Skeletal dysplasia

Gene: IKBKG

Green List (high evidence)

X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5).

Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.

Created: 29 May 2022, 2:01 a.m. | Last Modified: 29 May 2022, 2:01 a.m.

Panel Version: 1.15

Well established gene-disease associations. MIM#300291 and 300636 represent part of a spectrum.

Note structural variants are common, as are mapping issues, so variant detection by NGS may be challenging.

Created: 17 Mar 2022, 11:32 p.m. | Last Modified: 17 Mar 2022, 11:32 p.m.

Panel Version: 0.11535

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Ectodermal dysplasia and immunodeficiency 1, MIM# 300291; Immunodeficiency 33 , MIM#300636; Incontinentia pigmenti, MIM# 308300; Autoinflammatory disease, systemic, X-linked, MIM# 301081

Publications

• 31874111
• 35289316