ARTICLE In
this issue, Assmann et al. [1] describe the Buschke-Ollendorff syndrome
in a 5-year-old boy who showed multiple yellowish or skin-colored papules
and plaques involving the right flank and thigh in a segmental arrangement.
The diagnosis of Buschke-Ollendorff syndrome was confirmed by X-ray examination
revealing osteopoikilosis of the right hand and the right foot. The authors
emphasize that such early onset of cutaneous and bony lesions of the disorder
is quite unusual.
How can we explain the precocious, unilateral and pronounced manifestation
of this phenotype? Recently a rule of dichotomous types of segmental manifestation
of autosomal dominant skin disorders has been proposed [2]. The type 1
reflects heterozygosity for a postzygotic new mutation, whereas the type
2 results from loss of the corresponding wildtype allele occcurring in
a heterozygous embryo and reflects either homozygosity or hemizygosity
for the underlying mutation, giving rise to a rather pronounced segmental
involvement [3].
Because Assmann et al. report that four other family members
showed lesions of Buschke-Ollendorff syndrome in a mild form, the boy
must be heterozygous for the underlying mutation. This excludes the possibility
of a type 1 segmental manifestation of this disorder.
Rather, this case may represent an example of type 2 segmental manifestation
of Buschke-Ollendorff syndrome. At an early developmental stage, loss
of heterozygosity would have occurred in a somatic cell, giving rise to
a population of cells in which the corresponding wildtype allele is lacking.
This would explain the early onset of pronounced lesions involving a segmental
area of the body. On the basis of several similar case reports collected
from the literature [4-6], this concept has recently been proposed for
the Buschke-Ollendorff syndrome [7].
Because a type 2 segmental manifestation of an autosomal dominant skin
disorder tends to be superimposed on the ordinary nonsegmental phenotype
[3], one may predict that the little boy described by Assmann et al.
will later develop multiple small, disseminated cutaneous lesions as usually
encountered in adults with Buschke-Ollendorff syndrome.
Hence, the unusual case reported by Assmann et al. should not
be simply taken as a "rare butterfly". Rather, it may be of general significance
and provide insight into a mechanism that is more than skin deep..
References
1. Assmann A, Mandt N, Geilen CC, Blume-Peytavi U. Buschke-Ollendorff
syndrome - differential diagnosis of disseminated connective tissue
lesions. Eur J Dermatol 2001; 11: 576-9.
2. 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.
3. Happle R. Loss of heterozygosity in human skin. J Am Acad
Dermatol 1999; 41: 143-61.
4. Smith AD, Waisman M. Connective tissue nevi: familial occurrence
and association with osteopoikilosis. Arch Dermatol 1960; 81: 249-52.
5. Schorr WF, Opitz JM, Reyes CN. The connective tissue nevus-osteopoikilosis
syndrome. Arch Dermatol 1972; 106: 208-14.
6. Lacour M. Buschke-Ollendorff syndrome, Marfan's syndrome,
osteogenesis imperfecta, anetodermas and atrophodermas. In: Harper J,
Oranje A, Prose N (eds), Textbook of pediatric dermatology. Blackwell
Science, Oxford, 2000: 1286-302.
7. Happle R. Segmentale Typ-2-Manifestation autosomal dominanter
Hautkrankheiten: Entwicklung eines neuen formalgenetischen Konzeptes.
Hautarzt 2000; 52: 283-7.
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