Lymphedema People Logo



Lymphedema Osteopetrosis Ectodermal 

Synonyms:

Heredity: 

Diagnosis: 

Symptoms:

Complications:

Treatment:

Pat O'Connor

June 8, 2008

------------------------

A novel NEMO gene mutation causing osteopetrosis, lymphoedema, hypohidrotic ectodermal dysplasia and immunodeficiency (OL-HED-ID).

Nov 2011

Roberts CM, Angus JE, Leach IH, McDermott EM, Walker DA, Ravenscroft JC.

Source

Department of Dermatology, Nottingham University Hospitals, Nottingham, UK. catherine.roberts@nuh.nhs.uk

Abstract

Genetic conditions are increasingly recognised as a cause of multisystem diseases in children. We report a 6-year-old boy with hypohidrotic ectodermal dysplasia, immunodeficiency, osteopetrosis and lymphoedema, associated with a novel mutation in the NF-κβ essential modulator (NEMO) gene. He is the longest surviving of three reported boys with these clinical features. Hypohidrotic ectodermal dysplasia, a congenital disorder of teeth, hair and eccrine sweat glands is most commonly inherited as an X-linked recessive trait. Associated immunodeficiency (HED-ID) may give rise to serious infections in early life. Mutations in the NEMO gene give rise to a heterogeneous group of disorders, including the X-linked dominant disorder incontinentia pigmenti. This is characterised by typical skin changes leading to linear pigmentary change and variable associated features; in males, prenatal death usually occurs. Our patient, like one if the previous cases and all of their mothers, demonstrates features of incontinentia pigmenti. 

SpringerLink

http://www.springerlink.com/content/lx24u314n7748164/

------------------------

#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 http://omim.org/entry/300301

------------------------

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:

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

=================

External Links:

===

Ectodermal dysplasia with immunodeficiency and lymphedema, but not osteopetrosis, is
associated with a unique NF-kB Essential Modulator (NEMO) mutation.

http://www.clinimmsoc.org/non-cms-pages/meetings/satellites/2005/pid/risma.pdf

....

Ectodermal dysplasia - Medline Plus

....

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

....

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

....

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

....

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

....

Anhidrotic ectodermal dysplasia - immunodeficiency - osteopetrosis - lymphedema 

OrphaNet

http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=69088

=================

Support Groups:

===

Ectodermal Dysplasia Society (1) United Kingdom

National Foundation for Ectodermal Dysplasias United States

Lymphedema People for secondary complication of Lymphedema

OrphaNet List

http://www.orpha.net/consor/cgi-bin/SupportGroup_Search_Simple.php?lng=EN&LnkId=10922&Typ=Pat

=================

Classification and External Resources:

===

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

==============

Join us as we work for lymphedema patients everywhere:

Advocates for Lymphedema

Dedicated to be an advocacy group for lymphedema patients. Working towards education, legal reform, changing insurance practices, promoting research, reaching for a cure.

http://health.groups.yahoo.com/group/AdvocatesforLymphedema/

Subscribe: AdvocatesforLymphedema-subscribe@yahoogroups.com

Pat O'Connor

Lymphedema People / Advocates for Lymphedema

===========================

For information about Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema\

For Information about Lymphedema Complications

http://www.lymphedemapeople.com/wiki/doku.php?id=complications_of_lymphedema

For Lymphedema Personal Stories

http://www.lymphedemapeople.com/phpBB3/viewforum.php?f=3

For information about How to Treat a Lymphedema Wound

http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound

For information about Lymphedema Treatment 

http://www.lymphedemapeople.com/wiki/doku.php?id=treatment

For information about Exercises for Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema

For information on Infections Associated with Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema

For information on Lymphedema in Children

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children

Lymphedema Glossary

http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing

===========================

Lymphedema People - Support Groups

-----------------------------------------------

Children with Lymphedema

The time has come for families, parents, caregivers to have a support group of their own. Support group for parents, families and caregivers of chilren with lymphedema. Sharing information on coping, diagnosis, treatment and prognosis. Sponsored by Lymphedema People.

http://health.groups.yahoo.com/group/childrenwithlymphedema/

Subscribe: childrenwithlymphedema-subscribe@yahoogroups.com

......................

