Search for a rare disease
Other search option(s)
Cernunnos-XLF deficiency is a rare form of combined immunodeficiency characterized by microcephaly, growth retardation, and T and B cell lymphopenia.
ORPHA:169079Classification level: Disorder
- Cernunnos XLFD
- Cernunnos deficiency
- Combined immunodeficiency-microcephaly-growth retardation-sensitivity to ionizing radiation syndrome
- NHEJ1 deficiency
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: D81.1
- OMIM: 611291
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
Prevalence is unknown. To date, five cases have been reported.
Patients present in childhood with growth retardation, microcephaly, uro-genital and bone malformations, dysmorphic features, including ''bird-like'' facial dysmorphism, and features of combined immunodeficiency including recurrent opportunistic, viral and bacterial infections. Some patients may also present with autoimmune cytopenia (anemia and thrombocytopenia). Patients share several clinical features with Nijmegen breakage syndrome and LIG 4 deficiency (see these terms).
This disease is caused by mutations in the NHEJ1 (or Cernunos) gene (2q35). The resulting defect of Cernunnos/XLF, a core protein of the non-homologous end-joining (NHEJ) pathway, affects the major mechanism of DNA double-strand break repair.
Diagnosis is based on the combination of clinical features with evidence of B and T cell lymphocytopenia with normal levels of natural killer (NK) cells. Fibroblasts also exhibit increased radiosensitivity.
Differential diagnoses include Nijmegen breakage syndrome and LIG4 syndrome (see these terms).
Transmission is autosomal recessive.
Management and treatment
Treatment is based on antibiotic treatment of infections, immunoglobulin replacement, antiviral prophylaxis and allogeneic hematopoietic stem-cell transplantation (HSCT). Radiotherapy as part of conditioning regimens should be avoided. Reduced intensity conditioning regimens are favored.
Without treatment, the immunodeficiency may result in severe infection, sepsis and early death.
- Summary information
- Polski (2012, pdf)