Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother.
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.
Dupuis-Girod
Sophie
S
Unité d'Immunologie et d'Hé matologie pédiatriques, Hôpital Necker-Enfants Malades, Paris, France.
Corradini
Nadège
N
Hadj-Rabia
Smail
S
Fournet
Jean-Christophe
JC
Faivre
Laurence
L
Le Deist
Françoise
F
Durand
Philippe
P
Döffinger
Rainer
R
Smahi
Asma
A
Israel
Alain
A
Courtois
Gilles
G
Brousse
Nicole
N
Blanche
Stéphane
S
Munnich
Arnold
A
Fischer
Alain
A
Casanova
Jean-Laurent
JL
Bodemer
Christine
C
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
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