Multiple pilomatricomas in twins with Rubinstein-Taybi syndrome

Multiple pilomatricomas in twins with Rubinstein-Taybi syndromeMultiple pilomatricomas in twins with Rubinstein-Taybi syndrome,
Ana Laura Andrade Bueno a,b, Maria Emilia Vieira de Souza a,b, Carla Graziadio b,c, Ana Elisa Kiszewski a,b,d,∗
a Dermatology Service, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil b Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil c Discipline of Clinical Genetics, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil d Pediatric Dermatology Unit, Dermatology Service, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
Received 14 December 2019; accepted 5 March 2020 Available online 15 July 2020
KEYWORDS Pilomatrixoma; Pilomatricoma; Rubinstein-Taybi syndrome; Tumor of the skin appendages
Abstract Pilomatricomas are benign tumors originating from the capillary matrix, which may present as solitary lesions or, less commonly, multiple. Myotonic dystrophy and familial adeno- matous polyposis are the most frequently associated disorders with multiple pilomatricomas. There are few reports relating these tumors to other genetic syndromes. Rubinstein-Taybi syn- drome is a rare autosomal dominant disorder characterized by intellectual disability and typical dysmorphic characteristics. There are five case reports relating to multiple pilomatricoma to Rubinstein-Taybi syndrome, an association that needs to be clarified. For this reason, we report the first case of multiple pilomatricoma in monozygotic twins with typical Rubinstein-Taybi
syndrome. © 2020 Sociedade Brasileira de Dermatologia. Published by Elsevier Espana, S.L.U. This is an
he CC
open access article under t
How to cite this article: Bueno ALA, Souza MEV, Graziadio C, Kiszewski AE. Multiple pilomatricomas in twins with Rubinstein- Taybi syndrome. An Bras Dermatol. 2020;95:619---22.
Study conducted at the Dermatology Service, Universidade Federal de Ciências da Saúde de Porto Alegre and Pediatric Derma- tology Unit, Hospital da Crianca Santo Antonio, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil.
∗ Corresponding author. E-mail: [email protected] (A.E. Kiszewski).
I
https://doi.org/10.1016/j.abd.2020.03.011 0365-0596/© 2020 Sociedade Brasileira de Dermatologia. Published by E BY license (http://creativecommons.org/licenses/by/4.0/).
BY license (http://creativecommons.org/licenses/by/4.0/).
ntroduction
ilomatricomas are uncommon benign tumors derived from air matrix. They mainly affect the pediatric population and re more frequently located on the head and neck. They resent clinically as nodules with firm or stony consistency, ircumscribed, normochromic, or erythematous, which can e confused with epidermal cysts. Although they usually
resent as solitary lesions, multiple pilomatricomas can be bserved in 2.4% to 5% of cases.1---3
lsevier Espana, S.L.U. This is an open access article under the CC
a p f m t s
d g i B i s m a m b
m i
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M c m n s o r h l f t a r n i
n r a s s p s t o n p w w t
Figure 1 Twin 1 with slanting eyelid slits, discrete microg- nathia, prominent auricular helices, nipple hypertelorism, s t
D
20
Multiple pilomatricomas can be sporadic, familial, or ssociated with an underlying syndrome. Myotonic dystro- hy and familial adenomatous polyposis (FAP) are the most requently associated disorders with multiple pilomatrico- as. There are sporadic reports of the association of these
umors with Turner, Kabuki, Sotos, and Rubinstein-Taybi yndromes.2
Rubinstein-Taybi Syndrome (RTS) is a rare autosomal ominant genetic disorder, characterized by postnatal rowth retardation, moderate to severe intellectual disabil- ty, and a wide range of typical dysmorphic characteristics. road, angled thumbs and halluces are a distinguish-
ng feature of the syndrome. Facial anomalies include lanted eyelid slits, high and elongated nasal pyramid, and icrognathia. Cardiac malformations, dental alterations,
nd cryptorchidism are common.4 The most common der- atological findings include hemangiomas, hypertrichosis, rachyonychia, and a tendency to keloid formation.1
Although approximately 60% of cases are associated with utations in the CREBBP or EP300 genes, the etiology of RTS
s heterogeneous and poorly defined.1,5
There are few cases describing the association of pilo- atricomas with RTS, and it is not clear whether this
ssociation is due to chance.6 According to a recent review f the literature, nine cases have been reported thus far, nd five of them presented multiple lesions.2 The authors eport the first case of multiple pilomatricomas in monozy- otic twins with typical RTS.
ase reports
onozygotic twins, 8 years old, with delayed neuropsy- homotor development, oblique eyelid clefts, discrete icrognathia, ogival palate, prominent auricular helix,
ipple hypertelorism, and mild hypertrichosis on the dor- al spine and shoulders. Both had a previous history f cryptorchidism and of short, wide thumbs, whose adial deviation had been surgically corrected. Twin 1 ad undergone cardiac surgery to correct interventricu- ar communication and had a previous history of occipital, rontal, and supramammary hemangiomas, which had spon- aneously regressed (Fig. 1). Twin 2 presented cerebral queduct stenosis and polydactyly, also previously cor- ected. The karyotype examination of both patients was ormal (46, XY) and, in light of the typical phenotypic find- ngs, they were diagnosed with RTS by the genetics team.
