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| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 3
| Issue : 1 | Page : 33-38 |
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A clinical profile of 100 patients with ataxia telangiectasia seen at a tertiary care center
Manjunath Mahadevappa1, Nitish Kamble2, DV Santhosh Kumar3, Ravi Yadav2, M Netravathi2, Pramod Kumar Pal2
1 Department of Neurology, Manipal Hospitals, Bengaluru, Karnataka, India
2 Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
3 Sagar Hospital, Bengaluru, Karnataka, India
| Date of Submission | 01-Nov-2019 |
| Date of Decision | 23-Dec-2019 |
| Date of Acceptance | 26-Jan-2020 |
| Date of Web Publication | 01-Apr-2020 |
Correspondence Address:
Dr. Pramod Kumar Pal
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru 560029, Karnataka.
India
 Source of Support: None, Conflict of Interest: None  | 3 |
DOI: 10.4103/AOMD.AOMD_28_19
INTRODUCTION: Ataxia telangiectasia (AT) is an autosomal-recessive disease, characterized by progressive cerebellar degeneration, mucocutaneous telangiectasia, immunodeficiency, recurrent sinopulmonary infections, sensitivity to radiation, and increased risk of malignancy. The objective of this study was to report the clinical profile of a large cohort of patients with AT seen in a tertiary care referral center. METHODS: This study was a chart review of 100 patients with AT seen by the department of neurology at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India, which is a tertiary care referral center. Detailed demographic, clinical, laboratory, and electrophysiological data were collected from the case records. RESULTS: The mean age of presentation was 9.04 ± 3.52 years. Females (n = 40) had earlier age of presentation (8.87 ± 3.09 years) when compared to males (9.15 ± 3.80 years). The mean age for onset of illness was 3.9 ± 2.84 years, and the mean duration of illness was 4.81 ± 3.30 years. A positive family history was obtained in 20% and consanguinity in 60%. Oculomotor abnormalities included impaired pursuit and slow saccades in 60%, oculomotor apraxia in 84%, and nystagmus in 23%. All the patients had cerebellar ataxia. Extrapyramidal features such as dystonia, choreoathetosis, tremors, and myoclonus were observed in 31% of patients. CONCLUSION: Progressive cerebellar ataxia and telangiectasias were the consistent findings observed in all our patients. Dystonia and chorea were the other extrapyramidal features observed. Owing to increased risk of malignancies, screening should be an integral part of management. Keywords: Alpha-fetoprotein, ataxia, cerebellar ataxia, immunoglobulins, telangiectasia
How to cite this article:
Mahadevappa M, Kamble N, Santhosh Kumar D V, Yadav R, Netravathi M, Pal PK. A clinical profile of 100 patients with ataxia telangiectasia seen at a tertiary care center. Ann Mov Disord 2020;3:33-8 |
How to cite this URL:
Mahadevappa M, Kamble N, Santhosh Kumar D V, Yadav R, Netravathi M, Pal PK. A clinical profile of 100 patients with ataxia telangiectasia seen at a tertiary care center. Ann Mov Disord [serial online] 2020 [cited 2023 May 30];3:33-8. Available from: https://www.aomd.in/text.asp?2020/3/1/33/281742 |
| Introduction | |  |
Ataxia telangiectasia (AT) is a rare genetically determined progressive neurodegenerative disease caused by mutations in the ataxia telangiectasia mutated (ATM) gene.[1],[2] The gene codes for the protein kinase ATM, which plays an important role in deoxyribonucleic acid damage repair leading to loss of function.[3],[4],[5]
The first descriptions were published by Syllaba and Henner in 1926.[6] Progressive choreoathetosis and ocular telangiectasia were observed in a single family of three members. After 15 years, in 1941, Louis-Bar[2] described progressive cerebellar ataxia and cutaneous telangiectasia in a Belgian child. The syndrome subsequently received the name of Louis-Bar.[2] Progressive cerebellar ataxia and oculocutaneous telangiectasia are the diagnostic hallmark of AT.
