title: Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother.
abstract: A child with X-linked osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency (OL-EDA-ID) was recently reported. We report the clinical features of a second boy with this novel syndrome and his mother, who presented with signs of incontinentia pigmenti (IP). The child had mild osteopetrosis without neurosensory complications, unilateral lymphedema of the left leg, and characteristic features of anhidrotic ectodermal dysplasia with sparse hair, facial dysmorphy, delayed eruption of teeth, and sweat gland abnormalities. He died at 18 months of severe immunodeficiency with multiple infections caused by Gram-negative (Salmonella enteritidis) and Gram-positive (Streptococcus pneumoniae) bacteria, nontuberculous mycobacteria (Mycobacterium kansasii), and fungi (Pneumocystis carinii). His 30-year-old mother's medical history, together with residual cutaneous lesions, was highly suggestive of IP without neurologic impairment. In this patient with OL-EDA-ID, we detected the same NF-kappaB essential modulator stop codon hypomorphic mutation identified in the previous patient. The occurrence of the same clinical features in 2 unrelated patients with the same genotype demonstrates that OL-EDA-ID is a genuine clinical syndrome. The clinical and biological descriptions of the proband and his mother further corroborate the relationship between IP and EDA. Both syndromes are allelic and are associated with mutations in NF-kappaB essential modulator, with a genotype-phenotype correlation in hemizygous males. In contrast, loss-of-function mutations and hypomorphic mutations may cause IP in females.
authors.affiliation: Unité d'Immunologie et d'Hé matologie pédiatriques, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dupuis-Girod
authors.forename: Nadège
authors.initials: N
authors.lastname: Corradini
authors.forename: Smail
authors.initials: S
authors.lastname: Hadj-Rabia
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Fournet
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Philippe
authors.initials: P
authors.lastname: Durand
authors.forename: Rainer
authors.initials: R
authors.lastname: Döffinger
authors.forename: Asma
authors.initials: A
authors.lastname: Smahi
authors.forename: Alain
authors.initials: A
authors.lastname: Israel
authors.forename: Gilles
authors.initials: G
authors.lastname: Courtois
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Christine
authors.initials: C
authors.lastname: Bodemer
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000328:Adult; D000367:Age Factors; D018388:Codon, Terminator / Q000235:genetics; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D051550:I-kappa B Kinase; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000235:genetics*; D007184:Incontinentia Pigmenti / Q000175:diagnosis / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008209:Lymphedema / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D010022:Osteopetrosis / Q000175:diagnosis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012737:Sex Factors; D013577:Syndrome
chemical_list: D018388:Codon, Terminator; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human