Naegeli-Franceschetti-Jadassohn syndrome

BACKGROUND

Naegeli-Franceschetti-Jadassohn (NFJ) syndrome is a form of ectodermal dysplasia that affects the outer layer of a developing baby called the ectoderm. Because the ectodermal layer develops into many parts of the baby's body, including the lens of the eye, parts of the inner ear, fingers, toes, and nerves, these parts may not develop normally.

NFJ syndrome is very rare. It affects only one in 2-4 million people and has been found among families in Switzerland, Japan, Italy, and Greece. Males and females are equally affected.

NFJ syndrome affects the skin, sweat glands, nails, and teeth. Other problems include lack of fingerprints, thickened skin on the palms of the hands and soles of the feet, and fingernail and dental problems.

NFJ was named after the first few scientists who studied it. The symptoms of NFJ syndrome were first described in a Swiss family by Naegeli in 1927. Franceschetti and Jadassohn added to the knowledge of NFJ in the 1950s.

People with NFJ syndrome are of normal intelligence and tend to be in otherwise good health. Although there is no cure for NFJ, most people with the disorder can expect to live long healthy lives.

RISK FACTORS

Naegeli-Franceschetti-Jadassohn (NFJ) syndrome is very rare. It affects only one in 2-4 million people worldwide. NFJ syndrome has been found among families in Switzerland, Japan, Italy, and Greece.

A gene has been identified for anhidrotic ectodermal dysplasia, the family of disorders to which NFJ belongs, but a specific predisposition to NFJ has not been identified.

NFJ syndrome affects males and females equally.

CAUSES

Inheritance: Naegeli-Franceschetti-Jadassohn (NFJ) syndrome is an autosomal dominant condition, meaning only one copy of the mutated gene is necessary for a person to be affected by this condition. People with family histories of NFJ have an increased risk of developing the disorder. Affected individuals usually have one affected parent.

In addition, mutations in the KRT14 gene are responsible for two rare disorders of skin development, including NFJ.

Random occurrence: Random occurrence is a term used to describe a mutation in genes that is not due to any specific cause. It is usually the result of an error in the normal function of enzymes in cells. In some cases, NFJ syndrome may develop due to random occurrence. These individuals may then pass the trait to their children.

SIGNS AND SYMPTOMS

Because people with Naegeli-Franceschetti-Jadassohn (NFJ) syndrome have reduced or absent sweat, they often cannot tolerate hot weather or intense exercise.

Other common symptoms of NFJ syndrome include lack of fingerprint lines, thickness of the skin on the palms of the hands and soles of the feet, and brittle fingernails.

Dental problems of NFJ syndrome include defective tooth enamel with yellow spots, early cavities, and early tooth loss.

Patients also have dark spots on their necks, chests, and abdomens that tend to appear between age one and five. Patients with NFJ syndrome may also have increased dark spots around the mouth and eyes. In many cases, this completely resolves by the teenage years.

Rare symptoms of NFJ syndrome include poor alignment of the toenails on the big toes, dark coloring of the skin around the fingernails and inside the mouth, and small rough spots on the hands.

DIAGNOSIS

General: Because people with Naegeli-Franceschetti-Jadassohn (NFJ) syndrome have reduced or absent sweat, the disease is usually diagnosed early in life. The lack of fingerprint lines (dermatoglyphics) can be easily checked.

Biopsy: A biopsy of the mucous membranes indicates absent or poorly formed mucous membranes. A skin biopsy can indicate absent or poorly formed sweat glands.

Genetic testing: Genetic testing is a type of medical test that identifies changes in chromosomes, proteins, or genes. Usually genetic testing is used to find changes associated with inherited disorders. Genetic testing is available for some types of ectodermal dysplasia but not specifically for NFJ syndrome.

Amniocentesis: Amniocentesis is a medical test in which fluid is removed from the sac around the fetus. This fluid is analyzed for the presence of abnormalities in chromosomes, genes, and proteins. Amniocentesis is performed after week 15 of pregnancy. The procedure carries some risk, such as miscarriage, and may or may not be accurate.

