Nijmegen Breakage Syndrome Differential Diagnoses

Updated: Jun 19, 2018
  • Author: Krystyna H Chrzanowska, MD, PhD; Chief Editor: William D James, MD  more...
  • Print
DDx

Diagnostic Considerations

Table 1.Syndromes to be Considered in the Differential Diagnosis of Nijmegen Breakage Syndrome (Open Table in a new window)

Clinical and Cellular Phenotype

Nijmegen Breakage Syndrome

Nijmegen Breakage Syndrome‒Like Disorder  [35, 76]

DNA LIG4 Deficiency  [33, 34, 77]

NHEJ1 Syndrome  [36, 37]

XRCC4 Deficiency  [38, 39]

Fanconi Anemia  [43, 44, 78]

Warsaw Breakage Syndrome  [79, 80]

Bloom Syndrome  [81, 82]

Online Mendelian Inheritance in Man (OMIM)

251260

604040

606593

611291

616541

227650

613398

210900

Gene

NBN

RAD50

DNA LIG4

NHEJ1

XRCC4

FANCa

DDX11

RECQL3

Microcephaly

Severe, disproportionate

Severe

Severe

Severe

Severe

In ~30%

Severe, disproportionate

Severe, proportionate

Growth Deficiency

Mild to moderate

Severe

Moderate to severe

Severe

Severe, disproportionate

Mild to moderate

Severe

Severe

Congenital Malformations

Heart, kidney, polydactyly

Not reported

Polydactyly, syndactyly

Polydactyly

Not reported

Heart, kidney radial bone defects (~50%)

Heart

Kidney, polydactyly

Puberty and Fertility

Primary amenorrhea (hypergonadotropic hypogonadism)

Normal puberty

Amenorrhea

Not reported

Primary amenorrhea

Males, infertility; females, early menopause

Normal puberty

Males, infertility; females, early menopause

Other Endocrinologic Problems

Not reported

Not reported

Hypothyroidism, type 2 diabetes

Not reported

Early-onset metabolic syndrome

Type 2 diabetes mellitus

Not reported

Type 2 diabetes mellitus

Recurrent Infections

Yes

No

Rare

Yes

No

No

No

Yes

Immunodeficiency

Combined (B- and T-cell)

No

Combined (B- and T-cell)

Combined (B- and T-cell)

No

No

No

B-cell type

Hematologic Findings

Myelodysplastic syndrome (incidentally)

Not reported

Pancytopenia, myelodysplastic syndrome

Pancytopenia, myelodysplastic syndrome

Thrombocytopenia, pancytopenia

Progressive bone marrow failure, myelodysplastic syndrome

Not reported

Myelodysplastic syndrome

Malignancy Type

Predominantly lymphoid origin

Not reported

Predominantly lymphoid origin

Not reported

Tumor

Acute myeloid leukemia, solid tumors (early onset)

Not reported

Lymphoid origin, acute myeloid leukemia, solid tumors

Chromosomal Instability

Breakages, including 7/14 rearrangements

Breakages, 7/14 rearrangements

Breakages, no 7/14 rearrangements

Breakages, not specified

Not reported

Breakages, figures (asymmetric)

Breakages and cohesinopathy

Breakages, figures (symmetric), high sister chromatid exchange rate

Sensitivity to Damaging Agents (in vitro)

Ionizing radiation, bleomycin; mitomycin C and diepoxybutane, mild

Ionizing radiation, bleomycin

Ionizing radiation, bleomycin

Ionizing radiation (variable)

Ionizing radiation (extreme)

Mitomycin C and diepoxybutane; ionizing radiation, mild

Mitomycin C, camptothecin

Ultraviolet

Mental Retardation

Mild to moderate

Moderate

Mild to moderate

Yes, not defined

Moderate to severe

Moderate to severe

Moderate to severe

Normal to mild

aFANC: Genetic and phenotypic heterogeneity; 19 genes known (OMIM).

Also consider the following:

  • Autosomal recessive primary microcephaly (MCPH), genetic and phenotypic heterogeneity (OMIM 17 entries): Defined by primary microcephaly over -3 standard deviations below the mean and various neurological problems (eg, spasticity, motor disability, mental retardation)
  • Seckel syndrome spectrum disorders (SCKS), genetic and phenotypic heterogeneity (OMIM 10 entries): Defined by severe primary microcephaly, severe prenatal and postnatal growth restriction, multiple various congenital malformations, and/or metabolic/biochemical features

Differential Diagnoses