ARTICLE Speckled
lentiginous nevus consists of a café-au-lait macule superimposed
by multiple dark brown or black dots that represent macular or papular melanocytic
lesions (Fig. 1) [1, 2].
Some authors use the term "nevus spilus" as a synonym [3], and French dermatologists
describe the lesion as "naevus sur naevus" [4]. Other authors have confusingly
and interchangeably used the terms speckled lentiginous nevus, zosteriform
lentiginous nevus, and partial unilateral lentiginosis [1, 5].
The purpose of this article is to draw attention to the fact that speckled
lentiginous nevus may be associated with neurological abnormalities in
the form of a distinct neurocutaneous phenotype for which the new term
"speckled lentiginous nevus syndrome" is proposed.
Speckled lentiginous nevus occurs as
part of phacomatosis pigmentokeratotica
Phacomatosis pigmentokeratotica is characterized by the coexistence
of sebaceous nevus and speckled lentiginous nevus, in the form of a twin
spot phenomenon [6]. In the past, this complex neurocutaneous phenotype
has been further established by additional case reports [7-11]. The component
of sebaceous nevus implies that the spectrum of extracutaneous anomalies
as found in Schimmelpenning syndrome may be part of phacomatosis pigmentokeratotica.
However, extracutaneous anomalies that are usually absent in Schimmelpenning
syndrome have likewise been reported [6, 8].
The spectrum of extracutaneous anomalies of
phacomatosis pigmentokeratotica differs from that
of Schimmelpenning syndrome
In patients affected with phacomatosis pigmentokeratotica, the associated
neurological abnormalities include hyperhidrosis, muscular weakness and
dysesthesia [8]. These neurological defects tend to be ipsilateral with
the speckled lentiginous nevus, and the areas of hyperhidrosis usually
correspond to that of the speckled lentiginous nevus. Hence, these neurological
abnormalities may be best explained as being inherent in the component
of speckled lentiginous nevus.
The twinned components of phacomatosis pigmentokeratotica
may occur separately
Twin spots are defined as paired patches of mutant tissue that differ
genetically from each other and from the heterozygous background tissue
[12]. An embryo may be doubly heterozygous in a way that two different
mutations involve either of a pair of homologous chromosomes. At an early
developmental stage, postzygotic recombination may give rise to two daughter
cells that are homozygous for either mutation, and these would be the
stem cells of two different homozygous skin lesions.
For obvious reasons, the underlying mutations may occur rather often
in an isolated form, and loss of heterozygosity at an early developmental
stage would then give rise to one single mosaic skin disorder [12]. For
example, Schimmelpenning syndrome usually occurs without any twin spot
phenomenon. Only on rare occasions, phacomatosis pigmentokeratotica [6]
or didymosis aplasticosebacea [13] may occur.
Similarly, the component of speckled lentiginous nevus as observed in
phacomatosis pigmentokeratotica would be expected to occur rather often
as an isolated mosaic disorder. However, from the spectrum of extracutaneous
anomalies as reported in phacomatosis pigmentokeratotica one may conclude
that patients with a large speckled lentiginous nevus should sometimes
show hyperhidrosis, abnormal muscular function, dysesthesia or other neurological
defects. For this separate neurocutaneous phenotype the new term "speckled
lentiginous nevus syndrome" is proposed.
Case reports that may be categorized as examples
of speckled lentiginous nevus syndrome
Brufau et al. [4] described a 27-year-old man with a speckled
lentiginous nevus involving the right half of the thorax as well as the
right arm. In addition, hypertrophy of the underlying pectoralis muscles
was noted.
Holder et al. [5] reported on a 43-year-old woman with "partial
unilateral lentiginosis associated with blue nevi". The authors stated
that "such lesions have been described by a number of terms, including
nevus spilus, speckled lentiginous nevus, zosteriform lentiginous nevus,
and partial unilateral lentiginosis". A clinical photograph of the skin
lesion is reminiscent of a speckled lentiginous nevus. The patient developed
at the age of 14 years an unexplained ipsilateral popliteal nerve palsy.
An exploratory operation revealed slight proximal thinning of the nerve.
Electrocardiography showed a right bundle branch block.
Piqué et al. [14] observed a 15-year-old boy with "partial
unilateral lentiginosis" involving the left side of the abdomen and the
lumber area. In addition, sensory and motor neuropathy of the left leg
was noted.
Hofmann et al. [15] described a 30-year-old man with a unilateral,
systematized speckled lentiginous nevus. The speckled component consisted
in part of blue nevi. In addition, the patient showed ipsilateral spinal
muscular atrophy with fasciculation of the arm.
Remarkably, all of the neurological abnormalities as reported in these
cases were ipsilateral to the speckled lentiginous nevus (Table
I).
Tentative genetic classification of the postulated
new phenotype
In analogy to Schimmelpenning syndrome, speckled lentiginous nevus syndrome
will usually occur as a sporadic trait. However, because sebaceous nevus
and Schimmelpenning syndrome can today be categorized as possible examples
of paradominant transmission [16], one may assume that both speckled lentiginous
nevus and speckled lentiginous nevus syndrome may likewise be observed,
by way of exception, in several members of a family [17]. Hence, the postulated
speckled lentiginous nevus syndrome may represent a further example of
paradominant inheritance [18].
Differential diagnosis of speckled lentiginous
nevus syndrome
The postulated new phenotype should be distinguished from cases of partial
unilateral lentiginosis associated with segmental neurofibromatosis [19].
On the other hand, all cases of phacomatosis pigmentokeratotica [6-11]
can be categorized as a particular subtype combining the features of speckled
lentiginous nevus syndrome and those of Schimmelpenning syndrome.
CONCLUSION
The concept of twin spotting in human skin has been established on the
basis of clinical evidence [12]. This theory helps us to understand phacomatosis
pigmentokeratotica and to delineate the speckled lentiginous nevus syndrome.
Within the spectrum of phacomatosis pigmentokeratotica, Schimmelpenning
syndrome may be categorized as one isolated half of phacomatosis pigmentokeratotica,
whereas speckled lentiginous nevus syndrome would represent the other
half of this twin nevus syndrome. The full spectrum of possibly associated
anomalies is so far unknowm.
Future clinical studies will probably confirm that speckled lentiginous
nevus syndrome exists as a distinct neurocutaneous phenotype that usually
occurs as an isolated entity but may sometimes be associated with sebaceous
nevus or Schimmelpenning syndrome in the form of phacomatosis pigmentokeratotica.
Article accepted on 05/01/02
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