Information on the following diseases can be found in the Related Disorders section of this report:

• Ectodermal dysplasias
• Incontinentia pigmenti
• Proteus syndrome

Focal dermal hypoplasia is a rare disorder characterized by skin lesions that look streaked, underdeveloped or "punched-out". Deposits of fat (papillomas) are typically found on the gums, tongue, lips, vulvae and anus. There may be inflammation, itching, reddening, blistering and crusting of the skin. Skin may be absent, discolored or lack pigmentation (color) in some areas. Overgrowth of tissue may be found on the palms of the hands and soles of the feet. Excessive sweating (hyperhidrosis) or absence of sweating (hypohydrosis) is often present on the palms of the hands and soles of the feet. The hair may be sparse, brittle and/or missing.

Eye abnormalities that have been found in some patients with FDH are: drooping eyelids (ptosis); clouding of the cornea; a cleft along the edge of the eyeball (colobmas); involuntary rapid movement of the eye (nystagmus); absence of an eye (anophthalmia); wide spacing between the eyes; more than one color within the iris (heterochromia); dislocation of the lens; crossed eyes (strabismus); and/or exposure of the lining of the eyelid (ectropion).

Patients with FDH may also have a variety of skeletal abnormalities. Curvature of the spine, fused vertebrae, underdeveloped or missing fingers or toes, extra fingers or toes (polydactyly), fingers or toes that have grown together (syndactyly), fingers that bend to the side (clinodactyly), permanently bent fingers (camptodactyly), and/or fusion of bones of the fingers and toes may be present. Other malformations of the skeleton may include a small skull, an underdeveloped jaw, a forward projection of the jaw and/or uneven development of the face, limbs or trunk.

Failure of the teeth to develop properly often occurs in these patients. The teeth may be missing or underdeveloped and are unusually small or improperly spaced. Missing enamel may aid in the development of cavities. Abnormalities of the ears, the eyes, the heart, central nervous system, gastrointestinal system and the kidneys may also be present. Mental retardation can be found in some instances. An extremely wide range of symptoms characterizes FDH, making it difficult to diagnose.

In June 2007, research funded in part by the National Institutes of Health led to the identification of the gene that accounts for most cases of focal dermal hypoplasia. The gene is known as PORCN, and it creates proteins important in the development of the skin, skeleton, and eyes in a developing embryo and fetus. The researchers believe mutations in the PORCN gene cause at least 75 percent of the cases of focal dermal hypoplasia. This research was conducted at the Baylor College of Medicine.

The gene is found on the X chromosome, and the syndrome is believed to be a dominant X-linked trait. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. 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 11p13" refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive.

It is thought that focal dermal hypoplasia when expressed fully is lethal to male fetuses. As a result, of the 200 to 300 cases reported worldwide, only about 10 percent are living males.

Symptoms of the following disorders can be similar to those of focal dermal hypoplasia. Comparisons may be useful for a differential diagnosis:

Ectodermal dysplasias are a group of hereditary, nonprogressive skin diseases in which the affected tissue derives primarily from the ectodermal germ layer. The skin, its derivatives, and some other organs are involved. Symptoms may include eczema, poorly functioning sweat glands, sparse or absent hair, abnormal hair, disfigured nails, and difficulty with the nasal passages and ear canals. (For more information on these disorders, choose "Ectodermal Dysplasias" as your search term in the Rare Disease Database.)

Incontinentia pigmenti (IP) is a rare genetic dermatological disorder affecting the skin, hair, teeth, and central nervous system. It is inherited as an X-linked dominant trait.

IP is characterized by four stages, some of which may overlap. The first stage may be present at birth or appear in early infancy and consists of redness or inflammation of the skin. This irritation includes the scalp as well as the extremities and can last from a few weeks to several months. In the second stage, blisters develop into a raised, wart-like appearance with lesions that look like pustules. The extremities are involved almost exclusively in this stage, which may last for several months but rarely as long as a year. In the third phase, the skin darkens in a swirled pattern sometimes described as a "marble cake" appearance. The fourth stage is called the "atrophic" stage. Pale, hairless patches appear among adolescent and adult patients. The skin changes may fade later in life.

