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LETTER TO JMG
From Aldrovandi’s “
Homuncio
” (1592) to Buffon’s girl
(1749) and the “Wart Man” of Tilesius (1793): antique
illustrations of mosaicism in neurofibromatosis?
M Ruggieri, A Polizzi
.............................................................................................................................
J Med Genet
2003;40:227–232
N
eurofibromatosis type 1 (NF1) and type 2 both occur in
mosaic (segmental) for ms.
1
When NF1 (and other
autosomal dominant skin disorders)
12
occurs in a lin-
ear, patchy, quadrant, or otherwise localised form, two differ-
ent types of mosaicism can be distinguished.
2
Type 1 segmen-
tal involvement reflects heterozygosity for a postzygotic
mutation occurring in an otherwise healthy embryo. The seg-
mental lesions are limited to the affected area and show the
same degree of severity as that found in the corresponding
non-mosaic trait (for example, mosaic/segmental NF1). Type 2
segmental involvement occurs in a heterozygous embryo and
reflects loss of heterozygosity that occurred at an early devel-
opmental stage. Clinically, the lesions of type 2 segmental
involvement are markedly more pronounced and superim-
posed on a milder, non-segmental, heterozygous manifesta-
tion of the same trait.
2
In the light of these concepts of mosai-
cism, we critically reviewed (previously published) antique
illustrations of presumed “full blown” NF1 sufferers.
3–9
We
have diagnosed as having mosaic/segmental NF1 the Indian
man (“Homuncio”) in the “Monstrorum Historia”
10
of the Italian
naturalist and philosopher Ulisse Aldrovandi (1522-1605), the
hor ned monster in “Des Monstres et Prodiges”
11
of the French
surgeon Ambroise Paré (1510-1590), and the goitred woman
in the “Buch der Natur”
12
of the German naturalist Conrad von
Megenberg (1303-1374). Type 2 segmental manifestations of
NF1 were recognisable in Buffon’s girl (1707-1788)
13
and the
“Wart Man” of Tilesius (1793).
14
ALDROVANDI’S DOCUMENTS IN BOLOGNA
In 1592, Ulisse Aldrovandi (1522-1605), an Italian physician,
philosopher, and naturalist,
15
recorded the extraordinary case
of a man of short stature (“Homuncio”), of Indian origin, who
presented enormous, flabby masses of flesh less than two
inches thick hanging from the left side of his head and trunk
(fig 1).
3410
This illustration, along with a Latin text (fig 2),
appeared on pages 587 and 585, respectively, of “Monstrorum
Historia”, published posthumously in 1642 under Aldrovandi’s
name and edited by Bartolomeo Ambrosino.
10
Zanca and
Zanca
34
have stated that this case report is a modified version
of one written by an amanuensis and found among Aldrovan-
di’s documents in the University Library in Bologna in a tome
containing stories and chronicles regarding the period
between 12 November 1592 and June 1593 (f 145, ms 136,
tome XIX).
3
They also implied
34
that this misshapen man
would represent a multiple (type 1) neurofibromatosis-like
case.
579
Figure 1 The illustration of the “
Homuncio
” (p 597) accompanying
Aldrovandi’s case report in “
Monstrorum Historia
” (1642) © S
Karger AG and University Library of Bologna.
Key points
• Neurofibromatosis type 1 (NF1) and type 2 both occur
in mosaic (segmental) forms: the segmental lesions can
be limited either to the affected area showing the same
degree of severity as that found in the corresponding
non-mosaic trait (type 1/segmental involvement) or are
markedly more pronounced and superimposed on a
milder, non-segmental, heterozygous manifestation of
the same trait (type 2 segmental involvement).
• By critically reviewing antique illustrations of presumed
“full blown” NF1 sufferers, we have diagnosed as hav-
ing mosaic/segmental NF1 the Indian man
(“
Homuncio
”) in “
Monstrorum Historia
” by Ulisse
Aldrovandi (1522-1605), the horned monster in “
Des
Monstres et Prodiges
” by the French surgeon Ambroise
Paré (1510-1590), and the goitred woman in “
Buch der
Natur
” by the German naturalist Conrad von Megen-
berg (1303-1374). Type 2 segmental manifestations of
NF1 were recognisable in Buffon’s girl (1707-1788)
and the “Wart Man” of Tilesius (1793).
