CHROMOSOMAL INSTABILITY AND IMMUNODEFICIENCY – ESSENTIAL FOR THE DIAGNOSIS OF NIJMEGEN SYNDROME

Joana Correia, Liliana Pinho, Isabel Couto Guerra, Emília Costa, Esmeralda Cleto

Abstract


Introduction: Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder that belongs to the group of chromosomal instability syndromes, more prevalent in Central and Eastern Europe.

Clinical case: We describe the case of a 14-month-old boy, born to Ukrainian parents, that presented at birth with microcephaly, small to gestational age and dysmorphic facial characteristics, which became more obvious with age. The complementary study revealed spontaneous and induced chromosomal instability, with normal fetal haemoglobin and α-fetoprotein and cellular immunodeficiency. These features suggested NBS, confirmed by the identification of the founder mutation (657del5) in homozygous state, common in patients of Slavic origin.

Discussion: NBS should be considered in the presence of microcephaly, typical facial features, growth retardation, chromosomal instability and immunodeficiency. The prognostic is poor due to the occurrence of frequent infections and the high incidence of cancer. Multidisciplinary follow-up and avoidance of radiation exposition are crucial.


Keywords


Nijmegen Breakage Syndrome; chromosomal instability; immunodeficiency

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References


Taylor AMR. Chromosome instability syndromes. Best

Practice Research Clinical Haematology. 2001; 14:631-44

Weemaes CM, Hustinx TW, Scheres JM, van Munster PJ,

Bakkeren JA, Taalman RD. A new chromosomal instability

disorder: the Nijmegen breakage syndrome. Acta Paediatr

Scand. 1981; 70:557–64.

Chrzanowska KH, gregorek H, Dembowska-Baginska B,

Kalina MA, Digweed M. Nijmegen Breakage Syndrome.

Orphanet Journal of Rare Diseases. 2012; 7:13.

The International Nijmegen Breakage Syndrome Study

Group. Nijmegen Breakage Syndrome. Arch Dis Child. 2000;

:400-6.

Chrzanowska K, Kalina M, Rysiewski H, Gajdulewicz M,

Szarras-Czapnik M, Gajtko-Metera M, et al. Growth pattern

in patients with Nijmegen breakage syndrome: evidence

from a longitudinal study [abstract]. Horm Res Paediatr.

; 74(Suppl 3):s38.

Chrzanowska KH, Szarras-Czapnik M, Gajdulewicz M,

Kalina MA, Gajtko-Metera M, Walewska-Wolf M, et al. High

prevalence of primary ovarian insufficiency in girls and

young women with Nijmegen breakage syndrome: evidence

from a longitudinal study. J Clin Endocrinol Metab. 2010;

:3133-40.

Bekiesińska-Figatowska M, Chrzanowska KH, Sikorska J,

Walecki J, Krajewska-Walasek M, Jóźwiak S. Cranial MRI

in the Nijmegen breakage syndrome. Neuroradiology. 2000;

:43–7.

Bekiesińska-Figatowska M, Chrzanowska KH, Jurkiewicz

E, Wakulińska A, Rysiewski H, Gładkowska-Dura M, et al.

Magnetic resonance imaging of brain anormalities in patients

with the Nijmegen breakage syndrome. Acta Neurobiol Exp.

; 64:503-9.

Gregorek H, Chrzanowska KH, Michalkiewicz J, Syczewska

M, Madalinski K. Heterogeneity of humoral immune

abnormalities in children with Nijmegen breakage syndrome:

an 8-year follow-up study in a single centre. Clin Exp

Immunol. 2002; 130:319–24.

Gregorek H, Chrzanowska KH, Dzierżanowska-Fangrat

K, Wakulińska A, Pietrucha B, Zapaśnik A, et al. Nijmegen

breakage syndrome: long-term monitoring of viral and

immunological biomarkers in peripheral blood before

development of malignancy. Clin Immunol. 2010;135: 440–7.

Pérez-Vera P, González-del Angel A, Molina B, Gómez

L, Frías S, Gatti RA, et al. Chromosome instability with

bleomycin and X-ray hypersensitivity in a boy with Nijmegen

breakage syndrome. Am J Med Genet. 1997; 70:24–7.

Chrzanowska KH, Stumm M, Bekiesińska-Figatowska M,

Varon R, Białecka M, Gregorek H, et al. Atypical clinical

picture of the Nijmegen breakage syndrome associated with

developmental abnormalities of the brain. J Med Genet.

; 38:E3.

Gennery AR, Slatter MA, Bhattacharya A, Barge D, Haigh S,

O’Driscoll M, et al. The clinical and biological overlap between

Nijmegen Breakage Syndrome and Fanconi anemia. Clin

Immunol. 2004; 113:214–9.

Ben-Omran TI, Cerosaletti K, Concannon P, Weitzman

S, Nezarati MM. A patient with mutations in DNA Ligase

IV: clinical features and overlap with Nijmegen breakage

syndrome. Am J Med Genet A. 2005; 137A:283–7.

Varon R, Seemanova E, Chrzanowska K, Hnateyko O,

Piekutowska-Abramczuk D, Krajewska-Walasek M, et al.

Clinical ascertainment of Nijmegen breakage syndrome

(NBS) and prevalence of the major mutation, 657del5, in

three Slav populations. Eur J Hum Genet. 2000; 8:900–2.


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