It is a highly pleiotropic primary immunodeficiency disorder, inherited in an autosomal-recessive manner. In addition to progressive neurodegeneration, patients have a tendency to develop severe bronchial complications, cellular and humoral immunodeficiency, increased risk of malignancies, hypersensitivity to radiation, and lung disease.[7] AT is reported in all regions of the world with a reported incidence of 1 of 88,000 live births in the United States. Onset of symptoms is usually between 2 and 5 years; however, can be seen in infancy also.[8] The frequency of heterozygosity of AT mutant allele was reported to be 1.4%–2% of the general population.[9] AT has no sex predilection.[10] Even though with recent advances in research, the number of potential options for treating patients with AT exists, at present no therapy is available to cure or prevent the progression.[7]
In India, literature on AT is limited to only case reports and small series.[11],[12],[13] Owing to its wide clinical heterogeneity, it often leads physicians to an incorrect or missed diagnosis, and insight into this rare disease is important. The objective of this study was to report the clinical profile of a large cohort of patients with AT seen in a tertiary care referral center.
| Methods | | |
This study was a chart review of 100 patients with AT observed at the department of neurology at the National Institute of Mental Health and Neurosciences (NIMHANS), which is a tertiary care referral center. The diagnosis of AT was made by movement disorders specialists. It was based on clinical history of progressive cerebellar ataxia in a child, presence of oculocutaneous telangiectasias with or without elevated serum alpha-fetoprotein (AFP) levels. Patients with microcephaly, severe mental retardation, and nonprogressive ataxia were excluded from the study.
All the relevant demographic, clinical, laboratory, and electrophysiological data were collected from the case records and entered in a pro forma. Increased AFP level more than twice the upper limit of normal range (>40ng/dL) was considered significant. Blood samples were tested to quantitate the immunoglobulin levels using nephelometry methods in some patients.
Data were analyzed using the R software (R 3.5.3. R Development Core Team). Data were expressed as mean and standard deviation for continuous variables and frequency (percentage) for categorical variables.
| Results | | |
A total of 100 patients with AT (60 males and 40 females) were evaluated.
- Demographic characteristics: The mean age of presentation was 9.04 ± 3.52 years. Females had earlier age of presentation (8.87 ± 3.09 years) when compared to males (9.15 ± 3.80 years). The mean age of onset of illness was 3.9 ± 2.84 years, and the mean duration of illness was 4.81 ± 3.30 years [Table 1]. A positive family history was obtained in 20% and consanguinity in 60%. Majority (96%) had normal birth history, 26% had delayed motor milestones because of truncal ataxia and delayed walking, and 11% had delayed mental milestones.
- Clinical characteristics: Cerebellar ataxia was present in all the patients at presentation. Other features observed were dysarthria (90%), recurrent sinopulmonary infections (64%), and dystonia or choreoathetosis (29%). One patient presented with dystonic crisis. None of our patients had motor weakness or spasticity. Majority of patients had prior history of recurrent sinopulmonary infections, pulmonary tuberculosis, and few had febrile seizures. On general physical examination, ocular telangiectasia was present in all [Figure 1]. Few patients (<5%) had other dermatological manifestations such as café au lait spots, hypopigmented macules, vitiligo, and seborrheic dermatitis. Skeletal deformities, such as kyphoscoliosis, were observed in six patients, and one patient had valgus deformity of knee and ankle, pes cavus, winging of scapula, and arachnodactyly. Nine percent patients were wheelchair bound at presentation. Neurological examination revealed oculomotor abnormalities in the form of impaired pursuit and slow saccades in 60%, oculomotor apraxia in 84%, and nystagmus in 23%. Hypotonia was observed in 68% and hyporeflexia or areflexia in 61%; however, no significant wasting of muscles was noted. Fine touch and pinprick sensations were normal. Approximately 31% patients had extrapyramidal features in the form of dystonia, choreoathetosis, and tremors. Head titubation was observed in 41%. All patients had appendicular incoordination and gait ataxia. Positive Romberg’s test was observed in 5% [Table 2]. Detailed neuropsychological testing and intelligence quotient (IQ) testing was not performed in any of our patients.,
