ARTICLE
Sir,
In rare instances, patients with autosomal dominant skin disorders such
as actinic porokeratosis and Darier disease, show linear areas of markedly
more severe involvement with respect to the surrounding skin. It has been
hypothesized that this phenomenon is due to an early loss of heterozygosity.
In a heterozygous embryo, a further mutation occurring early in embryonic
life may lead to the formation of a clone of homozygous or hemizygous
cells that develops into a linear area of more severe involvement, usually
following Blaschko's lines [1].
Recently, a 13-year-old girl whom we followed
from birth for KID syndrome, a keratinization disorder characterized by
keratitis, atypical ichthyosis and deafness [2], returned to our department
for follow-up. The girl was born with a congenital erythrokeratoderma
from non-consanguineous, unaffected parents; she had an unaffected sister.
A diffuse thickening of the skin was present since infancy. It was characterized
by homogeneous, spiny, dry hyperkeratotic papules which were disposed
according to the superficial skin markings and gave the surface a "gross
grain leather" appearance. Well demarcated erythematous and scaly plaques
were present in the centro-facial area, on popliteal and antecubital folds,
as well as on the dorsal surface of the hands and feet. A characteristic
reticulated palmoplantar hyperkeratosis was present, and the nails were
dystrophic. Eyebrows and eyelashes were scarce; the scalp hair was normal.
From infancy the patient suffered from severe photophobia and chronic
keratitis with corneal neovascolarization and opacities. A profound bilateral
neurosensory hearing loss was present. The girl did not show mental impairment
and was attending regular classes.
On physical examination we noted on the back
of the patient (level C8) a linear lesion in which the hyperkeratosis
was markedly thicker than that of the surrounding skin (Fig.
1). It was characterized by homogeneous spiny hyperkeratotic papules
that were similar to those covering the surrounding skin, but markedly
more prominent and brownish in color. The lesion started from the midline
and proceeded leftward delineating a curve that corresponded to the Blaschko
lines described for this area. According to the patient's mother, it was
present since infancy.
To our knowledge, a similar linear lesion has not previously been described
in KID syndrome. The observation that the lesion followed Blaschko's lines,
i.e., embryonic lines of development of the skin, and showed a
peculiar spiny hyperkeratosis that was identical, although markedly more
severe with respect to the surrounding skin, leads us to hypothesize that
the lesion may be due to an early postzygotic mutation leading to loss
of heterozygosity.
The alternative hypothesis of an associated
epidermal nevus seems unlikely if one considers the clinical aspect of
the lesion. A biopsy was not permitted by the parents of this patient.
The mode of transmission of KID syndrome is still debated. Three reports
of vertical transmission are described in the literature, suggesting autosomal
dominant transmission [3, 4]. However, a report of two sisters with KID
syndrome born from consanguineous unaffected parents [5], and a report
of two half siblings of different sex born with KID syndrome from two
unaffected and unrelated partners and one unaffected mother [6], lead
some investigators to hypothesize that the disease may be vertically transmitted
as an autosomal recessive trait in a high consanguineous population, a
phenomenon known under the term "pseudodominance". It should be noted,
however, that gonadal mosaicism for an autosomal dominant trait in clinically
unaffected parents could explain the latter cases just as well.
The presence of a patch suggesting loss of heterozygosity
in KID syndrome may be taken as additional evidence for an autosomal dominant
mode of transmission of the syndrome. According to the proposed classification
[1], this case would represent a type 2 segmental manifestation, resulting
from an early change of heterozygosity to either homozygosity or hemizygosity
for the mutation of KID syndrome.
The lack of reports of similar linear lesions is most likely due to
the rarity of the phenomenon, and to the fact that if one is not aware
of the possibility of the appearance of linear arrangement in a generalized
disease, such lesions may easily go unnoticed.
REFERENCES
1. Happle R. A rule concerning the segmental manifestation of autosomal
dominant skin disorders. Review of clinical examples providing evidence
for dichotomous types of severity. Arch Dermatol 1997; 133: 1505-9.
2. Caceres-Rios H, Tamayo-Sanchez L, Duran McKinster C, de la Luz-Orozco
M, Ruiz-Maldonado. Keratitis, ichthyosis, and deafness (KID syndrome):
review of the literature and proposal of a new terminology. R Pediatr
Dermatol 1996; 13: 105-13.
3. Nazzaro V, Blanchet-Bardon C, Lorette G, Civatte J. Familial occurrence
of KID (keratitis, ichthyiosis, deafness) syndrome. Case report of a mother
and a daughter. J Am Acad Dermatol 1990; 23: 385-8.
4. Grob JJ, Breton A, Bonafe JL, Sauvan-Ferdani M, Bonerandi JJ. Keratitis,
ichthyosis and deafness (KID) syndrome: vertical transmission and death
from multiple squamous cell carcinomas. Arch Dermatol 1987; 123:
777-82.
5. Voigtländer V. Hereditäre Verhornungstörungen und
Taubheit. Z Hautkr 1977; 52: 1017-20.
6. Koné-Pault I, Hesse S, Palix C, Rey R, Rémediani K,
Garnier JM, Berbis P. Keratitis, Ichtyosis, and deafness (KID) syndrome
in half sibs. Pediatr Dermatol 1998.
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