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NR 7-9/2007
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Lacrimal caruncle
nevus associated with Rubinstein–Taybi syndrome
Znamię barwnikowe mięska
łzowego u chorego z zespołem Rubinsteina–Taybiego
Arkadiusz Pogrzebielski, Anna Piwowarczyk,
Joanna Kobylarz, Bożena Romanowska-Dixon
From the Department of Ophthalmology and Ocular Oncology,
Jagiellonian University, Krakow, Poland
Head: Bożena Romanowska–Dixon MD |
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| Summary: |
We present a 28-year old
man with diagnosed Rubinstein–Taybi syndrome (RSTS),
known as „Broad thumb – Hallux syndrome” with
co-existing lacrimal caruncle tumor. Because of the
documented enlargement of the lacrimal caruncle mass and
known increased risk to develop malignancies in RSTS
patients we decided to perform excisional biopsy, which
revealed caruncle nevus. To our knowledge this is the
first description of such an association. |
| Słowa kluczowe: |
zespół Rubinsteina–Taybiego,
znamię barwnikowe spojówki, znamię mięska łzowego, zez
rozbieżny, goniodysgeneza, hiperteloryzm. |
| Key words: |
Rubinstein–Taybi syndrome,
conjunctival nevus, lacrimal caruncle nevus, exotropia,
goniodysgenesis, hypertelorism. |
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The Rubinstein–Taybi syndrome (RSTS)
known also as „Broad thumb – Hallux syndrome” is a well known
mental retardation syndrome associated with multiple congenital
anomalies. It was first described by Rubinstein and Taybi in
1963 (1).
The incidence of the syndrome is estimated to be 1:100 000
newborns (2). The molecular genetic studies showed that RSTS is
in part caused by microdeletions at chromosome 16p13.3 or
mutations of CREB-binding protein (CREBBP), a nuclear protein
participating as a co-activator in cAMP-regulated gene
expression (3,4). We present a patient with RSTS and an
enlarging lacrimal caruncle nevus. The patient and his parents
gave the informed consent to participate in the study.
Case report
28-year old Caucasian male with diagnosed RSTS presented in
January 2006 at the Department of Ophthalmology and Ocular
Oncology of Jagiellonian University in Krakow with an enlarging,
brownish-reddish mass in lacrimal caruncle in his left eye (Fig.
1a) noted by his parents 6 months ago. The family history
regarding RSTS or malignancies was negative. Snellen visual
acuity (VA) test results were not fully adequate because of
patient’s mental retardation and aphasia. In preferential
looking test (Teller Acuity Charts, Richmond Products Inc., USA)
the right eye (RE) VA was 4.8 cy/cm (Snellen equivalent 0.2) and
the left eye (LE) VA was 6.5 cy/cm (Snellen equivalent 0.3). The
patient did not present any color vision disturbances in „Color
Vision Testing Made Easy” by Terrace L. Waggoner (Bernell Corp.,
USA). The direct and consensual pupil reactions were normal and
anisocoria was visible – the pupil diameter in the RE was 2 mm
bigger than in the LE. The patient showed diminished growth,
broad and medially deviated thumbs, (Fig. 1b) big toes,
posterior rotated ears, hypertelorism, antimongoloid slant of
the palpebral fissures, beaked nose, (Fig. 1c, Fig. 1d)
high-arched palate, and dental abnormalities. We diagnosed
alternating exotropia 9∆, V-syndrome, and lack of convergence.
Slit-lamp examination showed in LE a pigmented lacrimal caruncle
tumor, which measured 7 mm in diameter and 1 mm in thickness,
ocular melanosis in both eyes and partial iris atrophy.
Gonioscopy disclosed mild signs of goniodysgenesis in form of
hypoplasia of peripheral part of iris, basal iris processes
associated with delicate membranaceous structures and marked
angle hyperpigmentation, especially in RE. The intraocular
pressure was 18 mmHg in RE and 17 mmHg in LE. The refractive
error after cycloplegia was in RE -0.25 sphD +1.25 cyl D ax 43
and in LE + 0.75 cyl D ax 154. Axial length measured in RE was
23.36 mm and in LE 22.76 mm. Funduscopy revealed normal optic
nerve head and mild macular abnormalities in form of absent
foveal reflex and unusual distribution of pigment (Fig 1e). The
fluorescein angiography showed corresponding window defects in
both macular regions (Fig 1f). The performed Jones test and
irrigation of lacrimal drainage system did not reveal any sings
of stenosis. Because of the documented, worrisome for the
patient’s parents enlargement of the lacrimal caruncle mass and
known increased risk to develop malignancies in RSTS patients we
decided to perform excisional biopsy in general anesthesia. The
histopathology revealed a pigmented nevus of lacrimal caruncle.