At a dermatological consultation, twin 1 presented a ormal, asymptomatic nodular lesion in the left scapular egion. An ultrasonography was performed, which showed n echogenic nodular image, emitting a posterior acoustic hadow, measuring 1.4 cm in its largest diameter. In sub- equent consultations, over a period of two years, both atients developed multiple similar nodular lesions on the calp (total of five lesions in twin 1 and four in twin 2). Two of hem were excised, one located on the scalp and the other n the scapular region (Fig. 2), both showing histologically a odular proliferation composed of basaloid matrix cells and
hantom cells (Figs. 3 and 4), findings that were compatible ith the diagnosis of pilomatricomas. The remaining lesions ere clinically followed-up. The patients had no family his-
ory of pilomatricomas.
r b a
ternal scar secondary to cardiac surgery to correct interven- ricular communication, wide thumbs and radial deviation.
iscussion
ilomatricomas are usually benign solitary lesions. However, hese tumors can present as multiple lesions and, although hey can occur in healthy individuals, it is recommended o collect a detailed family history and discard associated yndromes.7
Myotonic dystrophy and FAP are the syndromes most
elated to multiple pilomatricomas. The association etween RTS and pilomatricomas was first published in 19946
nd, since then, eight more cases have been described.
Multiple pilomatricomas in Rubinstein-Taybi syndrome 621
Figure 2 Normochromic nodular lesion in the left scapular region which was excised. Mild hypertrichosis on the dorsal spine and shoulders.
Figure 4 Anatomopathological aspect: nodular proliferation composed of basaloid matrix cells and ghost cells (Hematoxylin &
u t t 2 w c m F t w l
c b h D t l m H t i C m
c o t l s
a a I s
Figure 3 Anatomopathological aspect: nodular proliferation composed of basaloid matrix cells and ghost cells (Hematoxylin & eosin, ×10).
However, only five of these cases related multiple piloma- tricomas to the syndrome.2
A 2019 review of the syndromes associated with multiple pilomatricomas found that non-syndromic patients tend to have fewer pilomatricomas when compared with syndromic
patients.2 While 4.5% of non-syndromic individuals devel- oped more than five pilomatricomas, 46.3% of syndromic patients developed six or more tumors. However, although the relationship between multiple pilomatricomas and the
F
N
eosin, ×40).
nderlying syndrome strengthens as the number of piloma- ricomas increases, some syndromes may have only one or wo lesions.2 The review of the RTS cases described until 019 showed that the number of pilomatricomas associated ith this syndrome is quite varied. From a total of nine ases, four cases had two to five pilomatricomas, one had ore than 10 and four had solitary pilomatricomas.1,2,5,6,8---10
urthermore, a series of four cases published in 1998 showed hat, in this group of patients, the mean age of tumor onset as not earlier than in healthy patients, in whom most
esions appear between the ages of 8 months and 10 years.9
The etiology of pilomatricoma in RTS has yet to be elu- idated. Mutations in two genes, CREBBP and EP300, have een observed in affected individuals and both encode omologous proteins that act as transcription co-activators. uring organogenesis, CREBBP is expressed in specific cell ypes of the developing heart, vasculature, skin, lungs, and iver. In 2016, the first case of RTS with multiple pilomatrico- as diagnosed by CREBBP mutation analysis was reported. owever, the correlation between the CREBBP genotype and he onset of multiple pilomatricomas still needs to be clar- fied, since there are also case reports that describe the REBBP mutation in patients with RTS without pilomatrico- as or with a solitary lesion.5
Data on pilomatricomas in RTS are still limited to some ase reports. In the literature review. This is the first report f multiple pilomatricomas in twins with RTS, reinforcing he association between these two entities. The molecu- ar mechanisms that lead patients with RTS to a greater usceptibility to pilomatricomas warrants further studies.
In some cases, the detection of pilomatricomas may offer n opportunity for the diagnosis of RTS. The therapeutic pproach to multiple lesions in RTS is yet to be established. n the patients presented, a conservative approach was cho- en, and they are being followed-up without intervention.
inancial support
one declared.
s s a t c m
m t i e t l
m t i e t l
C
uthors’ contributions
na Laura Andrade Bueno: Approval of the final ver- ion of the manuscript; conception and planning of the tudy; elaboration and writing of the manuscript; obtaining, nalyzing, and interpreting the data; effective participa- ion in research orientation; intellectual participation in ropaedeutic and/or therapeutic conduct of studied cases; ritical review of the literature; critical review of the anuscript. Maria Emilia Vieira de Souza: Approval of the final ver-
ion of the manuscript; conception and planning of the tudy; elaboration and writing of the manuscript; obtaining, nalyzing, and interpreting the data; intellectual participa- ion in propaedeutic and/or therapeutic conduct of studied ases; critical review of the literature; critical review of the anuscript. Carla Graziadio: Approval of the final version of the
anuscript; conception and planning of the study; elabora- ion and writing of the manuscript; obtaining, analyzing, and nterpreting the data; effective participation in research ori- ntation; intellectual participation in propaedeutic and/or herapeutic conduct of studied cases; critical review of the iterature; critical review of the manuscript.
Ana Elisa Kiszewski: Approval of the final version of the anuscript; conception and planning of the study; elabora-
ion and writing of the manuscript; obtaining, analyzing, and nterpreting the data; effective participation in research ori- ntation; intellectual participation in propaedeutic and/or herapeutic conduct of studied cases; critical review of the iterature; critical review of the manuscript.
onflicts of interest
na Laura Andrade Bueno, Maria Emilia Vieira de Souza, and arla Graziadio declare to have no conflict of interest. Ana
1
Bueno ALA et al.
lisa Kiszewski declares to have a conflict of interest with he company Johnson & Johnson.
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Introduction