- Investigations: Routine blood investigations were normal in majority of the patients. Two patients had anemia (iron deficiency anemia) and one patient had mild elevation of liver enzymes. Low immunoglobulin levels were present in 15 of 28 patients tested (53.6%). Low immunoglobulin (Ig) M levels were observed in 1, low IgE in 2, and low IgA in 13 patients. One patient had combined deficiency of IgA, IgG, and IgM. Elevated AFP levels were observed in 39 of 47 patients tested (83.0%). One patient developed Burkitt lymphoma on follow-up. Genetic testing was not performed for any of the patients. Data on nerve conduction study were available for 29 patients. Approximately 44.8% patients showed evidence of mixed sensory > motor neuropathy (asymptomatic, axonal type). Neuroimaging was performed in 48 patients that included magnetic resonance imaging for 17 patients and computed tomography (CT) of brain for 31 patients (CT was carried out by the referring physician and not at our institute). Approximately 62.5% showed mild to severe cerebellar atrophy. One patient was found to have oxycephaly. Seventy-four patients presented in the first decade and twenty-six patients in the second decade. No difference was observed in terms of severity of the disease between the two groups. However, in patients who presented in the first decade, extrapyramidal symptoms were observed in 27.1% (choreoathetosis, 13.5% and dystonia, 8.1%), and in patients who presented in the second decade, they were observed in 26.9% (choreoathetosis, 15.4% and dystonia, 11.5%). Skeletal deformities were observed in 23.1% patients who presented in second decade (10.8% in the other group). Anemia was observed in 5.4% patients who presented in the first decade and none in the other group. No biochemical abnormalities were observed in the groups.
| Discussion | | |
From the available literature, it is evident that AT has typical and atypical presentations, with both mild and severe forms, childhood- or adult-onset forms have been described. In the literature, various atypical clinical forms, including those without oculocutaneous telangiectasia, have been reported.[8]
AT was first described in India by Dogra and Manchanda.[14] Indian literature on AT is limited only for case reports and series.[11],[12],[13]
In this study, we describe clinical profile of 100 patients diagnosed with AT. This is the largest series from India till date. Two cases of AT were described by Verma et al.,[15] from a cohort of 27 patients with primary immunodeficiency disorders in children with mean age of 5.4 ± 4.6 years (2 months to 16 years) over a period of 24 months at a tertiary care hospital in northern India. Gender predilection of this disease is not known; however, in our study, a mild male predominance was observed (3:2).[10],[16] As majority of our patients belonged to Karnataka state, it could be due to the easy accessibility to our center.
Patients commonly present with neurological symptoms. However, a case of 6-year-old girl with AT has been reported who did not have neurological involvement.[17] Alterman et al.[18] reported mild neurological clinical presentation among two siblings with AT. In our study, cerebellar ataxia was seen in all the patients at presentation. The age at onset in our patients is comparable to other studies.[19] Majority of the patients become wheelchair bound by 10–11 years.[20] Some studies have also reported later onset and slower progression.[21],[22] The oldest patient observed in our study was 24 years old with onset at 12 years of age.
Consanguinity may increase the risk of autosomal-recessive disorders.[23] Consanguinity has been reported in 33% of marriages in south India, and 29.7% are in Karnataka state, from where majority of our patients come.[24] In our study, consanguinity was observed in 60%. It was 81.1% (60 of 74 patients with AT) among Iranian primary immunodeficient patients.[25] Parental consanguinity was reported in 79 families among 104 patients with AT in a study by Moin et al.[19] in an Iranian cohort, where the overall rate of consanguineous marriage was 38.6%. Positive family history of 20% was observed in our study. Some studies have shown higher rate of familial incidence (45%).[26] Educating society about the possible hazards of consanguineous marriage is crucial in reducing the incidence of these fatal genetic diseases.
