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Hay-Wells Syndrome
Synonyms of Hay-Wells Syndrome
- AEC Syndrome
- Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate
- Hay-Wells Syndrome of Ectodermal Dysplasia
Disorder Subdivisions
- No subdivisions found.
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.
Related Disorders
Symptoms of the following disorders can be similar to those of Hay-Wells syndrome. Comparisons may be useful for a differential diagnosis:
Rapp-Hodgkin syndrome, an extremely rare inherited multisystem disorder that is apparent at birth (congenital) or during infancy, belongs to a group of diseases known as ectodermal dysplasias. Ectodermal dysplasias typically affect the skin, teeth, hair, and/or nails. Rapp-Hodgkin syndrome is characterized by a reduced ability to sweat (hypohidrosis); an incomplete closure of the roof of the mouth (cleft palate) and/or an abnormal groove in the upper lip (cleft lip); partial or complete absence (hypodontia or partial anodontia) and/or abnormal smallness (microdontia) of primary and secondary (permanent) teeth. Infants and children with the disorder also have abnormally sparse, coarse, wiry scalp hair that is often lost prematurely during adulthood (alopecia); unusually slow-growing, improperly developed nails (dysplastic); and, in some cases, additional physical abnormalities. In most cases, Rapp-Hodgkin syndrome is inherited as an autosomal dominant trait. Rapp-Hodgkin syndrome and Hay-Wells syndrome are caused by different mutations of the same gene (allelic disorders) leading some researchers to believe that the two disorders represent one clinical entity. (For more information on this disorder, choose "Rapp-Hodgkin" as your search term in the Rare Disease Database.)
Epidermolysis bullosa (EB) refers to a group of rare, inherited skin disorders characterized by fragile skin, painful blistering, and small fluid-filled lesions that develop following minor trauma to the skin. The mucous membranes are also involved in some forms of EB. Healing may be slow and blisters may leave multiple scars and/or damage the underlying muscle tissue. Some severe forms may involve the eyes, tongue, and esophagus, and some may produce scarring and disabling musculoskeletal deformities. There are three major forms: epidermolysis bullosa simplex (EB simplex), the most common; dystrophic epidermolysis bullosa (DEB), and junctional epidermolysis bullosa (JEB). (For more information on these disorders, choose "Epidermolysis Bullosa" as your search term in the Rare Disease Database.)
CHANDS, which stands for curly hair-ankyloblepharon-nail dysplasia syndrome, is a rare inherited disorder. CHANDS is one of a group of disorders known as ectodermal dysplasias. Affected infants have curly hair, excess bands of fibrous tissue that cause the edges (margins) of the upper and lower eyelids to fuse together (ankyloblepharon), and malformed (dysplastic) nails. Additional symptoms include lip pits. CHANDS is inherited as an autosomal recessive trait.
Popliteal pterygium syndrome is a rare inherited disorder characterized by cleft lip and/or cleft palate, lower lip pits, webbed skin (pterygium) on the backs of both legs (popliteal) and between the legs (intercrural), malformation and/or underdevelopment of the genitals, webbing or fusion of the fingers and/or toes (syndactyly), adhesion of upper and lower jaw and adhesion of upper and lower eyelids (ankyloblepharon). A cone-shaped fold of skin on the nail of the big toe is a very distinctive finding in this condition. Popliteal pterygium syndrome is at the severe end of the spectrum of disorders caused by abnormalities in the interferon regulatory factor (IRF6) gene. Popliteal pterygium syndrome is inherited as an autosomal dominant trait. (For more information about this disorder, choose "IRF6-related disorders" as your search term in the Rare Disease Database.)
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.
Organizations related to Hay-Wells Syndrome
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder (e.g., cleft palate, etc.)
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.
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Report last updated: 2008/05/25 00:00:00 GMT+0
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