Diagnosis: X-linked dominant chondrodysplasia punctata (Conradi-Hünermann-Happle Syndrome)

European Journal of Dermatology. Volume 11, Number 4, 389-91, July - August 2001, Votre diagnostic ?

Author(s) : A. Krisp, A. Konig, R. Hoffmann, R. Happle, Department of Dermatology, Philipp University, Deutschhausstr. 9, 35033 Marburg, Germany.

Summary : A 34-year-old woman was presented with a teleangiectatic nevus on her neck (Fig. 1) and patchy alopecia on her frontal scalp (Fig. 2). Further clinical examination revealed some areas of patchy and cicatrical alopecia with coarse and lusterless hair at the margin (Fig. 3). A third area showing erythematous atrophoderma (Fig. 4) was also observed. Histopathological examination of one of these areas showed hyperkeratosis, paucity of hair follicles and prominent dilation of infundibula with follicular plugging of the remaining hair follicles. Moreover, a dysplasia of the left hand (Fig. 5) and foot (Fig. 6) was noted. No other skin lesions could be found and blood chemistry was unremarkable. The patient was of normal mental development. None of her family members was affected by similar symptoms.

ARTICLE

A 34-year-old woman was presented with a teleangiectatic nevus on her neck (Fig. 1) and patchy alopecia on her frontal scalp (Fig. 2). Further clinical examination revealed some areas of patchy and cicatrical alopecia with coarse and lusterless hair at the margin (Fig. 3). A third area showing erythematous atrophoderma (Fig. 4) was also observed.

Histopathological examination of one of these areas showed hyperkeratosis, paucity of hair follicles and prominent dilation of infundibula with follicular plugging of the remaining hair follicles.

Moreover, a dysplasia of the left hand (Fig. 5) and foot (Fig. 6) was noted. No other skin lesions could be found and blood chemistry was unremarkable. The patient was of normal mental development. None of her family members was affected by similar symptoms.

Diagnosis: X-linked dominant chondrodysplasia punctata
(Conradi-Hünermann-Happle Syndrome)

These findings are characteristic of X-linked dominant chondrodysplasia punctata (Conradi-Hünermann-Happle Syndrome, CDPX2; MIM 302960) which was described as a distinct clinicogenetic entity by Happle et al. in 1977 [1]. Affected women show stippled epiphyseal calcifications, asymmetrical skeletal dysplasia, cataracts and atrophic skin lesions in a patchy or linear distribution following the pattern of Blaschko's lines. CDPX2 is almost exclusively seen in women because the underlying gene defect at Xp11.22-p11.23 is a lethal factor for male embryos.

Dermatological and ophthalmological features

The neonate skin shows irregular zones of inflammation and scaling. These lesions disappear spontaneously after some weeks and form widespread band-like or patchy areas of atrophy. Multiple small pitted areas representing atrophic infundibula of follicles are noted, especially on the forearms. On the scalp a cicatricial alopecia with a margin of coarse and lusterless hair can be found. These asymmetrical skin lesions follow the lines of Blaschko. Ophthalmological findings include cataracts that are either congenital or develop early in life. The lenticular opacities may be either unilateral or bilateral with asymmetric intensity [2].

Pathogenesis

X-linked dominant chondrodysplasia punctata is caused by mutations in the gene EBP at Xp11.22-11.23 [3] which encodes a 3beta-hydroxysteroid-delta⁸, delta⁷-isomerase that catalyses an intermediate step of the conversion of lanosterol to cholesterol [4]. The asymmetric distribution of band-like skin lesions reflects functional X-chromosome mosaicism [5].

References

1. Happle R, Matthias HH, Macher E. Sex-linked chondrodysplasia punctata? Clin Gen 1977; 11: 73-6.

2. Happle R. X-linked dominant chondrodysplasia punctata: review of literature and report of a case. Hum Gen 1979; 53: 65-73.

3. Has C, Bruckner-Truderman L, Muller D, Floeth M, Folkers E, Donnai D, Traupe H. The Conradi-Hünermann-Happle syndrome (CDPX2) and empamil binding protein: novel mutations, and somatic and gonadal mosaicism. Hum Mol Genet 2000; 9: 1951-5.

4. Bravermann N, Lin P, Moebius FF, Obie C, Moser A, Glossmann H, Wilcox WR, Rmoin DL, Kratz L, Kelley RI, Valle D. Mutations in the gene encoding 3beta-hydroxysteroid-delta⁸,delta⁷-isomerase cause X-linked dominant Conradi-Hünermann syndrome. Nature Gen 2000; 22: 291-4.

5. Dipreta EA, Smith KJ, Skelton H. Cholesterol metabolism defect associated with Conradi-Hünermann-Happle syndrome. Int J Dermatol 2000; 39: 864-50.


		Figure 1. A teleangiectatic naevus on the neck.


		Figure 2. Patchy alopecia and sparse hair on the frontal scalp.


		Figure 3. Cicatricial alopecia with sparse and lusterless hair at the brim.


		Figure 4. Patchy erythematous atrophoderma.


		Figure 5. Dysplasia of the left hand.


		Figure 6. Dysplasia of the left foot.