The clinical features observed in our study have been reported in previous studies [Table 3]. Telangiectasia consists of dilated venules, noted over the bulbar conjunctiva and observed in almost all the patients of AT. They can also be found on the external ear lobe, eyelid, flexure folds of neck, antecubital and popliteal fossa, palate, or over the entire body, which may reflect progeric changes of the skin.[27] Clinically, it presents after the onset of ataxia, with a latency of 3–6 years.[10],[20] Ocular telangiectasia was observed in all our patients. Many studies are available that have shown variability in the occurrence of telangiectasia. Ocular and cutaneous telangiectasias were present in 87% and 73% patients, respectively, in the Iranian study.[19] Two variant cases with onset at ages 3 and 4 years without telangiectasia have also been described.[28] Taylor et al.[29] described three patients with “minimal” telangiectasias. This clinical heterogeneity of AT is known. This may be due to phenotypical variation from a common gene, different alleles of the same gene, or varying combinations of tightly linked genes.[30] Cutaneous abnormalities such as gray hair, vitiligo, café au lait spots, and scleroderma-like changes, seborrheic dermatitis of the scalp, hirsutism, senile keratosis, and basal cell carcinoma are also reported among patients with AT.[27] Some of our patients had similar findings. | Table 3: Comparison of clinical profile of patients in present study with other studies
Click here to view |
The observation that mental deficiency is not characteristic of AT in younger children is supported by most reports in literature.[10] In our patients, 11% had delayed mental milestones as reported by their parents. Detailed neuropsychological testing and IQ testing was not performed in our cohort. However, the results of psychometric testing showed wide scatter, and the IQ scores tended to drop below normal range as the disease progresses. In a tabular analysis of 101 cases, ranging in age from 5 to 18 years, mental deficiency emerged as a rather frequent feature at 33%,[26] and among Iranian study, it was nearly 10%. Reason could be due to high rate of consanguinity seen in all the three studies.
Choreoathetosis as the most common extrapyramidal feature has been reported in 90% of cases.[26],[31] In our study, it was in 29%. Severe choreoathetosis can initially mask the presence of ataxia.[32] This feature, as noted in the first published descriptions of AT by Syllaba and Henner,[6] provides a disturbing reminder that not all neurological symptoms in AT implicate the cerebellum as the central lesion. Dystonia usually develops as a late manifestation and is reported in 71% of patients.[31] Dystonia as a presenting feature is very rare. Goyal and Behari[13] reported a case in a 13-year-old girl from India, where dystonia was the presenting feature even before onset of cerebellar symptoms.[13] In our series, one patient came in dystonic crisis and underwent pallidotomy when medical management failed. Dystonia is rare among adolescents and adult patients with AT.[33],[34] Pathogenesis of dystonia is not clear. Proposed hypothesis for dystonia among patients with AT, which needs to be tested is due to vascular abnormality in basal ganglia or secondary changes in basal ganglia due to altered hemodynamics secondary to vascular abnormality in nearby parenchyma.[13] Myoclonus is rare among AT. Myoclonus has been described in 16 of 70 patients in a series by Woods and Taylor.[31] Myoclonus was not observed in our patients; however, subsequent follow-up of these patients would have given information, which was lacking in our study. Oculomotor apraxia was more frequent (84%) in our study, which was in concordance with other studies.
Immunodeficiency is a characteristic feature of AT seen in 60%–80%. It involves both humoral and cellular immunodeficiency. The most striking and consistent immunological defects in AT are abnormal or absent thymus, defect in cellular immunity, notably impairment of delayed hypersensitivity and impaired ability to reject skin graft, and dysgammaglobulinemia with decreased serum IgA and IgE. In our study, low immunoglobulin levels were observed in 53.6%. In an Indian series of 22 patients, IgG was normal in all patients but IgM was low in 2 of 18 patients that were tested.[35] No difference was observed in the patient population with and without immunoglobulin deficiency.
