ARTICLE
Proteus syndrome was defined in 1979 by Cohen and Hayden and characterized
in 1983 by Wiedemann [1-3] as a rare hamartomatous disorder showing a
wide range of abnormalities. The clinical manifestations include partial
gigantism of the hands or feet, macrodactyly, plantar/palmar hyperplasia,
hemangiomas, lipomas, lymphangiomas, varicosities, epidermal and connective
tissue nevi, cranial exostoses, macrocephaly and skeletal anomalies [4,
5]. About 150 cases have been reported in the literature, but this
number is probably underestimated because of the difficulties in diagnosing
mild forms [6]. Several authors have suggested a score index in order
to establish the diagnosis [2, 5, 7]. Furthermore, follow-up of these
patients is necessary in order to recognize possible additional signs
of the disease and to evaluate the evolution of the lesions over time
[8, 9].
Case report
A 33 year-old male, Caucasian, was affected from birth with an overgrowth
of the fourth finger and palmar hyperplasia of the left hand. For this
problem, he underwent a surgical correction at the age of 13, but overgrowth
recurred after a few years. The patient had a son affected by hexadactyly.
Physical examination showed, on the left palmar surface, a poorly defined
skin-colored mass, with small yellow nodular hyperkeratotic formations resulting
in a cerebriform appearance. The third and fourth fingers of the left hand
were enlarged (Fig. 1).
The soles were normal; lipomas, subcutaneous tumors or other malformations
were absent.
Histopathological examination of the affected fingers revealed a hamartomatous
increase of various components of dermal and subcutaneous tissues, which
appeared otherwise normal; in particular an increased amount of normal looking
collagen fibers was present.
X-rays of patient's hands demonstrated an overgrowth and deformation of
the third and fourth phalanges of the right hand with an increase of soft
tissue. Radiographs of the skull showed a moderate temporo-zygomatic asymmetry.
Routine laboratory exams were in the normal range.
The patient refused to undergo further surgical correction.
Discussion
The Proteus syndrome is a recently described congenital disease characterized
by a great variability of clinical features [9, 10].
Our patient presented macrodactyly, palmar overgrowth of one hand and temporo-zygomatic
asymmetry for many years and was misdiagnosed since few clinical manifestations
were present. Infact, the major question with regard to the diagnosis of
Proteus syndrome is its variability and different expression in each case.
Therefore, it may be confused with numerous syndromes, above all with Klippel-Trenaunay
syndrome and hemihyperplastic lipomatosis syndrome [9, 11]. Recently, some
authors proposed clinical general and specific diagnostic criteria [12]
(Table I). Macrodactyly
and cerebriform appearance of the palmar/plantar surface are considered
clinical hallmarks of the Proteus syndrome by several authors [13-15]. This
is in contrast to other authors who state that a diagnosis of Proteus syndrome
cannot be made on the basis of this anomaly alone [9].
Abnormalities and dysmorphic features evolve
postnatally with time: involvement is asymmetric. The progressive course
of facial dysmorphism, that can affect the Proteus craniofacial skeleton,
could be explained by four types of abnormal growth occurring with various
frequencies and acting either singly or in various combinations. They
can be distinguished as: (1) development of hyperostoses (common, major
effect); (2) unilateral condylar hyperplasia (probably common in occurrence,
but usually minor in effect); (3) abnormal calvarial remodeling and (4)
craniosynostosis (apparently rare, major in effect) [10].
Few cases of the mild form of Proteus syndrome characterized by only one
or two abnormalities have been reported in the literature [15, 16].
Genetic transmission of Proteus syndrome is still
unclear and several hypotheses have been made [6, 9, 13, 17]. The variability
of the clinical expression of Proteus syndrome has been explained by a
mosaicism [18]. Happle suggested that the disease is due to an autosomal
dominant lethal gene surviving by mosaicism [17, 18]. In this way, it
can not be transmitted to another individual because the underlying gene,
when present in the zygote, leads to early death of the embryo. Cells
carrying the mutation can survive only in a mosaic state, when they are
intermingled with normal cells [18, 19]. This mosaic may arise either
from a half chromatid mutation that occurs before fertilization in one
of the two gametes forming the zygote, or from a postzygotic mutation,
during the first steps of embryogenesis [19]. Some authors have also proposed
that this somatic lethal mutation could affect receptors with subsequent
alteration in production and regulation of local tissue growth factors,
and this hypothesis could explain the phenotypic differences from patient
to patient [6]. Some clinical criteria support the hypothesis of a somatic
mosaicism [20]. These criteria include: sporadic occurrence, sex ratio
1:1, mosaic distribution of lesions (which follow lines of Blaschko),
and variable extent of involvement but never diffuse involvement of the
entire body or one entire organ system [12, 20].
CONCLUSION
We suggest that our patient could represent an expression of the tremendous
variability of this syndrome with a minimal clinical manifestation. Considering
the extreme variability of clinical features present in the Proteus syndrome,
careful follow-up of children with apparently minor abnormalities is advisable
in order not to underestimate this disorder.
Article accepted on 20/12/02REFERENCES
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