COMPLICATIONS

Because people with Naegeli-Franceschetti-Jadassohn (NFJ) syndrome have reduced or absent sweat, even mild exposure to heat and exercise may cause collapse, flushing, and dizziness.

TREATMENT

General: There is no known treatment for Naegeli-Franceschetti-Jadassohn (NFJ) syndrome.

Hydration: As with other ectodermal dysplasias, exposure to heat should be limited and sufficient hydration is recommended. Exercise should be limited to only moderate activities. Patients with NFJ syndrome can participate in low-impact activities, such as swimming.

Oral hygiene: Regular tooth care to prevent cavities is recommended. People with NFJ should brush their teeth twice a day and/or after meals and should receive regular preventive dental care every six months.

Dermatologic: Application of retinoic acid (a form of vitamin A used to treat skin disorders) and keratolytics (skin softeners) to the palms of the hands and soles of the feet may help the thickening of the skin. Blisters that do not cause scarring are generally temporary and heal without treatment. Cold compresses may be used to treat discomfort.

INTEGRATIVE THERAPIES

Currently, there is not enough scientific data on the use of integrative therapies for the treatment or prevention of Naegeli-Franceshetti-Jadassohn dysplasia.

PREVENTION

There are no known means of preventing Naegeli-Franceschetti-Jadassohn dysplasia.

Genetic counseling is a service that provides information and support to individuals who have or may have genetic disorders. During a genetic counseling session, a genetics specialist meets with the individual and/or the individual's family to discuss the potential for having a child with a genetic condition. Genetic counseling is advised for individuals with a family history of ectodermal dysplasia. In many cases, the condition can be diagnosed before birth.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

• Ectodermal Dysplasia Society. www.ectodermaldysplasia.org. Accessed March 17, 2008.
• Itin PH, Lautenschlager S, Meyer R, et al. Natural history of Naegeli-Franceshetti-Jadassohn syndrome and further delineation of its clinical manifestations. J Am Acad Dermatol. 1994;31(5 Pt 1):830. View abstract
• Kudo Y, Fujiwara S, Takayusu S, et al. Reticulate pigmentary dermatosis associated with hypohydrosis and short stature: a variant of Naegeli-Franceschetti-Jadassohn syndrome? Int J Dermatol. 1995;34(1):30-1. View abstract
• Lugassy J, Itin P, Ishida-Yamamoto A, et al. Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: tow allelic ectodermal dysplasias caused by dominant mutations in KRT14. Am J Hum Genet 2006;79:724-730. View abstract
• Lugassy J, McGrath JA, Itin P, et al. KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn Syndrome. J Invest Dermatol. 2007; Nov 29 [Epub ahead of print] View abstract
• Mevorah B, Frascarolo P, Gianadda E, et al. Sweat studies under conditions of moderate heat stress in two patients with the Nageli-Franceschetti-Jadassohn syndrome. Dermatology. 1993;187(3):174-177. View abstract
• National Foundation for Ectodermal Dysplasias (NFED). www.nfed.org. Accessed March 17, 2008.
• Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2008.
• Sparrow GP, Samman PD, Wells RS. Hyperpigmentation and hypohidrosis. (The Naegeli-Franceschetti- Jadassohn syndrome): report of a family and review of the literature. Clin Exp Dermatol. 1976;1(2):127-40. View abstract
• Tzermias C, Zioga A, Hatzis I. Reticular pigmented genodermatosis with milia—a special form of Naegeli-Franceschetti-Jadassohn syndrome or a new entity? Clin Exp Dermatol. 1995;20(4):331-5. View abstract
• Whittock NV, Coleman CM, McLean WHI, et al. The gene for Naegeli-Franceschetti-Jadassohn Syndrome maps to 17q21. J Invest Dermatol. 2000;115:694-698. View abstract