The major causes of mortality among patients with AT are infection and malignancy. However, previous studies have found little correlation between clinical immunodeficiency manifesting as frequent sinopulmonary infection and immunoglobulin deficiency.[36] In Boder and Sedgwick[26] autopsy review of 58 cases, 27 (46%) deaths were caused by pulmonary infection alone, 12 (21%) by malignancy alone, 16 (28%) by a combination of both, and 3 (5%) by other reasons. With the available data in our study, recurrent sinopulmonary infections (64%) were seen among those with low immunoglobulins levels, which was comparable with other studies. The frequency of infections, infective organisms, and the associated mortality was not available in our records.
The lifetime risk of cancer among patients with AT is 10%–38%.[37],[38],[39] In our study, only one patient had Burkitt lymphoma. The true prevalence of malignancies in our cohort was not available due to lack of follow-up.
High AFP levels along with low IgA levels are useful screening test for AT diagnosis with sensitivity of more than 95%.[37] Significantly elevated serum AFP level is a useful screening test for AT. As with phenotypic variations of the disease, variations in laboratory abnormalities are also observed. Patients of AT with normal serum AFP have previously been described.[19],[40],[41] In our study, normal AFP levels were seen in 8 of 47 patients (17%). A grossly elevated AFP level in a patient with known AT may indicate hepatitis, liver, or gonadal malignancy.
Neuropathy is a late manifestation in AT. In a series by Kwast and Roman,[42] electrophysiological examinations of 32 children aged 3–17 years, who had typical clinical manifestations of AT, showed generalized, progressive, sensory degeneration, with neurogenic amyotrophy affecting the distal part of the lower limbs. These findings were similar to our study. In the presence of neuropathy, Friedreich’s ataxia is a close differential diagnosis. Elevated AFP, the presence of telangiectasia, and the absence of posterior column dysfunction usually help to differentiate.[43]
Imaging studies usually show cerebellar atrophy. It helps in identifying structural causes in early stage of disease where telangiectasia is not yet apparent. Radiosensitive nature of disease should alert evaluating physician in choosing the appropriate investigative modality.
Many limitations were present in our study. The genetic confirmation was not carried out in our patients. Owing to lack of follow-up in our cohort, information about the emergence of various movement disorder phenomenologies, malignancy, morbidity, and mortality could not be captured.
| Conclusion | | |
This is the largest series of AT from India. A high prevalence of consanguinity (60%) was observed in our cohort. It warrants for genetic counseling to reduce the burden of this disease in the community. Progressive cerebellar ataxia and telangiectasias were the consistent findings observed in all our patients. Dystonia and chorea were the extrapyramidal features observed. As these patients are at increased risk of malignancies, screening should be an integral part of their management.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Woods CG, Bundey SE, Taylor AMR. Unusual features in the inheritance of ataxia telangiectasia. Human Genet 1990;84:555-62.  |
| 2. | Louis-Bar D. Sur un syndrome progressif comprenant des telengiectasias capillaries cutanees et conjunctivales symetriques disposition naevoide et des troubles cerebelleaux. Confin Neurol (Basel) 1941;4:32-41. |
