoathetosis and myoclonus accompanied more frequently than the typical clinical features, including cerebellar ataxia or atrophy, telangiectasia, or oculomotor apraxia. Additionally, alpha-fetoprotein level was also elevated in the patients with dystonic A–T. When we compared dystonic A–T with and without cerebellar involvement, the former was related with more chance for telangiectasia and oculomotor apraxia, while the latter with that for choreoathetosis and malignancy. ConclusionEven without ataxia, telangiectasia, or oculomotor apraxia, A–T should be considered in undiagnosed dystonia, especially generalized dystonia which started from childhood or adolescence period, and alpha-fetoprotein level can be a useful screening tool. In addition, cerebellar involvement is important considering different phenotype in dystonic A–T patients with and without cerebellar sign.

An atypical presentation of ataxia telangiectasia in a school-aged boy secondary to an intronic mutation

Background: Ataxia telangiectasia typically presents in early pre-school years with progressive cerebellar ataxia and oculocutaneous telangiectasias. Referral to Immunology is often made after diagnosis has been established, as patients are prone to both humoral and cellular immune abnormalities. Case presentation: We herein report a 10-year old boy, previously undiagnosed, who presented with recurrent pneumonias. On history, frequent falls and speech difficulty were reported, with no telangiectasias on exam. Screening with alpha-fetoprotein was abnormal, followed by ATM gene sequencing, showing a homozygous intronic mutation. Over the next 3 years the patient deteriorated neurologically, and developed appreciable telangiectasias. Conclusion: A review of the literature demonstrates that intronic/splicing mutations may result in atypical ataxia telangiectasia phenotypes and delayed presentations. We advise immunologists to have a high index of suspicion for ataxia telangiectasia when assessing a patient with immunodeficiency and neurologic regression, regardless of age, and even in the absence of telangiectasias. Statement of novelty: We present a case of phenotypically atypical (“leaky”) ataxia telangiectasia resulting from a novel homozygous splice-site mutation in the ATM gene. Given high reported prevalence of intronic and splice-site mutations in ATM, we recommend full gene sequencing in patients suspected to have ataxia telangiectasia, especially in those with late onset or unusual manifestations.

Ataxia Telangiectasia Presenting with Idiopathic Thrombocytopenic Purpura in a 4-Year-Old Boy

Ataxia Telangiectasia (AT) is autosomal recessive disorder, characterized by progressive neuro degeneration telangiectasia, immunodeficiency, cancer susceptibility, and some laboratory abnormalities. It is a rare immunodeficiency disease and AT disease is due to the mutation in the gene Ataxia-Telangiectasia Mutated located on chromosome. This study shows that finally the importance of the clinical case introduced is whether the mutation in gene expressing Ataxia-Telangiectasia Mutated can disrupt the complex mechanisms of central and peripheral tolerance of immune system.

Ataxia Telangiectasia Presenting with Hypogammaglobulinemia and High IgM Levels, Cutaneous Granulomas, and Expansion of CD21(lo) T-bet(+) B Cells

Ataxia Telangiectasia Presenting with Hypogammaglobulinemia and High IgM Levels, Cutaneous Granulomas, and Expansion of CD21(lo) T-bet(+) B Cells

Ataxia telangiectasia presenting as hyper IgM syndrome without neurologic signs

Ataxia telangiectasia presenting as hyper IgM syndrome without neurologic signs

Ataxia Telangiectasia Presenting with Absent IgG, IgA, and Elevated IgM

Ataxia Telangiectasia Presenting with Absent IgG, IgA, and Elevated IgM

Atypical juvenile presentation of Ataxia Telangiectasia: A case report

Atypical juvenile presentation of Ataxia Telangiectasia: A case report

Ataxia telangiectasia presenting as dopa-responsive cervical dystonia

To identify the cause of cervical dopa-responsive dystonia (DRD) in a Muslim Indian family inherited in an apparently autosomal recessive fashion, as previously described in this journal. Previous testing for mutations in the genes known to cause DRD (GCH1, TH, and SPR) had been negative. Whole exome sequencing was performed on all 3 affected individuals for whom DNA was available to identify potentially pathogenic shared variants. Genotyping data obtained for all 3 affected individuals using the OmniExpress single nucleotide polymorphism chip (Illumina, San Diego, CA) were used to perform linkage analysis, autozygosity mapping, and copy number variation analysis. Sanger sequencing was used to confirm all variants. After filtering of the variants, exome sequencing revealed 2 genes harboring potentially pathogenic compound heterozygous variants (ATM and LRRC16A). Of these, the variants in ATM segregated perfectly with the cervical DRD. Both mutations detected in ATM have been shown to be pathogenic, and α-fetoprotein, a marker of ataxia telangiectasia, was increased in all affected individuals. Biallelic mutations in ATM can cause DRD, and mutations in this gene should be considered in the differential diagnosis of unexplained DRD, particularly if the dystonia is cervical and if there is a recessive family history. ATM has previously been reported to cause isolated cervical dystonia, but never, to our knowledge, DRD. Individuals with dystonia related to ataxia telangiectasia may benefit from a trial of levodopa.

