Goltz syndrome

Definition

Goltz syndrome, also known as focal dermal hypoplasia or Goltz-Gorlin syndrome, is a rare form of an abnormal skin condition that is believed to be a dominant, X-linked trait. It is named after R. W. Goltz, who first described this syndrome in 1962.

Description

Goltz syndrome is a genetic condition primarily found in females that affects the appearance and function of the skin. An unrelated syndrome, nevoid basal cell carcinoma syndrome (NBCCS), is also known as Gorlin-Goltz syndrome. NBCCS is a non-sex linked dominant disorder characterized by a predisposition to cancer , particularly of the basal cells. Care should be taken not to confuse Gorlin-Goltz syndrome with Goltz, or Goltz-Gorlin, syndrome.

Goltz syndrome has many other synonyms, but it is most often referred to as focal dermal hypoplasia (which can be found in the medical literature abbreviated as FDH, FODH, or DHOF) because of the characteristic, localized (focal) skin (dermal) patches that are thin or absent (hypoplasia). Other synonyms include: combined mesoectodermal dysplasia , congenital ectodermal and mesodermal dysplasia, ectodermal and mesodermal dysplasia with osseous involvement, focal dermal hypoplasia syndrome, and focal dermato-phalangeal dysplasia.

Goltz syndrome is part of a larger family of diseases known as the ectodermal dysplasias, or abnormalities of the skin, hair, teeth, and nails. In Goltz syndrome, the skin abnormalities take the form of areas of thin skin (lesions) where the skin is completely absent, or discolored, itchy, or blistered. Hair may also be missing in patches, and the teeth are usually poorly formed. Nails may also be unusual in appearance. In addition to these characteristics of the skin and related organs, Goltz syndrome affected individuals can also have skeletal malformations and eye problems.

The obvious bodily symptoms of Goltz syndrome are the result of improper functioning of the skin, an organ whose multiple functions are often overlooked. The skin consists of two layers, the outer skin (epidermis) and the lower skin (dermis). The epidermis layer protects the body from environmental threats such as temperature variations, bacterial infections, and toxic chemicals. In Goltz syndrome, the epidermis is deformed or completely absent. The dermis layer contains cells, which manufacture the protein collagen. Collagen makes up about one-fourth of all the body's protein and plays a vital role in wound healing, skin and muscle support, and bone formation. In Goltz syndrome, abnormal formation of type IV collagen has been found in the dermis including loose collagen bundles and fibers with loss of regular bands. The importance of collagen for many of the body's tissues explains the varied symptoms of Goltz syndrome, which is observed in parts of the body as different as the bones, skin, hair, and fingernails.

Genetic profile

The locus of the gene responsible for Goltz syndrome has been localized to the short arm of the X chromosome at locus Xp22.3. At or near this same locus is the gene responsible for microphthalmia with linear skin defects (MLS) and the gene responsible for Aicardi syndrome . Because of the relatively low number of males diagnosed with this condition, it is assumed that Goltz syndrome is dominant and X-linked with close to 100% fetal mortality in males. Nearly all of the cases of Goltz syndrome are believed to result from de novo mutations (new mutations which occur after conception) since parents of affected individuals have normal chromosomes .

Demographics

As of 1998, 150 cases of Goltz syndrome in females and only 11 cases in males were reported in the medical literature. Goltz syndrome is not linked to any particular sub-populations. It appears with equal frequency in all races and across all geographies. Because it is an X-linked dominant condition, it is observed with a much higher frequency in surviving females than it is in surviving males.

Signs and symptoms

Goltz syndrome is characterized by localized areas of malformed skin (skin lesions) that appear underdeveloped, streaked, or absent. The skin of an individual affected with Goltz syndrome may lack color (pigmentation) in the affected areas or, the skin may look streaked with lines (linear pigmentation). The affected areas may look and feel inflamed or irritated in various ways such as by exhibiting itching, blistering, reddening and swelling, and even crusting and bleeding. Fatty deposits (papillomas) are usually present in areas of typically sensitive skin, such as the gums, lips, tongue, armpits, vaginal opening, and the anus. Nodules of yellowish fatty tissue can grow on the affected skin, particularly in skin folds.

