Attenuated presentation of ataxia-telangiectasia with familial cancer history

Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: A genotype-phenotype study

“…In patients of group 3, immunoglobulin deficiency was not encountered at all. In the literature, only one patient with a milder A-T phenotype has been described with decreased IgA, IgG2, and IgG4 levels [Simonin et al, 2008]. Our observations, that a low level of residual ATM kinase activity leads to a less severe immunological phenotype than seen in patients without ATM kinase activity, are in line with data reported by Staples et al [Staples et al, 2008].…”

“…In recent years, it has become increasingly clear that the clinical phenotype of A-T varies from the severe, early-onset classical phenotype as described above to an adult-onset disorder with milder neurological impairment and less systemic symptoms [Hiel et al, 2006;Saviozzi et al, 2002;Silvestrim et al, 2010;Simonin et al, 2008;Stankovic et al, 1998;Sutton et al, 2004;. It has been postulated that the presence of some residual ATM kinase activity may protect the patient from the most severe, that is, "classical" disease course [Stewart et al, 2001;Verhagen et al, 2009a] In this study, we describe a relatively large series of A-T patients and focus on genotype-phenotype correlations.…”

The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia

“…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.…”

“…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.…”

Clinical spectrum of ataxia-telangiectasia in adulthood

“…some residual ATM kinase activity whereas ATM kinase activity is fully absent in patients with classic A-T. 4 The clinical features of genetically proven variant A-T have only been described in reports on single cases or on 2 families maximally, [6][7][8][11][12][13][14][15][16][17] while 4 other studies described primarily the genotypes of relative large series of patients with variant A-T. 9,10,18,19 We analyzed the clinical spectrum and genotype of a relatively large series of 13 adult patients with variant A-T and compared them with 6 patients with classic A-T who survived into adulthood. Aims of the study were to assess a possible genotype-phenotype relationship for mutations in the ATM gene and to facilitate early diagnosis by enhancing awareness of variant A-T.…”