Hay-Wells Syndrome

Hay-Wells Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Hay-Wells Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • AEC Syndrome
  • Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate
  • Hay-Wells Syndrome of Ectodermal Dysplasia

Disorder Subdivisions

  • None

General Discussion

Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome, is a rare inherited disorder that belongs to a group of disorders known as the ectodermal dysplasias. Major characteristics of Hay-Wells syndrome include sparse, coarse, wiry hair; small, sparse eyelashes; excess bands of fibrous tissue that cause the edges (margins) of the upper and lower eyelids to fuse together (ankyloblepharon filiforme adnatum); cleft palate; and less often cleft lip. Hay-Wells syndrome is inherited as an autosomal dominant trait.



The ectodermal dysplasias are a group of more than 150 related disorders that result from abnormalities during early embryonic development. Ectodermal dysplasias typically affect the hair, teeth, nails, and/or skin. The ectodermal dysplasias are inherited disorders, but the pattern of inheritance is varied.

Symptoms

The symptoms of Hay-Wells syndrome may vary from case to case. The face and head (craniofacial region), skin, nails, and additional areas of the body may be affected.



Infants with Hay-Wells syndrome may have certain characteristic symptoms that are present at birth (congenital) including excess bands of fibrous tissue that causes the edges (margins) of the upper and lower eyelids to fuse together (ankyloblepharon filiforme adnatum); incomplete closure of the roof of the mouth (cleft palate); and, less often, an abnormal groove in the upper lip (cleft lip).



Additional craniofacial features associated with Hay-Wells syndrome include an underdeveloped upper jawbone (maxillary hypoplasia); a broad nasal bridge; an oval-shaped face; sparse, wiry hair; sparse or absent eyelashes; and a variety of dental abnormalities. Such abnormalities may include widely-spaced teeth, underdeveloped teeth (hypodontia), missing teeth (partial anodontia), and abnormally pointed (conical) teeth.



Some infants with Hay-Wells syndrome may exhibit skin fragility with patches of eroded skin. Eroded skin may be apparent at birth. The amount of skin affected varies widely from case to case. Affected infants may also experience repeated scalp infections (dermatitis) eventually resulting in patches of hair loss (alopecia) and scarring. Some infants may have an impaired ability to sweat (hypohidrosis) resulting in heat intolerance. Additional skin symptoms include abnormally thick, rough skin on the palms of the hands and the soles of the feet (palmoplantar keratoderma) and patches of discolored skin due to excess pigment (hyperpigmentation).



Additional findings associated with Hay-Wells syndrome may include malformed (dystrophic) nails, low-set cup-shaped ears, and absence of one or more of the upper or lower duct openings of the eyes (lacrimal puncta). Inadequate tearing (lacrimation) may lead to abnormal sensitivity to light (photophobia).



In some cases, repeated middle ear infections (otitis media) and conducive hearing loss may occur. Some individuals may develop velopharyngeal incompetence, a birth defect in the opening structure of the throat. In this condition, the part of the mouth under the nasal passages is not completely closed. This condition may cause food to spit up through the nose and a speech impairment. In some cases velopharyngeal incompetence may occur instead of cleft lip and/or palate.



Uncommon findings sometimes associated with Hay-Wells syndrome include extra (supranumerary) nipples, abnormal placement of the urinary opening (meatus) on the underside of the penis (hypospadias), heart abnormalities, and webbing of the toes (syndactyly).

Causes

Most cases of Hay-Wells syndrome occur randomly as the result of a spontaneous (de novo) genetic change (i.e., new mutation). This mutation is then inherited as an autosomal dominant trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.



Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.



Investigators have determined that Hay-Wells syndrome may be caused by disruption or changes (mutations) of the p63 gene located on the long arm of (q) of chromosome 3 (3q27).



Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 3q27" refers to band 27 on the long arm of chromosome 3. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Affected Populations

Hay-Wells syndrome affects males and females in equal numbers. The incidence of Hay-Wells syndrome is unknown. The disorder was first identified in the medical literature in 1976.

Standard Therapies

Diagnosis

The diagnosis of Hay-Wells syndrome may be suspected by a thorough clinical evaluation, a detailed patient history and identification of characteristic symptoms. Molecular genetic testing may be used to identify mutations of the p63 gene in some cases.



Treatment

The treatment of Hay-Wells syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, physicians who specialize in the diagnosis and treatment of disorders of the skin (dermatologists), specialists who assess and treat hearing problems (audiologists); dental specialists, eye specialists (ophthalmologists), and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.



Infants with skin erosions may be treated by skin softening (emollient) ointments, antibiotics, drugs that are applied directly to the skin because they help prevent infection (antiseptics), and protective skin dressings. Partial fusion of eyelids (ankyloblepharon) may resolve without treatment (spontaneously) or may require surgery.



In some cases, reconstructive surgery may be beneficial for individuals with cleft palate and/or cleft lip. Dental surgery and/or corrective devices may be employed to treat misshapen teeth and, if teeth are missing, dentures may be appropriate. Affected individuals should also pay particular attention to the prevention of tooth decay. In addition, in some cases, speech therapy may also be helpful. Heat and excess exercise should be avoided.



Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



The palate of cleft palate patients is closed during early childhood but difficulties may persist if the palate is excessively short in relation to the pharynx. Researchers are studying a teflon-glycerine paste that is applied to the rear of the pharynx in a minor surgical procedure. A rounder bump or ledge is formed, bringing the pharynx and palate into the proper relationship with each other. The hardened paste remains in place indefinitely; no side effects have been observed. Children as young as eight years old have been treated with this procedure. For further information on this procedure for cleft palate contact:



William N. Williams, D.D.S.

University of Florida

College of Dentistry

Box J-424

Gainsville, FL 32610

(904) 392-4370



The National Foundation for Ectodermal Dysplasias (NFED) and the School of Dental Medicine (SDM) at Southern Illinois University are engaged in a program to provide dental implants to individuals affected by ectodermal dysplasia. Interested individuals should contact NFED for the initial screening of potential participants. Such individuals must have ectodermal dysplasia, be missing a majority of teeth in the lower jaw (mandible), and not have any complicating factors. In addition, they must be willing to participate in the related research project, which requires periodic check-ups. For more information, please contact the National Foundation for Ectodermal Dysplasias, which is listed in the Resources section below.

References

TEXTBOOKS

McGrath JA, Irvine AD. Hay-Wells Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:116-7.



Jones KL., ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:296.



Champion RH, et al., eds. Textbook of Dermatology. 5th ed. Cambridge, MA: Blackwell Scientific Publications; 1992:338.



Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:720.



Buyce ML., ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:599-600.



JOURNAL ARTICLES

Chan I, McGrath JA, KivirikkoS. Rapp-Hodgkin syndrome and the tail of p63. Clin Exp Dermatol. 2005;30:183-6.



Fomenkov A, Huang YP, Topaloglu O, et al., P63 alpha mutations lead to aberrant splicing of keratinocyte growth factor receptor in the Hay-Wells syndrome. J Biol Chem. 2003;278:23906-14.



Westfall MD, Mays DJ, Sniezek JC, Pietenpol JA. The Delta Np63 alpha phophoprotein binds the p21 and 14-3-3 sigma promoters in vivo and has transcriptional repressor activity that is reduced by Hay-Wells syndrome-derived mutations. Mol Cell Biol. 2003;23:2264-76.



McGrath JA, Duijf PHG, Doetsch V, et al., Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63. Hum Mol Genet. 2001;10:221-229.



Vanderhooft SL, Stephan MJ, Sybert VP. Severe skin erosions and scalp infections in AEC syndrome. Pediatr Dermatol. 1993;10:334-40.



Fosko SW, Stenn KS, Bolognia JL. Ectodermal dysplasias associated with clefting: significance of scalp dermatitis. J Am Acad Dermatol. 1992;27:249-56.



FROM THE INTERNET

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:106260; Last Update:4/26/2001. Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=106260 Accessed on: 3/1/2005.



Friday KE. Ectodermal Dysplasias. Emedicine. 2004. Available at: http://www.emedicine.com/derm/topic114.htm Accessed on: 3/1/2005.

Resources

National Foundation for Ectodermal Dysplasias

6 Execuitive Drive

Suite 2

Fairview Hiights, IL 62208

Tel: (618)566-2020

Fax: (618)566-4718

Email: info@nfed.org

Internet: http://www.nfed.org



March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



Cleft Palate Foundation

1504 East Franklin Street

Suite 102

Chapel Hill, NC 27514-2820

USA

Tel: (919)933-9044

Fax: (919)933-9604

Tel: (800)242-5338

Email: info@cleftline.org

Internet: http://www.cleftline.org



NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Information Clearinghouse

One AMS Circle

Bethesda, MD 20892-3675

USA

Tel: (301)495-4484

Fax: (301)718-6366

Tel: (877)226-4267

TDD: (301)565-2966

Email: NIAMSinfo@mail.nih.gov

Internet: http://www.niams.nih.gov/



NIH/National Institute of Dental and Craniofacial Research

Building 31, Room 2C39

31 Center Drive, MSC 2290

Bethesda, MD 20892

USA

Tel: (301)496-4261

Fax: (301)480-4098

Tel: (866)232-4528

Email: nidcrinfo@mail.nih.gov

Internet: http://www.nidcr.nih.gov/



Craniofacial Foundation of America

975 East Third Street

Chattanooga, TN 37403

Tel: (423)778-9176

Fax: (423)778-8172

Tel: (800)418-3223

Email: terry.smyth@erlanger.org

Internet: http://www.craniofacialfoundation.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Ectodermal Dysplasia Society

Unit 1 Maida Vale Business Centre

Leckhampton

Cheltenham

Gloucestershire

England, GL53 7ER

United Kingdom

Tel: 4401242261332

Tel: 4407805775703

Email: diana@ectodermaldysplasia.org

Internet: http://www.ectodermaldysplasia.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.