Orphanet: Cernunnos XLF deficiency

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Cernunnos-XLF deficiency

ORPHA:169079

Classification level: Disorder

Synonym(s):
- 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
ICD-11: 4A01.1Y
OMIM: 611291
UMLS: C4303792
MeSH: -
GARD: -
MedDRA: -

Summary

Epidemiology

Prevalence is unknown. To date, five cases have been reported.

Clinical description

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).

Etiology

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.

Diagnostic methods

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 diagnosis

Differential diagnoses include Nijmegen breakage syndrome and LIG4 syndrome (see these terms).

Genetic counseling

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.

Prognosis

Without treatment, the immunodeficiency may result in severe infection, sepsis and early death.

Expert reviewer(s): Pr Andrew GENNERY - Last update: July 2012

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