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PEDIATRICS Vol. 109 No. 6 June 2002, pp. e97

ELECTRONIC ARTICLE

Osteopetrosis, Lymphedema, Anhidrotic Ectodermal Dysplasia, and Immunodeficiency in a Boy and Incontinentia Pigmenti in His Mother

Sophie Dupuis-Girod, MD^*,, Nadège Corradini, MD^*, Smail Hadj-Rabia, MD, Jean-Christophe Fournet, MD^||, Laurence Faivre, MD^¶, Françoise Le Deist, MD, PhD^**,, Philippe Durand, MD, Rainer Döffinger, PhD^||||, Asma Smahi, PhD^¶, Alain Israel, PhD^¶¶, Gilles Courtois, MD, PhD^¶¶, Nicole Brousse, MD^||, Stéphane Blanche, MD^*,||||, Arnold Munnich, MD, PhD^¶, Alain Fischer, MD, PhD^*,, Jean-Laurent Casanova, MD, PhD^*,|||| and Christine Bodemer, MD, PhD

^* Unité d’Immunologie et d’Hé matologie pédiatriques, Hôpital Necker-Enfants Malades, Paris, France
Unité d’Immunologie et d’Hématologie Pédiatriques, Hôpital Debrousse, Lyon, France
Service de Dermatologie, Hôpital Necker-Enfants Malades, Paris, France
^|| Service d’Anatomopathologie, Hôpital Necker-Enfants Malades, Paris, France
^¶ Unité de recherche sur les Handicaps Génétiques de l’Enfant, INSERM U393, Hôpital Necker-Enfants Malades, Paris, France
^** Laboratoire d’Immunologie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France
Développement Normal et Pathologique du système immunitaire, INSERM U429, Hôpital Necker-Enfants Malades, Paris, France
Unité de réanimation pédiatrique, Hôpital Kremlin-Bicêtre, Le Kremlin Bicêtre, France
^|||| Laboratoire de Génétique Humaine des Maladies Infectieuses, Université René Descartes-INSERM U550, Faculté de Médecine Necker-Enfants Malades, Paris, France
^¶¶ Unité de Biologie Moléculaire de l’Expression Génique URA CNRS 1773, Institut Pasteur, Paris, France

, or (C.B.) Service de Dermatologie, Hôpital Necker Enfants malades, 149 rue de Sèvres 75015, Paris, France, EU. E-mail: christine.bodemer{at}nck.ap-hop-paris.fr

--> 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-B 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-B essential modulator, with a genotype-phenotype correlation in hemizygous males. In contrast, loss-of-function mutations and hypomorphic mutations may cause IP in females.

Key Words: children • osteopetrosis • lymphedema • anhidrotic ectodermal dysplasia • incontinentia pigmenti • immunodeficiency • bone marrow transplantation

Abbreviations: IP, incontinentia pigmenti • NEMO, NF-B essential modulator • OL-EDA-ID, osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency • SD, standard deviation • Ig, immunoglobulin • IL, interleukin • TNF-, tumor necrosis factor- • HSCT, hematopoietic stem cell transplantation

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Received for publication Oct 31, 2001; Accepted Feb 13, 2002.

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