• These antique illustrations may be considered as the
earliest examples of mosaicism in neurofibromatosis.
227
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THE “HOMUNCIO”
The earlier version (1592) of Aldrovandi’s manuscript has
been transcribed and translated in Italian by Zanca
3
with the
help of R Signorini. The English translation of this original
version reads: “The monster, Homunculus, as refers the
Aegisthus, born in India, of six palms in stature. Between his
mouth and left ear, he had a double fleshy mass hanging for-
ward towards the chest: one [mass] was nearer the mouth, the
other shorter, and adhered to the ear. Behind and under the
left ear, likewise, a similar flesh rolled down dropping over the
shoulder, spread with some tufts of hair as were the former
two [masses] on the left side of his mouth covered with hairs
such as of beard, particularly in the folds. At the beginning of
the chest, under the chin and springing up around almost the
entire chest, another very large and very wide [fleshy mass]
extending from the left shoulder hung downward across
almost the entire abdomen, enlarging from the right breast to
the opposite side or rather the left armpit. Indeed that flesh
and that loose substance was less than two fingers thick and
with the hands it could be raised from the body, as it did not
adhere [to the skin] except in the place of its own origin, up to
the beginning of the chest and over the breasts. That same part
of the body felt exceedingly warm, and therefore it must be
believed that the red portion of the growth could be invaded
by heat of some kind. This monstrous homunculus was
brought to my attention by the Bolognese nobleman Bovio.”
An English translation
5
of the (later) version (fig 2) found
in Aldrovandi’s “Monstrorum Historia ” (1642)
10
contains a few
modifications compared to the earlier version.
3
Zanca
3
purported that the person who carried out the xylo-
graph forgot to copy the drawing in reverse onto the wooden
tablet, so that the illustration, once engraved, showed the
fleshy masses to originate on the right side of the body (fig 1)
rather than the left, as described in the original report found
among Aldrovandi’s documents.
35
ULISSE ALDROVANDI AND HIS TIME: THE
RENAISSANCE CONCEPTION OF MONSTERS
Certainly, Aldrovandi’s Indian man should be viewed in the
context of Renaissance European conceptions of monsters
originating from the old Greek notion of ethnographical mon-
sters, which they imagined to live far away in the east, above
all in India.
35
Indeed, Wittkower
16
describes Aldrovandi as a
scholar of immense erudition but at the same time somewhat
more accepting and uncritical of tales and myths about
human and animal monstrosities, calamities, and political or
religious upheavals of the old authorities than one might
expect.
45
In “Monstror um Historia”, the “fabulous races” appear
one after the other in large woodcuts accompanied by learned
texts. Nonetheless, one feels that we are dealing, in this
instance (figs 1 and 2), with a really scientific illustration
because of the accurac y of detail in the portrait and the
accompanying text and its likeness to the phenotype of a neu-
rofibromatosis sufferer.
It must also be also noted that Aldrovandi used to draw
portraits and engrave thousands of illustrations of animals,
plants, and minerals, of which quite a few are kept in the Uni-
versity Library of Bologna.
31517
Such illustrations are exceed-
ingly accurate (Aldrovandi was among the first to give
importance to colour figures) aiming to form the basis of an
encyclopaedia of natural history in 13 volumes published,
almost entirely posthumously, by Aldrovandi’s pupils who
took 73 years to complete it.
315
In addition, Aldrovandi
reported and illustrated meticulously several dermatological
conditions with monstrosities.
15 17
DID THE “HOMUNCIO” HAVE FULL BLOWN
NEUROFIBROMATOSIS TYPE 1?
Zanca and Zanca
34
based their diagnosis of NF1 on (1) the
appearance of the masses (looking like plexifor m
neurofibromas)
18 19
covered with hairs (similar to the hairy
naevi seen in NF1),
20
and (2) the short stature of the subject (a
minor NF1 feature)
20 21
ascribed to a “grave form of
widespread kyphoscoliosis (an NF1 complication)
20 22
or to a
serious endocrinal alteration”. They implied that “the
phenomenon of striking tumours covered with hairs can be
observed, with or without other congenital anomalies, in von
Recklinghausen disease”.
