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.
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Figure 1. A teleangiectatic
naevus on the neck. |
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Figure 2. Patchy
alopecia and sparse hair on the frontal scalp. |
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Figure 3. Cicatricial
alopecia with sparse and lusterless hair at the brim. |
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Figure 4. Patchy
erythematous atrophoderma. |
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Figure 5. Dysplasia
of the left hand. |
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Figure 6. Dysplasia
of the left foot. |
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