DISEASE CARD

Disease group Ectodermal displasias
DISEASE NAME NAEGELI-SYNDROME
Synonymous Naegeli-Franceschetti-Jadassohn Syndrome
Estimated prevalence 1/1 000 000 to 1/3 000 000
OMIM 161000
Inheritance Autosomal dominant
Gene (s) KRT14 (148066)

Definition

Naegeli-Franceschetti-Jadassohn (NFJ) syndrome is a rare ectodermal dysplasia that affects the skin, sweat glands, nails, and teeth. NFJ was first described in a father and his two daughters by Naegeli in 1927 [1] and was re-evaluated in the same family by Franceschetti and Jadassohn in 1954 [2]. Several families with multiple affected members from several generations have been reported so far. NFJ is inherited as an autosomal dominant condition and is caused by mutations in the KRT14 gene (17q11.2-17q21) [3, 4]. Males and females are equally affected.

Clinical Description

The clinical features of NFJ are absence of dermatoglyhics (no fingerprints), reticular cutaneous hyperpigmentation and hypohidrosis [5]. Hyperpigmentation starts at about the age of 2 years without a preceding inflammatory stage, fades with puberty and sometimes disappears with old age [6, 7]. Hypohidrosis, the most problematic symptom of NFJ patients, is due to diminished sweat gland function, and remains constant throughout adulthood. NFJ patients further show discomfort provoked by heat, nail dystrophy, tooth enamel defects, and moderate hyperkeratosis of the palms and soles. Teeth are always severely affected, leading to early total loss. Diffuse palmoplantar keratoderma may coexist with punctate keratoses that are sometimes accentuated in the creases or exhibit a linear pattern. Congenital misalignment of the great toenails was reported in some patients.

Pathogenesis

NFJ associated KRT14 mutations affect the non-helical head domain (E1/V1) and were predicted to result in very early termination of translation [8]. The data suggest that such KRT14 mutations affect the ontogenesis of dermatoglyphics and sweat glands. Furthermore, the N-terminal part of keratin molecules conferes protection to proapoptotic signals, and patient skin biopsy examination provided evidence for increased TNF-alpha mediated apoptotic activity in the basal cell layer[9].

Diagnosis

Diagnosis is based on the typical clinical features and can be confirmed by molecular analysis. Differential diagnoses include incontinentia pigmenti, dermatopathia pigmentosa reticularis, dyskeratosis congenita, pachyonychia congenita and Dowling-Degos disease. Prenatal diagnosis has not been reported so far.

Treatment

Treatment is symptomatic. The dry skin has to be moisturized with emollients, and hyperthermia should be prevented by use of appropriate clothing and physical cooling with wet dressings or cool water during warm periods. Dental care is imperative to prevent caries and tooth loss.

References

1
Naegeli B. (1927) Familiarer Chromatophorennavus. Schweiz. Med. Wschr. 8: 48.

2
Franceschetti A, Jadassohn W. (1954) A propos de l'incontinentia pigmenti, delimitation de deux syndromes differents figurant sous le meme terme. Dermatologica 108: 1-28.

3
Whittock NV, Coleman CM, McLean WHI, Ashton GHS, Acland KM, Eady RAJ, McGrath JA. (2000) The gene for Naegeli-Franceschetti-Jadassohn syndrome maps to 17q21. J Invest Derm 115: 694-698.

4
Sprecher E, Itin P, Whittock NV, McGrath JA, Meyer R, DiGiovanna JJ, Bale SJ, Uitto J, Richard G. (2002) Refined mapping of Naegeli-Franceschetti- Jadassohn syndrome to a 6cM interval on chromosome 17q11.2-q21 and investigation of candidate genes. J Invest Dermatol 119(3):692-8.

5
Sparrow GP, Samman PD, Wells RS. (1976) Hyperpigmentation and hypohidrosis (the Naegeli-Franceschetti-Jadassohn syndrome): report of a family and review of the literature. Clin Exp Derm 1: 127-140.

6
Itin PH, Lautenschlager S, Meyer R, Mevorah B, Rufli T. (1993) Natural history of the Naegeli-Franceschetti-Jadassohn syndrome and further delineation of its clinical manifestations. J Am Acad Derm 28: 942-950.

7
Itin PH, Burger B. (2010) Spontaneous Fading of Reticular Pigmentation in Naegeli-Franceschetti-Jadassohn Syndrome . Dermatology 221:135-136.

8
Lugassy J, Itin P, Ishida-Yamamoto A, Holland K, Huson S, Geiger D, Hennies HC, Indelman M, Bercovich D, Uitto J, Bergman R, McGrath JA, Richard G, Sprecher E. (2006) Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14. Am J Hum Genet 79: 724-730.

9
Lugassy J, McGrath JA, Itin P, Shemer R, Verbov J, Murphy HR, Ishida-Yamamoto A, Digiovanna JJ, Bercovich D, Karin N, Vitenshtein A, Uitto J, Bergman R, Richard G, Sprecher E. (2008) KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome. J Invest Dermatol 128:1517-24.