This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dupuis-Girod, S. Articles by Bodemer, C. Search for Related Content PubMed PubMed Citation Articles by Dupuis-Girod, S. Articles by Bodemer, C. Related Collections Related AAP Red Book topics: Diseases Caused by Nontuberculous... Salmonella Infections Social Bookmarking                         What's this?

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

---

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

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Luengo-Blanco, C. Prando, J. Bustamante, W. C. Aragao-Filho, P. V. S. Pereira, J. Rehder, C. Padden, J.-L. Casanova, P. E. Newburger, and A. Condino-Neto Essential role of nuclear factor-{kappa}B for NADPH oxidase activity in normal and anhidrotic ectodermal dysplasia leukocytes Blood, August 15, 2008; 112(4): 1453 - 1460. [Abstract] [Full Text] [PDF]

				A. J. Mancini, L. P. Lawley, and G. Uzel X-Linked Ectodermal Dysplasia With Immunodeficiency Caused by NEMO Mutation: Early Recognition and Diagnosis Arch Dermatol, March 1, 2008; 144(3): 342 - 346. [Abstract] [Full Text] [PDF]

				O. Filipe-Santos, J. Bustamante, M. H. Haverkamp, E. Vinolo, C.-L. Ku, A. Puel, D. M. Frucht, K. Christel, H. von Bernuth, E. Jouanguy, et al. X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production J. Exp. Med., July 10, 2006; 203(7): 1745 - 1759. [Abstract] [Full Text] [PDF]

				A. Morlon, A. Munnich, and A. Smahi TAB2, TRAF6 and TAK1 are involved in NF-{kappa}B activation induced by the TNF-receptor, Edar and its adaptator Edaradd Hum. Mol. Genet., December 1, 2005; 14(23): 3751 - 3757. [Abstract] [Full Text] [PDF]

				A. Puel, Kun Yang, C.-L. Ku, H. von Bernuth, J. Bustamante, O. F. Santos, T. Lawrence, H.-H. Chang, H. Al-Mousa, C. Picard, et al. Heritable defects of the human TLR signalling pathways Innate Immunity, August 1, 2005; 11(4): 220 - 224. [Abstract] [PDF]

				J.-C. Tille and M.S. Pepper Hereditary Vascular Anomalies: New Insights Into Their Pathogenesis Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1578 - 1590. [Abstract] [Full Text] [PDF]

				R. Nishikomori, H. Akutagawa, K. Maruyama, M. Nakata-Hizume, K. Ohmori, K. Mizuno, A. Yachie, T. Yasumi, T. Kusunoki, T. Heike, et al. X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival Blood, June 15, 2004; 103(12): 4565 - 4572. [Abstract] [Full Text] [PDF]

				T. Andrews and K. E. Sullivan Infections in Patients with Inherited Defects in Phagocytic Function Clin. Microbiol. Rev., October 1, 2003; 16(4): 597 - 621. [Abstract] [Full Text] [PDF]

				E D Carrol, A R Gennery, T J Flood, G P Spickett, and M Abinun Anhidrotic ectodermal dysplasia and immunodeficiency: the role of NEMO Arch. Dis. Child., April 1, 2003; 88(4): 340 - 341. [Abstract] [Full Text] [PDF]

				A. Smahi, G. Courtois, S. H. Rabia, R. Doffinger, C. Bodemer, A. Munnich, J.-L. Casanova, and A. Israel The NF-{kappa}B signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromes Hum. Mol. Genet., October 1, 2002; 11(20): 2371 - 2375. [Abstract] [Full Text] [PDF]