Rapp Hodgkin Syndrome
NORD is very grateful to Betsy Ferguson, PhD, of the Oregon Health Sciences University for assistance in the preparation of this report.
Synonyms of Rapp Hodgkin Syndrome
- Ectodermal dysplasia, anhidrotic, with cleft lip and cleft palate
- Ectodermal dysplasia, Rapp-Hodgkin type
- Rapp-Hodgkin (hypohidrotic) ectodermal dysplasia syndrome
- No subdivisions found.
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.
The symptoms and physical findings associated with Rapp-Hodgkin syndrome vary greatly from case to case.
Rapp-Hodgkin syndrome is characterized by an impaired ability or lack of ability to sweat (hypohidrosis or anhidrosis) due to a reduced number of sweat glands and/or pores in the skin. However, in some cases, affected individuals may sweat profusely on the scalp. Individuals with Rapp-Hodgkin syndrome may be susceptible to abnormally high body temperatures (hyperthermia) particularly during childhood due to impaired ability to sweat.
In most cases, infants with Rapp-Hodgkin syndrome may have incomplete closure of the roof of the mouth (cleft palate) and/or a groove in the upper lip (cleft lip). In addition, affected infants and children may be missing some or all primary (deciduous) and permanent (secondary) teeth (hypodontia or oligodentia). Existing teeth may be small, cone-shaped (conical), and/or prone to decay (caries). In addition, affected individuals may have an abnormally high forehead, underdevelopment of the middle portion of the face (midface hypoplasia), a low nasal bridge, and/or a narrow nose with underdeveloped outer corners of the nostrils (alae nasi). In some cases, the soft-tissue structure that hangs at the back of the throat (uvula) may be abnormally divided (bifid), the mouth may be abnormally small, and/or the upper jawbone may be underdeveloped (maxillary hypoplasia). Infants with this disorder often experience a condition in which the soft, back portion of the roof of the mouth (soft palate) does not adequately press against the back wall of the throat (pharynx) during swallowing (velopharyngeal incompetency), thus potentially failing in its function to prevent food from entering the nasal passage. In some cases, feeding and/or speech difficulties may result from these abnormalities. In addition, lack of a sufficient mucous coating on the vocal cords may contribute to speaking difficulties and can affect vocal quality.
Most infants with Rapp-Hodgkin syndrome have characteristic abnormalities affecting the hair. The scalp hair, which is often a blond or straw-like color, may be unusually sparse, dry, and/or coarse. Hair may grow slowly, appear flattened and twisted (pili torti), and be difficult to comb. Later in life, affected individuals may develop areas of patchy baldness (alopecia) at the back of the head (occiput). In some cases, scars or ulcer-like lesions may form on the scalp. In adults, premature baldness may affect both males and females. In addition, affected individuals may also have abnormally thin eyebrows and eyelashes and/or small, misshapen slow-growing fingernails and toenails (nail dysplasia).
In some cases, infants with Rapp-Hodgkin syndrome may develop frequent (recurrent) or prolonged (chronic) inflammation of the middle ear (otitis media), possibly due, in part, to cleft palate. In addition, affected infants may be born with ear canals that extremely narrow (e.g., slit-like) or closed (atretic). Affected individuals may experience hearing impairment of one or both ears.
Individuals with Rapp-Hodgkin syndrome may also have eye (ocular) abnormalities. The small openings in the inner corners of the eyelids where tears normally drain may be absent or fail to develop (lacrimal puncta agenesis or aplasia), as may the canals (lacrimal canaliculi or tear ducts) that carry tears from their site of origin (lacrimal glands) to the eyes. In some cases, aplasia of the lacrimal canaliculi may cause a sudden overflow of tears (epiphora). In addition, affected individuals may have droopy upper eyelids (ptosis) or be abnormally sensitive to light (photophobia). In some cases, the transparent, thin membrane that protects and helps lubricate the eyelids and whites of the eyes (conjunctiva) may become inflamed and discharge a pus-like fluid (purulent conjunctivitis).
Some males with Rapp-Hodgkin syndrome may exhibit misplacement of the urinary opening, such as on the underside of the penis (hypospadias). In females, there may be abnormalities of the skin folds (labia) of the external portion of female genitalia (vulva). In some cases, additional abnormalities may be present including short stature and/or webbing of two or more fingers and/or toes (syndactyly).
In most cases, Rapp-Hodgkin syndrome is inherited as an autosomal dominant trait. However, X-linked dominant inheritance has not been ruled out. 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 some cases of Rapp-Hodgkin syndrome may be caused by disruption or changes (mutations) of the TP63 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.