Proteus syndrome is a condition that involves the atypical overgrowth of skin, bones, and the body’s organs. Most medical scientists now agree that Joseph Merrick, known famously as the "Elephant Man", suffered from Proteus syndrome. The overgrowth is progressive and limits the range of motion of affected joints making them massively overgrown and fixed. It usually begins with the fingers, toes and knees but can occur in any part of the body. The spine is commonly affected and the result is scoliosis. Other affected organs include the lungs, spleen, thymus, uterus and colon. Fatty tumors (lipomas) may invade the limbs, trunk and, in some instances, the spinal canal. Other serious complications are blood clots, and some patients have mental retardation. (For more information on this disorder, choose "Proteus syndrome" as your search term in the Rare Disease Database.)

Diagnosis
Affected babies are usually recognized at birth. It is possible for them to be recognized prenatally but there are no definitive prenatal tests for the disorder.

Treatment
Treatment for patients with focal dermal hypoplasia is directed at the symptoms. Dermatological creams may relieve skin discomfort. Dentures and hearing aids may be required. Heat and over-exercise should be avoided. Limb deformities may be treated with surgery.

Genetic counseling may be of benefit for patients and their families.

The identification of the genetic mutation associated with most cases of this syndrome was an important step in understanding and eventually treating the condition.

The study was lead jointly by Xiaoling Wang, Department of Obstetrics and Gynecology at Baylor College of Medicine, and V. Reid Sutton, Department of Molecular and Human Genetics at Baylor College of Medicine.

More 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 website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

The National Foundation for Ectodermal Dysplasias (NFED) sponsors research on ectodermal dysplasias. For information on current and completed studies, contact NFED (see the Resources section of this report.

McKusick VA, ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Focal Dermal Hypoplasia. Entry Number; 305600: Last Edit Date; 3/17/2004.

TEXTBOOK
Buyce ML. Editor-in-Chief. Birth Defects Encyclopedia. Blackwell Scientific Publications. Center for Birth Defects Information Services, Inc., Dover, MA; 1990:516-17.

Jones KL. ed. Smith’s Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:532-33.

Gorlin RJ, Cohen MMJr, Levin LS, eds. Syndromes of the Head and Neck. 3rd ed. Oxford University Press, London, UK; 1990:472-74.

JOURNAL ARTICLES
Rosen SA, Bocklage T, Clericuzio CL. Mucocutaneous squamous papilloma with reactive lymphoid hyperplasia in two patients with focal dermal hypoplasia. Pediatr Dev Pathol. 2005;8:250-52.

Sacoor MF, Motswaledi MH. Three cases of focal dermal hypoplasia (Goltz syndrome). Clin Exp Dermatol. 2005;30:35-37.

Loguercio Leite JC, Faermann R, Rodrigues Stein N, et al. Focal dermal hyperplasia associated with split sternum—Goltz syndrome. Clin Dysmorphol. 2005;14:37-39.

Ogunbiyi AO, Adewole IO, Ogunleye O, et al. Focal dermal hyperplasia: a case report and review of the literature. West Afr J Med. 2003;22:346-49.

Van den Veyver IB. Microphthalmia with linear skin defects (MLS), Aicardi, and Goltz syndromes: are they X-linked dominant male-lethal disorders. Cytogenet Genome Res. 2002;99:289-96.

Fryssira H, Papathanassiou M, Barbounaki J, et al. A male with polysyndactyly, linear skin defects and sclerocornea. Goltz syndrome versus MIDAS. Clin Dysmorphol. 2002;11:277-81.

Hancock S, Pryde P, Fong C, et al. Probable identity of Goltz syndrome and Van Allen-Myhre syndrome: evidence from phenotypic evolution. Am J Med Genet. 2002;110:370-79.

FROM THE INTERNET
Lee W, Goltz RW. Focal Dermal Hypoplasia Syndrome. Last Updated: February 10, 2005. 18pp.
www.emedicine.com/derm/topic155.htm

Goltz-Gorlin Syndrome. Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndrome. Jablonski’s Syndromes Database. nd. 5pp.
www.nlm.nih.gov/jablonski/syndrome_cgi?index=322