NORD gratefully acknowledges Kristina Bundra, NORD Editorial Intern, and V. Reid Sutton, MD, Associate Professor, Department of Molecular & Human Genetics, Baylor College of Medicine/Texas Chidlren’s Hospital, for assistance in the preparation of this report.
Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is a rare multisystem disorder that principally involves the development of the skin, hands and feet and eyes. It is a type of ectodermal dysplasia, a group of heritable disorders causing the hair, teeth, nails, and glands to develop and function abnormally. A majority of the cases of FDH (about 90 percent) are seen in females. This disorder is characterized by skin abnormalities that develop into streaks or lines of tumor-like lumps on various parts of the body. This syndrome displays a wide array of symptoms and may affect almost any organ. FDH is caused by mutations or duplications/deletions in the PORCN gene.
FDH is a rare disorder that primarily affects females and has extreme variability. It is characterized by skin lesions that look streaked, underdeveloped or “punched-out”, birth defects of the hands and feet and birth defects of the eyes. There may be inflammation, itching, reddening, blistering, and crusting of the skin. Skin may be absent, discolored or lack color (pigmentation) in some areas. The nails may be absent or appear abnormal. Wart-like growth (papillomas) are usually not present at birth but develop with age and are typically found on the gums, tongue, lips, nose, genetalia, and anus. 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. Nearly all individuals with focal dermal hypoplasia display at least a few of the skin abnormalities. The hair may be sparse, brittle, and/or missing.
Eye abnormalities are common and are present at birth and can include: 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).
Individuals with FDH may also have a variety of skeletal abnormalities, some of which may be present at birth. Curvature of the spine (scoliosis), 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. Cleft lip and palate may be present and may cause feeding, breathing, and vision problems.
Problems within the mouth are seen in more than 50 percent of patients affected. 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. Abnormalities within the gastrointestinal system may lead to problems with breathing and feeding. Intellectual disability can be found in some instances. Most patients with FDH are noted to be small at birth and have mild short stature.
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 all cases of FDH. 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. Recent studies of patients displaying symptoms consistent with FDH have found mutations or deletions in the PORCN gene in nearly all affected females.
The PORCN gene is found on the X chromosome, and the syndrome is 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. Thus, the identified location of the PORCN gene is Xp11.23.
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 caused by an abnormal gene on the X chromosome and occur mostly in females. Females with these rare conditions are affected when they have an X chromosome with the gene for a particular disease. Males with an abnormal gene for an X-linked dominant disorder are more severely affected than females and often do not survive. Living males with FDH are “mosaic” for a change in the PORCN gene. This means that the change is seen in some, but not all, of the cells in their body.
Prevalence estimates are not available for FDH. Approximately 200 to 300 cases have been reported worldwide, and only about 10 percent are live born males.
Diagnosis is based on clinical findings and affected babies are usually recognized at birth. DNA testing for the PORCN gene is available to confirm the diagnosis.
Clinical Testing and Workup
The diagnosis of focal dermal hypoplasia should be considered in patients with either of the following: multiple skin manifestations or one typical skin manifestation in addition to characteristic limb malformations. In order to better establish the extent of the disease and the treatment of the patient diagnosed, the following evaluations are often recommended: chest x-ray, eye exams, abdominal MRI, kidney ultrasound, hearing evaluation, and medical genetics consultation.
Treatment for patients with focal dermal hypoplasia is directed at the symptoms. Dermatological creams and protective dressings may relieve skin discomfort and prevent secondary infections. Dentures and hearing aids may be required. Heat and over-exercise should be avoided. Limb deformities may be treated with occupational therapy, assistive devices, or surgery. Surgical or laser therapy may be recommended for patients demonstrating trouble swallowing due to large fat deposits in the throat.
Genetic counseling may be of benefit for patients and their families.
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