Lymphedema Osteopetrosis Ectodermal

Synonyms:

Ectodermal Dysplasia, Anhidrotic, with immunodeficiency, osteopetrosis, and lymphedema.

Heredity:

Gene map locus Xq28; hypomorphic mutations in NEMO (IKBKG; 300248).

Diagnosis:

Family history and physical examination would be the central diagnostic tools. Lymphatic dysplasia could be verified through the use of a lymphoscintigraphy test. Blood tests to identify immunodeficiency.

Symptoms:

Osteopetrosis, immunodeficiency, sparse hair, facial dysmorphy, delayed eruption of teeth, and sweat gland abnormalities.

Complications:

Lymphedema - Infections such as cellulitis, lymphangitis, erysipelas, Draining wounds that leak lymphorrea, Loss of Function due to the swelling and limb changes, psychological, Deep venous thrombosis, Sepsis, Gangrene, Possible amputation of the limb, Pleural effusions, dry skin, splitting, plaques and nodules, susceptibility to fungus and bacterial infections, chronic localized inflammations, lymphatic cancers, pain, skin complications, debilitating joint problems.

Treatment:

Treatment would include correction of impaired vision, special education for the retardation.
The lymphedema treatment program would include: Manual lymphatic drainage; compression wraps or compression bandages (using short stretch bandages), compression garments, compression sleeves.

Pat O'Connor

June 8, 2008

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#300301	Links
ECTODERMAL DYSPLASIA, ANHIDROTIC, WITH IMMUNODEFICIENCY, OSTEOPETROSIS, AND LYMPHEDEMA; OLEDAID

Gene map locus Xq28

TEXT

A number sign (#) is used with this entry because the phenotype is caused by hypomorphic mutations in NEMO (IKBKG; 300248).

Doffinger et al. (2001) examined 2 unrelated male patients who presented with the novel OL-EDA-ID syndrome. Both were sons of mothers with mild incontinentia pigmenti (308300), and both died of overwhelming multiple infections at 2.5 and 1.5 years of age, respectively. Both had osteopetrosis, lymphedema, and anhidrotic ectodermal dysplasia. Immunologic variables in the second patient showed a poor inflammatory response and increases in the levels of blood inflammatory markers with fever either absent or delayed during infection. Blood monocytes and polymorphonuclear cells were normal in number and morphology. The B- and T-cell counts and responses to vaccine protein antigens were normal. Serum titers of antibodies against S. pneumoniae were low, despite proven infection. Serum titers of isohemagglutinins were low. Serum levels of immunoglobulin isotypes were normal for age, with the exception of low to normal IgG levels. Both patients carried an X420W mutation in IKBKG, or NEMO (300248.0002). Different alleles were present at the flanking polymorphic loci in the 2 patients, indicating 2 independent mutational events. Both patients died of overwhelming infectious disease caused by a variety of microorganisms, including gram-positive cocci, gram-negative bacilli, mycobacteria, and fungi. There were impaired cellular responses to TNF-alpha (191160). Doffinger et al. (2001) compared the induction of IFN-gamma (147570) by peripheral blood mononuclear cells (PBMC) from one of the patients and a control. The patient's PBMC displayed a lower level of IFN-gamma production upon costimulation with IL12 (see 161560) and various concentrations of IL1-beta (147720) or IL18 (600953) than the control PBMC. There were impaired cellular responses to lipopolysaccharide in this patient. The patient also exhibited dissociated cellular responses to CD154 (CD40LG; 300386), suggesting that some but not all CD40 (109535)-mediated signals are NEMO-dependent in both dentritic cells and B cells.

REFERENCES

1. Doffinger, R.; Smahi, A.; Bessia, C.; Geissmann, F.; Feinberg, J.; Durandy, A.; Bodemer, C.; Kenwrick, S.; Dupuis-Girod, S.; Blanche, S.; Wood, P.; Rabia, S. H.; and 16 others :: X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappa-B signaling. Nature Genet. 27: 277-285, 2001.
PubMed ID : 11242109

CREATION DATE

Ada Hamosh : 3/2/2001

EDIT HISTORY

carol : 4/8/2002
terry : 11/14/2001
alopez : 4/26/2001
alopez : 4/24/2001
alopez : 3/5/2001
alopez : 3/2/2001

OMIM

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Lymphedema Osteopetrosis Ectodermal

Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother.

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.

Unite d'Immunologie et d'He matologie pediatriques, Hopital Necker-Enfants Malades, Paris, France.

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.

Publication Types:

Case Reports

PMID: 12042591 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12042591&dopt=Abstract

Full Article

http://pediatrics.aappublications.org/cgi/content/full/109/6/e97

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External Links:

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Ectodermal dysplasia - Medline Plus

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Ectodermal Dysplasia - eMedicine

X-Linked Ectodermal Dysplasia and Immunodeficiency Cause by Reversion Mosaicism of NEMO Reveals a Critical Role for NEMO in Human T-cell Deveopment and/or Survival.

Jan 2004

Blood Journal

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Anhidrotic ectodermal dysplasia and immunodeficiency: the role of NEMO - April 2003

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Successful allogeneic hemopoietic stem cell transplantation in a child who had anhidrotic ectodermal dysplasia with immunodeficiency. - July 2006

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A point mutation in NEMO associated with anhidrotic ectodermal dysplasia with immunodeficiency pathology results in destabilization of the oligomer and reduces lipopolysaccharide- and tumor necrosis factor-mediated NF-kappa B activation. - March 2006

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Support Groups:

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Ectodermal Dysplasia Society (1) United Kingdom

National Foundation for Ectodermal Dysplasias United States

Lymphedema People for secondary complication of Lymphedema

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Classification and External Resources:

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ICD-10

Q82.4		Ectodermal dysplasia (anhidrotic)
		Excludes:	Ellis-van Creveld syndrome ( Q77.6 )

ICD-9

2008 ICD-9-CM Diagnosis 757.31

Congenital ectodermal dysplasia

A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, FOCAL DERMAL HYPOPLASIA, and aplasia cutis congenita.

757.31 is a specific code that can be used to specify a diagnosis
757.31 contains 13 index entries
View the ICD-9-CM Volume 1 757.* hierarchy

Index entries containing 757.31:

Basan's (hidrotic) ectodermal dysplasia 757.31
Bason's (hidrotic) ectodermal dysplasia 757.31
Clouston's (hidrotic) ectodermal dysplasia 757.31
Dysplasia - see also Anomaly

ectodermal (anhidrotic) (Bason) (Clouston's) (congenital) (Feinmesser) (hereditary) (hidrotic) (Marshall) (Robinson's) 757.31
hypohidrotic ectodermal 757.31

Ectodermal dysplasia, congenital 757.31
Feinmesser's (hidrotic) ectodermal dysplasia 757.31
Hypohidrotic ectodermal dysplasia 757.31
Marshall's (hidrotic) ectodermal dysplasia 757.31
Robinson's (hidrotic) ectodermal dysplasia 757.31
Siemens' syndrome

ectodermal dysplasia 757.31

Syndrome - see also Disease

Clouston's (hidrotic ectodermal dysplasia) 757.31
Siemens'
- ectodermal dysplasia 757.31

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Information and support for rare and unusual disorders affecting the lymph system. Includes lymphangiomas, lymphatic malformations, telangiectasia, hennekam's syndrome, distichiasis, Figueroa
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