Ataxia-Telangiectasia Presenting With a Novel Immunodeficiency

Ataxia-telangiectasia is a rare autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, and variable degrees of immunodeficiency. Immunologic evaluations of affected patients often reveal anomalies of humoral and cell-mediated immunity. We describe a case of ataxia-telangiectasia with an atypical immunodeficiency and a novel mutation in the ATM gene. The patient presented at age 3 years with a perineal cellulitis associated with profound neutropenia and T-cell lymphopenia. Serum immunoglobulin levels and antibody titers were normal. Neurologic evaluation revealed minimal hypotonia and wide-based gait, without other signs of cerebellar dysfunction. The alpha-fetoprotein level was elevated, and molecular genetic testing confirmed the diagnosis of ataxia-telangiectasia, uncovering a novel ATM gene mutation c.3931C>T (p.Gln1311X) in exon 28. This patient presents a unique immunologic pattern with normal immunoglobulin levels, significant lymphopenia, and profound neutropenia. The diagnosis of ataxia-telangiectasia should be considered in children presenting with gait disorder and immunologic defects, regardless of subtype and severity.

Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites

Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites

Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites

To compare the phenotype of primary-appearing dystonia due to variant ataxia-telangiectasia (A-T) with that of other dystonia ascertained for genetics research. Movement disorder specialists examined 20 Canadian Mennonite adult probands with primary-appearing dystonia, as well as relatives in 4 families with parent-child transmission of dystonia. We screened for the exon 43 c.6200 C>A (p. A2067D) ATM mutation and mutations in DYT1 and DYT6. Clinical features of the individuals with dystonia who were harboring ATM mutations were compared with those of individuals without mutations. Genetic analysis revealed a homozygous founder mutation in ATM in 13 members from 3 of the families, and no one harbored DYT6 or DYT1 mutations. Dystonia in ATM families mimicked other forms of early-onset primary torsion dystonia, especially DYT6, with prominent cervical, cranial, and brachial involvement. Mean age at onset was markedly younger in the patients with variant A-T (n = 12) than in patients with other dystonia (n = 23), (12 years vs 40 years, p < 0.05). The patients with A-T were remarkable for the absence of notable cerebellar atrophy on MRI, lack of frank ataxia on examination, and absence of ocular telangiectasias at original presentation, as well as the presence of prominent myoclonus-dystonia in 2 patients. Many also developed malignancies. Ataxia and telangiectasias may not be prominent features of patients with variant A-T treated for dystonia in adulthood, and variant A-T may mimic primary torsion dystonia and myoclonus-dystonia.

Attenuated presentation of ataxia-telangiectasia with familial cancer history

JO N 2857 ing, generalized choreo-athetoid movements, spasmodic torticollis, writing tremor and myoclonic jerks. Examination also revealed cerebellar ataxia. The IQ was liminal. Neuroleptics, DL-hydroxytryptophan, trihexyphenidyl, and piribedil provided little or no improvement. By the age of 42, the patient was confined to a wheelchair, mainly due to the midline cerebellar disturbances. There was also limb ataxia, dystonia of the legs, torticollis and rest tremor. An ocular apraxia was noted without telangiectasia. Cognitive impairment had appeared with executive, judgement, reasoning and fixation memory troubles. Since age 16 a slowly worsening, predominantly sensory axonal neuropathy was known, whereas cerebral imaging showed global cerebellar atrophy. Standard blood tests, copper balance, vitamin E assay were normal. There was no evidence of metabolic or mitochondrial disorders. Genetic analysis excluded Friedreich’s disease, most frequent spinocerebellar ataxias, dentatorubropallidoluysian atrophy and Huntington’s disease. Igs serum level was normal. There was a slight rise in the serum level of αfetoprotein (AFP) (25.1 μg/L, Clemence Simonin David Devos Isabelle Vuillaume Berengere de Martinville Bernard Sablonniere Alain Destee Dominique Stoppa-Lyonnet Luc Defebvre

Different Clinical and Immunological Presentation of Ataxia-Telangiectasia within the Same Family

Ataxia-telangiectasia is a rare multisystem neurodegenerative genetic disorder due to mutation of ATM gene. The clinical expression and the immunological abnormalities are variable and apparently not associated with the type of ATM mutations. We report on two siblings affected by A-T with different clinical and immunological presentations; in particular in one the immunological phenotype was reminiscent of hyper IgM syndrome.

844 Atypical presentation of ataxia-telangiectasia (AT) with features of non-X-linked hyperIgM (HIGM)

844 Atypical presentation of ataxia-telangiectasia (AT) with features of non-X-linked hyperIgM (HIGM)

Atypical clinical presentation of ataxia telangiectasia

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency with recurrent infections, IgA and IgE deficiency, and increased incidence of malignancies. The pathognomonic biological abnormalities consist of spontaneous chromosomal instability resulting in a high in vivo occurrence of cells with translocations, especially involving chromosomes 7 and 14, and a relative insensitivity of DNA replication in vitro to radiation exposure. We report on a patient with the biological hallmarks of AT but with atypical clinical manifestations. Although progressive cerebellar ataxia was present, the neurological picture was broader than that usually seen in AT and included peripheral polyneuropathy and spinal atrophy. On the other hand, telangiectasias, recurrent infections, malignancies, IgA deficiency, or other immunological abnormalities were not present. This illustrates that the clinical picture of AT is broad and nonspecific, and highlights the diagnostic value of cytogenetic analysis and studies of radioresistance of DNA synthesis.

Ataxia-telangiectasia Presenting with Craniostenosis

Ataxia-telangiectasia Presenting with Craniostenosis