4
Madigan and Masello,
5
in confirm-
ing the diagnosis of NF1, added macrodactyly of the left sec-
ond toe and leg asymmetry (fig 1) secondary to scoliosis as
additional clinical stigmata of NF1.
REDIAGNOSING THE “HOMUNCIO”: MOSAIC
(SEGMENTAL) NF1
We think that the diagnosis of “full blown” (generalised) NF1
in this case
3–9
should be reconsidered in light of the concept of
mosaicism in the neurofibromatoses
1
and more generally in
human skin disorders.
223
This portrait (fig 1) is a xylograph copy reproducing the
body of the “Homuncio” in its minute detail, the flaccidity of
soft tissues, the skin folds, the lack of adherence of the mass
to the skin, the hairs covering (only) part of the skin in the
nearby area of the mass on the right arm and shoulder, the
(apparent) multiplicity of the masses, are all for the
meticulous reproduction of a patient rather than as an
illustration of a mythological monster. The accompanying
Latin description (fig 2) is even more detailed than the
illustration itself. If the diagnosis were that of “full blown”
NF1 then one would have expected a more “generalised” NF1
phenotype, especially if one considers the associated severe
complications (for example, the plexiform neurofibroma and
Figure 2 The 1642 Latin version in Aldrovandi’s “
Monstrorum
Historia
” (p 585) describing the “
Homuncio
”. Its first lines read
(paragraph E): “In this place also must be considered the Indian man
of short stature with a fleshy substance hanging from [?] the chest.
Passing through Bologna previously in the year 1592 this misshapen
man was brought to the most distinguished gentleman Ulisse
Aldrovandi”. © S Karger AG and University Library of Bologna.
228 Letter
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the scoliosis). Conversely, this detailed case lacks depiction of
other (classical) clinical features of NF1 (for example, café au
lait spots, freckling, or cutaneous neurofibromas). In addition,
the “fleshy” mass seems to originate from a single region
rather than from multiple body areas; thus, it would fit better
with a solitary lesion,
1
as typically occurs with (diffuse) plexi-
for m neurofibromas.
18 19
For the above reasons, in the absence
of other cutaneous stigmata of NF1, we would favour the
diagnosis of mosaic/segmental NF1.
1
In patients with mosaic or localised manifestations of NF1,
disease features are limited to the affected area, which varies
from a narrow strip to one quadrant and occasionally to one
half of the body, either in a symmetrical or asymmetrical
ar rangement.
1
Affected patients may have pigmentary
changes (café au lait spots and/or freckling) alone, neurofibro-
mas alone, a combination of neurofibromas and pigmentary
changes, or solitary plexiform neurofibromas.
119
In this
respect, Aldrovandi’s case would fit with the latter category of
isolated plexiform neurofibroma.
1
The accompanying features
of short stature, leg asymmetry, and macrodactyly have been
previously reported in localised NF1 phenotypes.
1
A solitary
(segmental) lesion would actually better explain the lack of
other cutaneous NF1 features, rather than an oversight or
omission of the portrayer (fig 1) or of Aldrovandi himself (fig
2). Also, the largeness of the mass could be explained by the
concept that in mosaic dermatological phenotypes the disease
manifestation may be more florid in the affected area.
12
One
could also speculate that the short stature and the leg
asymmetry (fig 1) might be related to the regional effect of the
NF1 gene mutation because body mass and height are often
reduced in generalised NF1.
1724
EARLIER ILLUSTRATIONS OF MOSAIC (SEGMENTAL)
NEUROFIBROMATOSIS TYPE 1
It is possible to trace other earlier illustrations, though not so
scientific, of lesions resembling the solitary plexiform
neurofibromas seen in mosaic/segmental NF1. Among the
various figures published in “Des Monstres et Prodiges” by the
famous French surgeon Ambroise Paré (1510-1590) (author
of many books on anatomy, surgery, and medicine)
11
is that of
a monster born on 17 January 1578, in Piedmont, in Chieri,
near Turin, Italy (fig 3).