People with Goltz syndrome often experience excessive skin growth in the palms of the hands and on the soles of the feet. Because of this overgrowth of skin layers, increased sweating (hyperhidrosis) is often noticed in these areas. Similarly, because of an undergrowth of skin in other parts of the body, many individuals affected with Goltz syndrome do not sweat normally (hypohidrosis) throughout the rest of their bodies.

Additionally, individuals affected with Goltz syndrome may present patches of hair loss on both their scalps and in their pubic regions. The teeth of Goltz syndrome patients are often malformed, mispositioned, or absent, and cavities are commonplace because of missing or incomplete tooth enamel.

Unusual bone formations are also associated with Goltz syndrome. Missing or extra fingers or toes, webbed fingers or toes, permanently bent fingers or toes, and fusion of bones in the fingers or toes have all been observed in Goltz syndrome. Other skeletal abnormalities such as curvature of the spine, underdevelopment or a protrusion of the lower jaw, and fused vertebrae may also be present.

Individuals diagnosed with Goltz syndrome are likely to exhibit facial asymmetry, underdeveloped ears, wide-set eyes, and a pointed chin. Hearing loss, either developed or from birth, is frequently experienced by individuals affected with Goltz syndrome due to the underdevelopment of the ears. Many eye abnormalities have been seen in those affected with Goltz syndrome. These range from missing eyes (anophthalmia) and incomplete formation of the eye (coloboma ) to clouding of the cornea, drooping eyelids, and crossed eyes. The mucous membranes of the nose and throat may also be affected. Mental retardation has been observed in some, but not all, cases.

Diagnosis

Goltz syndrome is generally diagnosed by the presence of the characteristic skin abnormalities coupled with the characteristic fatty deposits in the gums, lips, armpits, vagina, or anus. It is distinguished from the other possible ectodermal dysplasias by the lack of pigmentation of the skin in some of the affected areas, the abnormal sweating experienced by those individuals affected, the lack of cysts in the eyes, and the presence of tear ducts. The papillomas in the genital areas are often misdiagnosed as genital warts, but Goltz syndrome patients will test negative for human papillomavirus (HPV), the cause of the common genital wart. Prenatal diagnosis is not yet available, but connection to the Xp22.3 locus makes genetic testing for this dominant condition potentially possible. In families with a child affected by Goltz syndrome, a skin test on the parents should be conducted to evaluate the potential risk of a second child being born affected with this syndrome.

Treatment and management

The treatment and management of Goltz syndrome varies according to symptoms observed. Dermatological treatments such as skin creams and more targeted treatments are usually indicated. Some affected individuals will require dental work or surgery. Others will need respiratory therapies to keep the nose and throat clear. Certain skeletal deformations seen in Goltz syndrome patients may be corrected by orthopedic surgery. Because of the associated abnormal sweating patterns, those with Goltz syndrome should not be exposed to heat and should avoid heavy exercise.

Prognosis

Goltz syndrome is thought to be almost always lethal in males. Even so, a male patient as old as 68 has been reported in the medical literature. In females, a full life expectancy is possible if medical treatment is followed.

Resources

PERIODICALS

Buchner, S., and P. Itin. "Focal Dermal Hypoplasia in a Male Patient: Report of a Case and Histologic and Immunohistochemical Studies." Archives of Dermatology (August 1992): 1078-82.

Lee, I., et al. "Electronmicroscopic Observation of the Basement Membrane Zone in Focal Dermal Hypoplasia." Pediatric Dermatology (January-February 1996): 5-9.

Mendez, P., M. Vega, and A. Mosqueda. "Mucosal Lesions in Focal Dermal Hypoplasia Syndrome." Medecina Oral (April 1999): 366-71.

ORGANIZATIONS

Ectodermal Dyplasia Society. 108 Charlton Lane, Cheltenham, GlosGL53 9EA. UK <http://www.ectodermaldysplasia.org>.

National Foundation for Ectodermal Dysplasias. PO Box 114, 410 E Main, Mascoutah, IL 62258-0114. (618) 566-2020. Fax: (618) 566-4718. <http://www.nfed.org>.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.

WEBSITES

"Focal Dermal Hypoplasia." Online Mendelian Inheritance in Man.<http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=305600> (05 February 2001).

"Focal Dermal Hypoplasia." Reader's Digest Health.<http://rdhealth.com/kbase/nord/nord926.htm> (February 5, 2001).

Paul A. Johnson