Lipedema Lipodema Lipoedema

No matter how you spell it, this is another very little understood and totally frustrating conditions out there. This will be a support group for those suffering with lipedema/lipodema. A place for information, sharing experiences, exploring treatment options and coping.

Come join, be a part of the family!

http://health.groups.yahoo.com/group/lipedema_lipodema_lipoedema/?yguid=209645515

Subscribe: lipedema_lipodema_lipoedema-subscribe@yahoogroups.com

......................

MEN WITH LYMPHEDEMA

If you are a man with lymphedema; a man with a loved one with lymphedema who you are trying to help and understand come join us and discover what it is to be the master instead of the sufferer of lymphedema.

http://health.groups.yahoo.com/group/menwithlymphedema/

Subscribe: menwithlymphedema-subscribe@yahoogroups.com

......................

All About Lymphangiectasia

Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.

http://health.groups.yahoo.com/group/allaboutlymphangiectasia/

Subscribe: allaboutlymphangiectasia-subscribe@yahoogroups.com

......................

Lymphatic Disorders Support Group @ Yahoo Groups

While we have a number of support groups for lymphedema... there is nothing out there for other lymphatic disorders. Because we have one of the most comprehensive information sites on all lymphatic disorders, I thought perhaps, it is time that one be offered.

DISCRIPTION

Information and support for rare and unusual disorders affecting the lymph system. Includes lymphangiomas, lymphatic malformations, telangiectasia, hennekam's syndrome, distichiasis, Figueroa
syndrome, ptosis syndrome, plus many more. Extensive database of information available through sister site Lymphedema People.

http://health.groups.yahoo.com/group/lymphaticdisorders/

Subscribe: lymphaticdisorders-subscribe@yahoogroups.com

.

==========================

Lymphedema People New Wiki Pages

Have you seen our new “Wiki” pages yet?  Listed below are just a sample of the more than 140 pages now listed in our Wiki section. We are also working on hundred more.  Come and take a stroll! 

Lymphedema Glossary 

http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing 

Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema 

Arm Lymphedema  

http://www.lymphedemapeople.com/wiki/doku.php?id=arm_lymphedema 

Leg Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=leg_lymphedema 

Acute Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=acute_lymphedema 

The Lymphedema Diet 

http://www.lymphedemapeople.com/wiki/doku.php?id=the_lymphedema_diet 

Exercises for Lymphedema  

http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema 

Diuretics are not for Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=diuretics_are_not_for_lymphedema 

Lymphedema People Online Support Groups 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_people_online_support_groups 

Lipedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=lipedema 

Treatment 

http://www.lymphedemapeople.com/wiki/doku.php?id=treatment 

Lymphedema and Pain Management 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pain_management 

Manual Lymphatic Drainage (MLD) and Complex Decongestive Therapy (CDT)

http://www.lymphedemapeople.com/wiki/doku.php?id=manual_lymphatic_drainage_mld_complex_decongestive_therapy_cdt 

Infections Associated with Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema 

How to Treat a Lymphedema Wound 

http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound 

Fungal Infections Associated with Lymphe dema 

http://www.lymphedemapeople.com/wiki/doku.php?id=fungal_infections_associated_with_lymphedema 

Lymphedema in Children 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children 

Lymphoscintigraphy 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphoscintigraphy 

Magnetic Resonance Imaging 

http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging 

Extraperitoneal para-aortic lymph node dissection (EPLND) 

http://www.lymphedemapeople.com/wiki/doku.php?id=extraperitoneal_para-aortic_lymph_node_dissection_eplnd 

Axillary node biopsy 

http://www.lymphedemapeople.com/wiki/doku.php?id=axillary_node_biopsy

Sentinel Node Biopsy 

http://www.lymphedemapeople.com/wiki/doku.php?id=sentinel_node_biopsy

Small Needle Biopsy - Fine Needle Aspiration 

http://www.lymphedemapeople.com/wiki/doku.php?id=small_needle_biopsy 

Magnetic Resonance Imaging 

http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging 

Lymphedema Gene FOXC2

 http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_foxc2

 Lymphedema Gene VEGFC

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_vegfc

 Lymphedema Gene SOX18

 http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_sox18

 Lymphedema and Pregnancy

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pregnancy

Home page: Lymphedema People

http://www.lymphedemapeople.com

Page Updated: Jan. 9, 2012