| 3. | Crawford TO, Shiloh Y. Ataxia-telangiectasia. In: Brice A, Pulst SM, editors. Spinocerebellar Degenerations. The Ataxias and Spastic Paraplegias. Philadelphia, PA: Butterworth Heinemann Elsevier; 2007. pp. 202-21. |
| 4. | Treuner K, Barlow C. Ataxia-telangiectasia. In: Pulst SM, editor. Genetics of Movement Disorders. San Diego, CA: Academic Press; 2003. pp. 195-203. |
| 5. | Sahama I, Sinclair K, Pannek K, Lavin M, Rose S. Radiological imaging in ataxia telangiectasia: A review. Cerebellum 2014;13:521-30. |
| 6. | Syllaba L, Henner K. Contribution a l,independence de l,athethose double idiopathiqe et congenitale. Rev Neurol 1926;1:541-62. |
| 7. | Lavin MF, Gueven N, Bottle S, Gatti RA. Current and potential therapeutic strategies for the treatment of ataxia-telangiectasia. Br Med Bull 2007;81-82:29-47. |
| 8. | Teive HA, Moro A, Moscovich M, Arruda WO, Munhoz RP, Raskin S, et al. Ataxia-telangiectasia—A historical review and a proposal for a new designation: ATM syndrome. J Neurol Sci 2015;355:3-6. |
| 9. | Swift M, Morrell D, Cromartie E, Chamberlin AR, Skolnick MH, Bishop DT. The incidence and gene frequency of ataxia-telangiectasia in the United States. Am J Hum Genet 1986;39:573-83. |
| 10. | Gatti RA. Ataxia-telangiectasia. Dermatol Clin 1995;13:1-6. |
| 11. | Goel M, Singh A, Dwivedi R. Ataxia telangiectasia: A case report. 2015;5:578-80. |
| 12. | Kashinakunti MD, Dhananjaya M. Ataxia telangiectasia case report from tertiary-care hospital of north Karnataka. Medica Innovatica 2013:2:112-4. |
| 13. | Goyal V, Behari M. Dystonia as presenting manifestation of ataxia telangiectasia: A case report. Neurol India 2002;50:187. [ PUBMED] [Full text] |
| 14. | Dogra KN, Manchanda SS. Ataxia telangiectasia. Indian Pediatr 1967;4:354-7. |
| 15. | Verma S, Sharma PK, Sivanandan S, Rana N, Saini S, Lodha R, et al. Spectrum of primary immune deficiency at a tertiary care hospital. The Ind J Ped 2008;75:143-8. |
| 16. | Chiu BSK, Lau VWS, Huen KF. Ataxia telangiectasia: Case report of three affected brother and review of the literature. HK J Paediatr 2003;8:187-91. |
| 17. | Trimis GG, Athanassaki CK, Kanariou MM, Giannoulia-Karantana AA. Unusual absence of neurologic symptoms in a six-year old girl with ataxia-telangiectasia. J Postgrad Med 2004;50:270-1. [ PUBMED] [Full text] |
| 18. | Alterman N, Fattal-Valevski A, Moyal L, Crawford TO, Lederman HM, Ziv Y, et al. Ataxia-telangiectasia: Mild neurological presentation despite null ATM mutation and severe cellular phenotype. Am J Med Genet A 2007;143A:1827-34. |
| 19. | Moin M, Aghamohammadi A, Kouhi A, Tavassoli S, Rezaei N, Ghaffari SR, et al. Ataxia-telangiectasia in Iran: Clinical and laboratory features of 104 patients. Pediatr Neurol 2007;37:21-8. |
| 20. | Perlman S, Becker-Catania S, Gatti RA. Ataxia-telangiectasia: Diagnosis and treatment. Semin Pediatr Neurol 2003;10:173-82. |
| 21. | Byrne E, Hallpike JF, Manson JI, Sutherland GR, Thong YH. Ataxia-without-telangiectasia. Progressive multisystem degeneration with IgE deficiency and chromosomal instability. J Neurol Sci 1984;66:307-17. |
| 22. | Maserati E, Ottolini A, Veggoitte P, Lanzi G, Pasquali F. Ataxia without telangiectasia in two sisters with rearrangement of chromosomes 7 and 14. Clin Genet 1988;34:283-7. |
| 23. | Bittles A. Consanguinity and its relevance to clinical genetics. Clin Genet 2001;60:89-98. |
