Naegeli-Franceschetti-Jadassohn Syndrome Clinical Presentation

Updated: Aug 30, 2018
  • Author: Rebekah H Clifford, MD; Chief Editor: Dirk M Elston, MD  more...
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Compared with reticulate hyperpigmentation, which fades, hypohidrosis and palmoplantar keratoderma usually persist in Naegeli-Franceschetti-Jadassohn (NFJ) syndrome. In a reexamination of the original family, the natural history of the syndrome was described. The pedigree now documents findings in 6 generations including 62 members with 14 persons affected by NFJ syndrome.

Further data have been accumulated from the original family with NFJ syndrome. Mevorah et al examined 2 patients and documented a mild reduction in the number of functional sweat glands when they were exposed to moderate heat stress. [15] However, the patients remained comfortable and had normal thermal regulation. In addition, Frenk et al performed an electron microscopic study of skin samples from 2 members in the original family. [16] Pigment incontinence was accompanied by varying amounts of colloid-amyloid bodies in the papillar dermis and occasionally around sweat glands in the reticular dermis. This finding is also described in incontinentia pigmenti. [17]


Physical Examination

The main syndrome of Naegeli-Franceschetti-Jadassohn (NFJ) syndrome, an ectodermal dysplasia, is heat intolerance worsened by reduced sweating, with a potential to cause collapse, flushing, and dizziness after even mild exercise. Clinically, patients lack dermatoglyphics, or fingerprint lines, as shown below.

Lack of dermatoglyphics in a patient with Naegeli- Lack of dermatoglyphics in a patient with Naegeli-Franceschetti-Jadassohn syndrome.

Patients also have a characteristic reticular pigmentation, without a preceding inflammatory stage, on their neck, chest, and abdomen, that begins when they are aged 1-5 years and improves after puberty. In many cases, the pigmentation completely resolves at adolescence. In addition, increased spotlike pigmentation may be present around the mouth and eyes. Note the images below.

Reticulated pigmentation on the trunk in a patient Reticulated pigmentation on the trunk in a patient with Naegeli-Franceschetti-Jadassohn syndrome.
Periorbital reticulated pigmentation in a patient Periorbital reticulated pigmentation in a patient with Naegeli-Franceschetti-Jadassohn syndrome.

Affected individuals have mild palmoplantar keratosis, depicted below, brittle fingernails, and defective tooth enamel with a rough surface and yellow spots (shown below). Many patients may develop complete loss of adult teeth. [18, 19, 20]

Spotty palmoplantar hyperkeratosis in Naegeli-Fran Spotty palmoplantar hyperkeratosis in Naegeli-Franceschetti-Jadassohn syndrome.
Defective denture with yellow spots on the enamel Defective denture with yellow spots on the enamel in a patient with Naegeli-Franceschetti-Jadassohn syndrome.

To date, all patients reported had normal intelligence and were usually in good health. Malalignment of the great toenails, bullae, and periungual and mucosal pigmentation are only rarely observed. [20, 21]

Several slightly different clinical phenotypes and intrafamilial variability are also reported. [20, 22, 23, 24, 21, 14, 25] An additional patient with greater variation from the phenotype was identified in Greece. [26] In this patient's family, the reticular hyperpigmentation was accentuated on the flexural areas of the arms and legs; neck; axillae; and cruroinguinal, antecubital, and popliteal regions, where extensive milia formation was observed. The formation of milia had not been reported in the other patients. In the father and grandfather of this patient, the generalized reticular hyperpigmentation was reported to have faded in adulthood. The hyperpigmented macules varied in color (brown to black), pattern, and distribution. Some of the macules were frecklelike or angulated, and they tended to form a reticulate pattern. Others had a mottled pattern or formed streaks and whorls.

Bela et al reported an additional case they believe to be an example of NFJ syndrome with pigmentary dilution of the hair not previously reported. The patient was a 27-year-old man with hypohidrosis and heat intolerance; photophobia; reticulate and mottled pigmentation of the whole body, including the hands, feet, elbows, knees, and tongue; yellow teeth with enamel defects; atrophic skin of the hands and feet; dystrophy of all the nails; mild pigmentary dilution of the hair; and an absence of dermatoglyphics. The patient had molecular analysis for KRT 14 exons 1, 4, and 6 and lacked a mutation. The authors believe the case to be representative of NFJ syndrome and stipulate that further sequencing studies of KRT 14 are needed to diagnose this patient. [27]