34
The face, writes Paré “ . . .was well
proportioned in every way, but there were five horn-like
growths on the head and a long, fleshy mass hanging down
from the head along the back” “en maniere d’un chaperon de
damoyselle” (“like a woman’s hat”); “ . . .another double fleshy
mass like a shirt collar was visible around the neck”. Besides
the more or less fantastic deformations (horns, claw-like
hands, etc) and relying on the accuracy with which Paré him-
self reported this case, the fleshy mass hanging down along
the back (fig 3) might be diagnosed as a solitary (diffuse)
plexifor m neurofibroma
1
rather than as a manifestation of
generalised NF1, as postulated by other authors.
3
The Bavarian naturalist and philosopher Conrad von
Magenberg (1309-1374) wrote on theological, historical, and
political arguments, but became famous for divulging the sci-
entific knowledge of his day. In his 12th volume of the Augs-
burg edition of the “Buch der Natur” (1350), there is a
xylograph (fig 4) which illustrates various types of monsters
such as the sciapod with webbed feet, the headless monster
Figure 3 The “horned” monster born on 17 January 1578 in
Piedmont, in Chieri, near Turin, Italy as illustrated in Ambroise Paré’s
“
Des Monstres et Prodiges
”, Paris 1585. © S Karger AG.
Figure 4 The “Human Monsters” from Conrad von Magenberg’s
“
Buch der Natur
”, Augsburg, 1475. In the bottom row, the third
woman from the left has an elongated sack hanging from the
mandible region.
Letter 229
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with six arms, the cinocephalus, and the Cyclops, among oth-
ers. In the bottom row of the xylograph (fig 4), near the
bearded woman, can be seen another woman who, according
to Choulant,
25
has a large goitre and according to Zanca and
Zanca
3
“full blown” NF1. In our opinion she appears to have an
isolated (diffuse) plexiform neurofibroma (and therefore she
would fit the diagnosis of mosaic/segmental NF1)
1
shaped like
an elongated sack hanging from the mandible region down to
the abdomen.
ANTIQUE ILLUSTRATIONS OF OTHER TYPES OF
MOSAICISM IN NEUROFIBROMATOSIS TYPE 1
Other forms of mosaicism in NF1 can be traced in the portraits
of “Buffon’s girl” of 1749 (fig 5)
613
and the “Wart Man” of
Tilesius (fig 6).
14
In both cases we are confronted by reproduc-
tions of severe generalised NF1 phenotypes.
The drawings of the child (fig 5) are by B de Bakker and
appeared in Buffon’s (1707-1788) “Histoire Naturelle” (“Natural
History”).
13
Comte Georges Louis Leclerc de Buffon (1707-
1788) was a naturalist whose work laid the foundations for
advances in the natural sciences in the following centuries.
Ten years after becoming the curator of the King’s garden in
France, he began publishing his 38 volumes which appeared
from 1749 to 1788 and were completed posthumously by a
further eight volumes edited and printed in 1804 by his
assistants.
34
In a hand painted reproduction of the first Italian
edition of the “Histoire Naturelle” (Livorno, 1830), the little girl
is represented naked, front and back view (fig 5), showing
different types of cutaneous anomalies: (1) multiple, dark, leaf
shaped areas of hyperpigmentation on the limbs and (to a
lesser extent) the trunk; (2) a large, raised lesion with the
appearance of “pigskin” encircling the trunk. The anomalies
of pigmentation could be compatible with café au lait spots
(even though somewhat too raised rather than flat) and the
“life jacket” shaped lesions with a diffuse cutaneous plexiform
neurofibroma.
The case described in 1793 by W G Tilesius was referred as
the “Wart Man”.
14
This patient, Johan Gottfried Rheinhard,
was reported under the title “Case History of Extraordinary
Unsightly Skin” and was described as having “countless
growths [fibrous tumours] on the skin, café au lait spots,
macrocephaly, and scoliosis” (fig 6). In a colour reproduction
of the original illustration accompanying the case presenta-
tion, one can see a fleshy m ass hanging forwards towards the
abdomen (fig 6), which might be a pedunculate diffuse cuta-
neous plexiform neurofibroma.
According to the Happle classification of segmental
manifestations of autosomal dominant diseases,
2
these plexi-
for m neurofibromas of Buffon’s girl and the “Wart Man” (figs
Figure 5 Buffon’s girl as painted in the first Italian version (Livorno, 1830) of the “
Histoire Naturelle
” (1749). Personal collection, Marco
Giovannini, Paris.