| 24. | Radha Rama Devi A, Rao NA, Bittles AH. Inbreeding in the state of Karnataka, south India. Hum Hered 1982;32:8-10. |
| 25. | Rezaei N, Pourpak Z, Aghamohammadi A, Farhoudi A, Movahedi M, Gharagozlou M, et al. Consanguinity in primary immunodeficiency disorders; the report from Iranian primary immunodeficiency registry. Am J Reprod Immunol 2006;56:145-51. |
| 26. | Boder E, Sedgwick RP. Ataxia telangiectasia: A review of 101 cases. In: Walsh G, editor. Little Club Clinics in Developmental Medicine. No.8. London, UK: Heinemann Books; 1963. pp. 110-8. |
| 27. | Porras O, Arguendas O, Arata M, Barrantes M, Gonzalez L, Saenz E. Epidemiology of ataxia telangiectasia in Costa Rica. In: Gatti RA, Painter RB, editors. Ataxia Telangiectasia. Heidelberg, Germany: Springer-Verlag; 1993. pp. 199-208. |
| 28. | Stell R, Bronstein AM, Plant GT, Harding AE. Ataxia telangiectasia: A reappraisal of the ocular motor features and their value in the diagnosis of atypical cases. Mov Disord 1989;4:320-9. |
| 29. | Taylor AM, Flude E, Laher B, Stacey M, McKay E, Watt J, et al. Variant forms of ataxia telangiectasia. J Med Genet 1987;24:669-77. |
| 30. | Ying KL, Decoteau WE. Cytogenetic anomalies in a patient with ataxia, immune deficiency, and high alpha-fetoprotein in the absence of telangiectasia. Cancer Genet Cytogenet 1981;4:311-7. |
| 31. | Woods CG, Taylor AMR. Ataxia telangiectasia in the British Isles: The clinical and laboratory feature of 70 affected individuals. QJM 1992;298:169-79. |
| 32. | Boder E, Sedgwick RP. Ataxia telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infections. Univ SC Med Bull 1958;9:15-22. |
| 33. | Amromin GD, Boder E, Teplitz R. Ataxia telangiectasia with a 32 years survival. A clinicopathological report. J Neuropath Exp Neurol 1979;38:621-43. |
| 34. | Sedgwick RP, Boder E. Ataxia telangiectasia. In: Vinken PJ Bruyn GW, editors. Handbook of Clinical Neurology. Vol. 14. Amsterdam, The Netherlands: North-Holland Publishing; 1972. pp. 267-339. |
| 35. | Datta U, Sehgal S, Kumar L, Kaur KJ, Walia BN, Chopra JS, et al. Immune status in ataxia telangiectasia. Indian J Med Res 1991;94:252-4. |
| 36. | Boder E. Ataxia-telangiectasia: An overview. Kroc Found Ser 1985;19:1-63. |
| 37. | Waldman TA, Mclntire KR. Serum-alfa-fetoprotein levels in patients with ataxia telangiectasia. Lancet 1972;2:1112-5. |
| 38. | Morrell D, Chase CL, Swift M. Cancers in 44 families with ataxia-telangiectasia. Cancer Genet Cytogenet 1990;50:119-23. |
| 39. | Spector B, Filipovich A, Perry G. Epidemiology of cancer in ataxia-telangiectasia. In: Bridges BA, Harnden DG, editors. Ataxia Telangiectasia: A Cellular and Molecular Link between Cancer, Neuropathology, and Immune Deficiency. Chichester, UK: Wiley; 1982. pp. 103-37. |
| 40. | Gatti RA, Bick M, Tam CF, Medici MA, Oxelius VA, Holland M, et al. Ataxia-telangiectasia: A multiparameter analysis of eight families. Clin Immunol Immunopathol 1982;23:501-16. |
| 41. | Kojis TL, Schreck RR, Gatti RA, Sparkes RS. Tissue specificity of chromosomal rearrangements in ataxia-telangiectasia. Hum Genet 1989;83:347-52. |
| 42. | Kwast O, Roman I. Progressive peripheral neuron degeneration in ataxia‐telangiectasia: An electrophysiological study in children. Dev Med Ch Neurol 1990;32:800-7. |
| 43. | Baloh RW, Yee RD, Boder E. Eye movements in ataxia-telangiectasia. Neurology 1978;28:1099-104. |
[Figure 1]
[Table 1], [Table 2], [Table 3]
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