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.
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. Enlargement of capillaries/veins under the skin (telangectasias) often develop with ate. 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 affected individuals 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 affected individuals 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.
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:
For information about clinical trials conducted in Europe, contact:
Van den Veyver IB, Sutton VR. Goltz Syndrome (Focal Dermal Hypoplasia). In: Sheffield V, Wynshaw-Boris A, Erickson RP, eds. Inborn Errors of Development. Oxford University Press, 3rd edition, 2014.
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.
Bostwick B, Fang P, Patel A, Sutton VR. Phenotypic and molecular characterization of focal dermal hypoplasia in 18 individuals. Am J Med Genet C Semin Med Genet. 2016 Mar;172(1):9-20. doi: 10.1002/ajmg.c.31473. Epub 2016 Feb 7.
Bree AF, Grange DK, Hicks MJ, Goltz RW. Dermatologic findings of focal dermal hypoplasia (Goltz syndrome). Am J Med Genet C Semin Med Genet. 2016 Mar;172(1):44-51. doi: 10.1002/ajmg.c.31472. Epub 2016 Feb 9.
Smith A, Hunt TR 3rd. The orthopedic characterization of Goltz syndrome. Am J Med Genet C Semin Med Genet. 2016 Mar;172(1):41-3. doi: 10.1002/ajmg.c.31470. Epub 2016 Feb 11.
Wright JT, Puranik CP, Farrington F. Oral phenotype and variation in focal dermal hypoplasia. Am J Med Genet C Semin Med Genet. 2016 Mar;172(1):52-8. doi: 10.1002/ajmg.c.31478. Epub 2016 Feb 3.
Deidrick KK, Early M, Constance J, Stein M, Fete T. Cognitive and psychological functioning in focal dermal hypoplasia. Am J Med Genet C Semin Med Genet. 2016 Mar;172(1):34-40. doi: 10.1002/ajmg.c.31471. Epub 2016 Jan 28.
Sutton VR, Van den Veyver IB. Focal Dermal Hypoplasia. 2008 May 15 [Updated 2013 Apr 11]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1543/ Accessed March 24, 2016.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Focal Dermal Hypoplasia. Entry Number; 305600: Last Update: 02/29/2016.Available at: http://omim.org/entry/305600 Accessed March 24, 2016.
Goltz RW. Focal Dermal Hypoplasia Syndrome. Medscape Reference. Last Update: Feb 19, 2016. Available at: http://emedicine.medscape.com/article/1110936-overview Accessed March 24, 2016.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100