Rapp-Hodgkin syndrome is an extremely rare inherited disorder that affects males and females in equal numbers. More than 40 cases have been reported in the medical literature, including several affected individuals within successive generations of certain families (kindreds). In some cases, symptoms and physical features associated with this disorder are apparent at birth (congenital). However, some cases may not become apparent until late infancy.
The exact prevalence of ectodermal dysplasias is unknown. One estimate placed the incidence at 7 infants per 10,000 births.
Most of the ectodermal dysplasias also are characterized by reduced or malformed teeth, hair, and sweat glands, similar to that of Rapp-Hodgkin syndrome. (For more information, choose ectodermal dysplasias as your search term in the Rare Disease Database.) Specific types of ectodermal dysplasias that are most similar to Rapp-Hodgkin syndrome are briefly described below:
Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome (EEC syndrome) is a rare inherited type of ectodermal dysplasia. Symptoms of this disorder may vary from case to case, but the characteristic signs include reduced activity of the sweat glands (hypohidrosis); an underdeveloped upper jaw (maxillary hypoplasia); incomplete closure of the roof of the mouth (cleft palate); a groove in the upper lip (cleft lip); and/or absence of all or part of one or more fingers and/or toes (ectrodactyly). In some cases, affected infants may also have webbing (syndactyly) of the fingers and/or toes. In addition, affected infants may have missing teeth (anodontia); abnormally small teeth (microdontia); malformation (dysplasia) of the nails; and/or sparse, light-colored hair that is wiry and thin. In most cases, affected infants may exhibit abnormalities of the eyes including unusual sensitivity to light (photophobia) and/or abnormalities of the tear (lacrimal) ducts. In some cases, affected individuals may have additional eye abnormalities, hearing impairment, and/or urinary tract abnormalities such as obstruction of the tube that carries urine from the kidney into the bladder (ureter) causing an abnormal accumulation of urine (hydronephrosis) in the pelvis and kidney duct. Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome is inherited as an autosomal dominant trait. While some researchers believe that Rapp-Hodgkin syndrome and ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome are separate disorders, others suspect that they may represent the same disease entity. (For more information on this disorder, choose "Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate" as your search term in the Rare Disease Database.)
Hay-Wells syndrome (AEC syndrome) is a rare inherited form of ectodermal dysplasia. Major characteristics of the disorder include sparse, coarse, and wiry hair; small, sparse eyelashes; excess bands of fibrous tissue that cause the edges (margins) of the upper and lower eyelids to adhere together (ankyloblepharon filiforme adnatum); cleft lip and/or palate; slightly impaired ability to sweat (hypohidrosis); and/or absence of certain teeth (hypodontia). In addition, in some cases, affected infants may have misshapen (dystrophic) nails and/or an underdeveloped upper jawbone (maxillary hypoplasia). Hay-Wells syndrome is inherited as an autosomal dominant trait. Hay-Wells syndrome and Rapp-Hodgkin 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 "Hay Wells" as your search term in the Rare Disease Database.)
Hypohidrotic ectodermal dysplasia (HED) is a rare inherited disorder characterized by a diminished ability to sweat (hypohidrosis) that may result in heat intolerance and recurring fevers. Infants with hypohidrotic ectodermal dysplasia may have abnormally thin, sparse hair (hypotrichosis); and absence of some teeth (hypodontia). Individuals also have characteristic facial abnormalities; dry skin that is soft, thin, and finely wrinkled with diminished coloration (hypopigmentation); and/or wrinkled skin with increased coloration (hyperpigmentation) around the eyes. Other physical findings may include underdeveloped (hypoplastic) or absent mucous glands of the respiratory and gastrointestinal (GI) tracts and an increased tendency to develop allergic disorders such as eczema and asthma. In many cases, additional physical abnormalities may also be present. Mental retardation may be observed in a small percentage of cases, most likely as a consequence of extreme overheating. The range and severity of symptoms and physical characteristics varies from case to case. Hypohidrotic ectodermal dysplasia is usually inherited as an X-linked recessive genetic trait. (For more information on this disorder, choose "Hypohidrotic Ectodermal Dysplasia" as your search term in the Rare Disease Database.)
Rosselli-Gulienetti syndrome is a rare form of ectodermal dysplasia. Major characteristics may include an impaired ability to sweat (hypohidrosis); abnormally small teeth (microdontia); sparse, thin hair (hypotrichosis) over the body; malformation (dysplasia) of the nails; and/or incomplete closure of the roof of the mouth (cleft palate) and/or a groove in the upper lip (cleft lip). In some cases, affected infants may have webbed skin on the backs of both legs (popliteal) and between the fingers and toes (syndactyly). In some cases, additional physical abnormalities may be present. Rosselli-Gulienetti syndrome is thought to be inherited as an autosomal recessive genetic trait.
