Seeman Pavel, Gebertová Katerina, Paderová Katerina, Sperling Karl, Seemanová Eva
Department of Child Neurology, Charles University Hospital, Motol Prague, Czech Republic.
Pediatr Neurol. 2004 Mar;30(3):195-200. doi: 10.1016/j.pediatrneurol.2003.07.003.
The Nijmegen breakage syndrome is a rare autosomal recessive chromosomal instability disorder characterized by early growth retardation, congenital microcephaly, immunodeficiency, borderline mental development, and a high tendency to lymphoreticular malignancies. Most Nijmegen breakage syndrome patients are of Slavonic origin, and all of them known so far carry a founder homozygous 5 nucleotide deletion in the NBS1 gene. Microcephaly was present in 100% of Nijmegen breakage syndrome patients in a recent large international cooperative study. The frequency of Nijmegen breakage syndrome among children with primary microcephaly was not known. Early correct diagnosis of the syndrome is crucial for appropriate preventive care and therapy. We tested 67 Czech patients of different ages with simple microcephaly for the presence of the most common mutation in the NBS1 gene. Three new Nijmegen breakage syndrome cases were detected in this cohort, representing 4.5% of the cohort. All these newly diagnosed Nijmegen breakage syndrome patients were younger than 10 months at the time of diagnosis. They were all born within a 2.5-year period. Twenty-three of the 67 children in the cohort were born within this 2.5-year period, representing a 13% incidence of Nijmegen breakage syndrome. Frequency of Nijmegen breakage syndrome heterozygotes among infants in the Czech Republic is 1: 130-158 and the birth rate is 90,000 per year, therefore in the time span of 2.5 years, three new Nijmegen breakage syndrome homozygotes are expected to be born. Therefore we assume that by DNA testing of Czech primary microcephalic children it is possible to detect all Nijmegen breakage syndrome patients to be expected. The age at correct diagnosis was lowered from 7.1 years at the time before DNA testing, to well under 1 year of age. All new Nijmegen breakage syndrome patients could receive appropriate preventive care, which should significantly improve their life expectancy and prognosis.
奈梅亨断裂综合征是一种罕见的常染色体隐性染色体不稳定疾病，其特征为早期生长发育迟缓、先天性小头畸形、免疫缺陷、边缘智力发育以及患淋巴网状恶性肿瘤的倾向较高。大多数奈梅亨断裂综合征患者源自斯拉夫民族，且迄今为止已知的所有患者在NBS1基因中都携带一个由5个核苷酸缺失导致的奠基者纯合突变。在最近一项大型国际合作研究中，100%的奈梅亨断裂综合征患者都有小头畸形。原发性小头畸形儿童中奈梅亨断裂综合征的发病率尚不清楚。该综合征的早期正确诊断对于适当的预防护理和治疗至关重要。我们对67名不同年龄的捷克单纯小头畸形患者进行了检测，以确定其NBS1基因中最常见的突变情况。在该队列中检测到3例新的奈梅亨断裂综合征病例，占该队列的4.5%。所有这些新诊断出的奈梅亨断裂综合征患者在诊断时年龄均小于10个月。他们均在2.5年的时间段内出生。该队列中的67名儿童中有23名在这2.5年的时间段内出生，奈梅亨断裂综合征的发病率为13%。捷克共和国婴儿中奈梅亨断裂综合征杂合子的频率为1:130 - 158，且每年的出生率为90000，因此在2.5年的时间跨度内，预计会有3名新的奈梅亨断裂综合征纯合子出生。因此我们认为，通过对捷克原发性小头畸形儿童进行DNA检测，有可能检测出所有预期的奈梅亨断裂综合征患者。正确诊断的年龄从DNA检测前的7.1岁降低到了1岁以下。所有新的奈梅亨断裂综合征患者都能接受适当的预防护理，这应能显著提高他们的预期寿命和预后。