Figure 6 The “Wart Man”, Johann Gottfried Rheinhard, as
reported by Tilesius von Tilenau, 1793. Authors’ personal collection.
230 Letter
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5 and 6) could fulfil the clinical criteria for type 2 segmental
involvement in NF1 (for example, severe localised manifesta-
tions of the disease superimposed on a non-segmental,
heterozygous manifestation of the same trait). Taking the
description of type 2 mosaicism further, one could speculate
that both lesions may reflect loss of heterozygosity for the NF1
gene that occurred at early developmental stages .
7 19 28–30
ALTERNATIVE DIAGNOSES FOR ALDROVANDI’S
“HOMUNCIO” AND “BUFFON’S GIRL”
Alter native explanations for Aldrovandi’s and Buffon’s cases
could be Proteus syndrome
31
and phacomatosis
pigmentokeratotica,
32
respectively. Both these conditions have
been explained by autosomal lethal mutations surviving by
mosaicism. The underlying autosomal gene is supposed to
exert a lethal effect when present in a zygote; the embryo can
only survive when the mutant cells are growing in close prox-
imity to normal tissue, that is, in a mosaic state.
33 34
According to Proteus syndrome diagnostic criteria,
31
the
Indian “Homuncio” of Aldrovandi could have (fig 1): (1) large
connective tissue naevi (or a single large naevus) (if one con-
siders the mass to be composed of connective tissue); (2) dis-
proportionate overgrowth of one limb; (3) disproportionate
overgrowth of one digit (macrodactyly); and (4) a long face.
These findings could explain the multiple distribution of
mosaic lesions in different areas of the body in the same
person.
23 31 35
Also, the warmness and redness of part of the
mass, reported in Aldrovandi’s Latin text (fig 2), could suggest
an accompanying capillary malformation within the mass, an
additional diagnostic criteria for Proteus syndrome.
31
The trunk lesions of the girl drawn in Buffon’s encyclopae-
dia (fig 5) could be interpreted as a co-occurrence of speckled
lentiginous naevi (the smaller lesions) and/or organoid naevi
with sebaceous differentiation (either the macular lesions or
the large raised lesion or both) arranged according to
Blaschko’s lines and distributed in a checkerboard pattern.
232
We are less in favour of the latter hypotheses because the
clinical appearance of the fleshy (fig 1) and flat (fig 5) masses
are more similar to the variants of plexiform neurofibroma
rather than to the naevi in Proteus syndrome and phacomato-
sis pigmentokeratotica, respectively.
However, regardless of the diagnostic hypotheses, and rely-
ing on the accuracy with which the ancient observers have
depicted their cases, these antique illustrations may be
considered as remarkable and early examples of mosaicism.
ACKNOWLEDGEMENTS
The authors are grateful to Dr Marco Giovannini (Paris) for
permission to use the original illustration in his personal collection
(fig 5); to Sabrina Corsino (CNR, Catania) for her technical and
librarian assistance; to Professor Lorenzo Pavone (Catania), Drs Anto-
nio Tagarelli (Cosenza) and Pierre Wolkenstein (Paris), and to Mr
Peter Bellermann (National Neurofibromatosis Foundation, New
York) for encouragement; to Meena Upadhyaya (Cardiff) for critical
review of the manuscript and for suggestions. S Karger AG (Basel)
and the University Library in Bologna are acknowledged for their per-
mission to reproduce the original illustrations in figs 1 to 4. M
Ruggieri acknowledges Mrs Palmina Giannini, President, Committee
“Paolo Balestrazzi per la lotta alla neurofibromatosi” for funding this
research (V Prize “Paolo Balestrazzi”).
.....................
Authors’ affiliations
M Ruggieri, Institute of Neurological Sciences (ISN), Italian National
Research Council (CNR), Section of Catania, Italy
M Ruggieri, A Polizzi , Department of Paediatrics, University of Catania,
Italy
Correspondence to: Dr M Ruggieri, ISN, Italian National Research
Council (CNR), Viale Regina Margherita 6, 95125 Catania, Italy;
ruggieri@area.ct.cnr.it
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1987;16:899-906.
Letter 231
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