Definition: X-linked disease associating osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency.

Synopsis

 incontinentia pigmenti (IP)
 mild osteopetrosis
 unilateral lymphedema
 anhidrotic ectodermal dysplasia

• sparse hair
• facial dysmorphy
• delayed eruption of teeth
• sweat gland anomalies

 severe immunodeficiency

• multiple infections
  • Gram-negative (Salmonella enteritidis)
  • Gram-positive bacteria (Streptococcus pneumoniae)
  • nontuberculous mycobacteria (Mycobacterium kansasii)
  • Pneumocystis carinii

 alveolar proteinosis

Etiology

 germline mutations in IKBKG (NF-kappaB essential modulator) (MIM.300248)

References

 Smahi A, Courtois G, Rabia SH, Doffinger R, Bodemer C, Munnich A, Casanova JL, Israel A. The NF-kappaB signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromes. Hum Mol Genet. 2002 Oct 1;11(20):2371-5. PMID: #12351572#

 Dupuis-Girod S, Corradini N, Hadj-Rabia S, Fournet JC, Faivre L, Le Deist F, Durand P, Doffinger R, Smahi A, Israel A, Courtois G, Brousse N, Blanche S, Munnich A, Fischer A, Casanova JL, Bodemer C. Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother. Pediatrics. 2002 Jun;109(6):e97.

 Doffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, Bodemer C, Kenwrick S, Dupuis-Girod S, Blanche S, Wood P, Rabia SH, Headon DJ, Overbeek PA, Le Deist F, Holland SM, Belani K, Kumararatne DS, Fischer A, Shapiro R, Conley ME, Reimund E, Kalhoff H, Abinun M, Munnich A, Israel A, Courtois G, Casanova JL. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001 Mar;27(3):277-85. PMID: #11242109#