Rapp-Hodgkin syndrome may be suspected birth based upon a thorough clinical evaluation and identification of characteristic features, such as sparse, coarse hair; impaired ability to sweat (hypohidrosis); and/or cleft lip and/or palate. In most cases, a diagnosis is verified during late infancy when characteristic findings, such as changes in the hair and/or the observation of missing teeth (hypodontia or oligodentia) or abnormally small, misshapen teeth, become more pronounced.
The diagnosis of Rapp-Hodgkin syndrome may be confirmed by a variety of specialized tests. Microscopic examination of small samples of skin tissue (biopsy) may reveal abnormal thinning of the outer layer of the skin (epidermis) and absence of certain specialized structures normally located within the skin (e.g., sweat glands). An examination of hair under a Scanning Electron Microscope (SEM) may demonstrate abnormalities of the hair such as irregular canals running the length of the hair (pili canaliculi) and/or irregular twists. In some cases, pili canaliculi may have two canals (pili bicanaliculi). Examinations of hair using light that sends radiation waves in only one direction (polarizing light studies) may show alternating light and dark bands.
The treatment of Rapp-Hodgkin 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.
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.
In cases where hearing impairment exists, hearing aids may be beneficial. Children with Rapp-Hodgkin syndrome should be monitored closely for signs of hyperthermia, particularly during periods of prolonged activity and/or during the summer months (i.e., high temperatures). Physicians may restrict the use of antihistamines as these drugs may promote further drying of the mucosal covering of the vocal chords.
Genetic counseling will be of benefit for affected individuals and their families. Family members of affected individuals should also receive regular clinical evaluations to detect any symptoms and physical characteristics that may be potentially associated with Rapp-Hodgkin syndrome. Other treatment is symptomatic and supportive.
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
For information about clinical trials sponsored by private sources, contact:
Organizations related to Rapp Hodgkin Syndrome
(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., skin abnormalities, short stature, risk for malignant hyperthermia, etc.].)
Motil KJ. Ectodermal Dysplasia. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:185.
Jones KL., ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:294, 543.
Champion RH, et al., eds. Textbook of Dermatology. 5th ed. Cambridge, MA: Blackwell Scientific Publications; 1992:337.
Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:729-30.
Buyce ML., ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:602-3.
Sahin MT, Turel-Ermertcan A, Chan I, McGrath JA, Ozturkcan S. Ectodermal dysplasia showing clinical overlap between AEC, Rapp-Hodgkin and CHAND syndromes. Clin Exp Dermatol. 2004;29:486-8.
Dianzani I, Garelli E, Gustavsson P, et al., Rapp-Hodgkin and AEC syndromes due to new frameshift mutation in the TP63 gene. J Med Genet. 2003;40:e133.
Plottova-Puech I, Vidal C, Godard W, Cambazard F. Rapp-Hodgkin's syndrome: two cases. Ann Dermatol Venereol. 2003;130:331-6.
Bougeard G, Hadj-Rabia S, Faivre L, Sarafan-Vasseur N, Frebourg T. The Rapp-Hodgkin syndrome results from mutations of TP63 gene. Eur J Hum Genet. 2003;11:700-4.
Moerman P, Fryns JP. Ectodermal dysplasia, Rapp-Hodgkin type in a mother and severe ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC) in her child. Am J Med Genet. 1996;63:479-81.
Rowan DM. Scalp dermatitis, ectodermal dysplasia and cleft lip and palate: rapp-hodgkin or AEC syndrome. Australas J Dermatol. 1996;37:102-3.
Cambiaghi S, Tadini G, Barbareschi M, Menni S, Caputo R. Rapp-Hodgkin syndrome and AEC syndrome: are they the same entity? Br J Dermatol. 1994:130:97-101.
Hart TC, Kyrkanides S. Cephalometric analysis of Rapp-Hodgkin syndrome. J Med Genet. 1994;31:758-60.
Camacho F, Ferrando J, Pichardo AR, Sotillo I, Jorquera E. Rapp-Hodgkin syndrome with pili canaliculi. Pediatr Dermatol. 1993;10:54-7.
O-Donnell BP, James WD. Rapp-Hodgkin ectodermal dysplasia. J Am Acad Dermatol. 1992;27:323-6.
Walpole IR, Goldblatt J. Rapp-Hodgkin hypohidrotic ectodermal dysplasia syndrome. Clin Genet. 1991;39:114-20.
The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.
The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.
Copyright ©1989, 1997, 1998, 1999, 2003
Report last updated: 2008/04/28 00:00:00 GMT+0
NORD's Rare Disease Information Database is copyrighted and may not be published without the written consent of NORD.