Name: Nijmegen breakage syndrome | Acronym: NBS
Alt. names: Berlin breakage syndrome | Immunodeficiency-microcephaly-chromosomal instability syndrome | Ataxia-telangiectasia, variant 1

Gene: NBN | MOI: Autosomal recessive | Mechanism of action:

No. of cases in DB: 0 | First reported in: 1998

Last updated on: 2023-02-28 16:41:18 by

OMIM: 251260

Orphanet: 647

MONDO: -

DOID: -

ClinGen:

It is a rare genetic disease presenting at birth with microcephaly, dysmorphic facial features, becoming more noticeable with age, growth delay, and later-onset complications such as malignancies and infections. Prevalence and incidence are not known. 150 patients have been reported in the literature but many more are recorded in patient registries. The disease seems to occur worldwide, but has a much higher prevalence among Central and Eastern European Slavic populations due to a founder mutation. Clinical manifestations are not pathognomonic and may vary in severity. The main signs are microcephaly, present at birth and progressing with age, dysmorphic facial features (prominent midface emphasized by a sloping forehead and receding mandible). Other facial characteristics are more subtle and diverse, e.g. upwardly slanted palpebral fissures, long and beaked nose or short nose with anteverted upturned nostrils. In a few patients, cleft lip/palate or choanal atresia have been described. Mild growth retardation, and, in females, premature ovarian insufficiency are common. Minor skeletal anomalies, such as clinodactyly of the 5th fingers and partial syndactyly of the 2nd and 3rd toes are found (50% of patients). Delayed speech development is common. Café au lait spots and/or vitiligo spots are observed (50-70%). Hair in NBS is usually thin and sparse in infancy but improves with age. Hair greying can appear as early as in the 2nd or 3rd decade. Congenital renal anomalies (hypoplasia/aplasia, horseshoe or double kidney, ectopic/dystopic kidneys) are relatively frequent. Hypospadias, cryptorchidism, urethro-anal fistula are also found. Immune deficiency with recurrent respiratory tract infections that may be life-threatening and a strong predisposition to malignancies (predominantly lymphoid) and radiosensitivity are other integral manifestations. By age 20, over 40% of patients develop a malignant disease.

Description of management option has not been reviewed yet.