Discussion
RSTS is a rare genetically determined disease (3) Petrij et al.
showed that the breakpoints at chromosome 16p13.3 are all
restricted to a region that contains CREBBP (4). Genetic
heterogeneity in RSTS is shown by the demonstration of mutations
in the EP300 gene as a cause of the disease. (OMIM Online
Mendelian Inheritance in Man #180849) The variety of different
abnormalities (including ocular) is undoubtedly caused by
disfunction of mutated CREBBP (5) or chromosomal lesions
mentioned above.
The ocular findings in RSTS include among others hypertelorism,
antimongoloid slant of the palpebral fissures, epicanthal folds,
ptosis, congenital obstruction of the lacrimal drainage system,
strabismus, latent nystagmus, ametropia, macrocornea,
microphthalmos, iris and optic nerve head colobomas, congenital
cataract and glaucoma, optic nerve atrophy and retinal changes
(5,6). Van Genderen et al. analyzed 24 patients with ocular
abnormalities in RSTS patients and found strabismus in 67%
(17/24), high myopia in 25% (6/24), lacrimal duct abnormalities
in 25% (6/24) patients, congenital or presenile cataract in 25%
(6/24), retinal abnormalities in 75% (18/24), and in few cases
congenital glaucoma and colobomata (5). The lacrimal duct
abnormalities are very common in RSTS patients (7,8) van
Genderen et al. found nasolacrimal duct obstruction in 25% of
patients (5). Rubinstein et al. described it in 37% of patients
(9). However our patient did not show any abnormalities of the
lacrimal drainage system (6). Our patient had alternating
exotropia, similarly to the findings of van Genderen et al. who
found this abnormality in 15 among 17 patients with RSTS and
strabismus (5). Rubinstein et al. published results of the
analysis of 571 patients with RSTS and discovered different
forms of strabismus in 71% of patients, and refractive errors in
56% of patients (9). |
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Congenital cataract or congenital
glaucoma is common in RTST patients. Our patient did not
demonstrate them; however he had mild degree goniodysgenesis.
Besides signs of goniodysgenesis described above we did not find
other signs described by Wajda et. al. like irregular Schwalbe’s
line, invisible Schlemm’s channel, hypoplastic scleral spur, or
abnormal vessels in the angle (7,10). Some authors describe
unilateral ptosis in RSTS patients, which we did not notice in
our case (11). Van Genderen et al. describe macular
abnormalities in 75% of patients in their series with RSTS (5).
In our case we were able not only to observe them during
funduscopy, but also to see window defects in macular region
during fluorescein angiography.
Miller and Rubinstein noted that patients with RSTS have an
increased risk of malignant and benign tumors formation,
especially in the nervous system (12). These authors analyzed
over 700 patients with RSTS and found 17 with malignant tumors
and 19 with benign tumors. Twelve of 36 tumors were located in
the nervous system and included meningioma, oligodendroglioma,
medulloblastoma, and neuroblastoma. Other tumor types included
rhabdomyosarcoma and leukemias (12). Sammartino et al. describe
spontaneous formation of multiple keloids in patient with RSTS
(11). Petrij et al. suggested that the unusual incidence of
neoplasms in RSTS, as well as propensity to form keloids, may be
explained by the role proposed for CREBBP in cAMP-regulated cell
immortalization. (OMIM) Our patient had a benign pigmented nevus
of lacrimal caruncle. Schepis et al. described RSTS patient with
epidermal nevus (13). To our knowledge it is the first report of
an association of RSTS and lacrimal caruncle nevus.
REFERENCES:
1. Rubinstein JH, Taybi H: Broad thumbs and toes and facial
abnormalities. A possible mental retardation syndrome. Am J Dis
Child 1963, 105, 588-608.
2. Hennekam RC, Stevens CA, Van de Kamp JJ: Etiology and
recurrence risk in Rubinstein-Taybi syndrome. Am J Med Genet
Suppl 1990, 6, 56-64.
3. Breuning MH, Dauwerse HG, Fugazza G, Saris JJ, Spruit L,
Wijnen H, Tommerup N, van der Hagen CB, Imaizumi K, Kuroki Y, et
al.: Rubinstein-Taybi syndrome caused by submicroscopic
deletions within 16p13.3. Am J Hum Genet 1993, 52, 249-254.
4. Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC,
Masuno M, Tommerup N, van Ommen GJ, Goodman RH, Peters DJ, et
al.: Rubinstein-Taybi syndrome caused by mutations in the
transcriptional co-activator CBP. Nature 1995, 376, 348-351.
5. van Genderen MM, Kinds GF, Riemslag FC, Hennekam RC: Ocular
features in Rubinstein-Taybi syndrome: investigation of 24
patients and review of the literature. Br J Ophthalmol 2000, 84,
1177-1184.
6. Marabotti A, Giannecchini G, Cariello A, Cappelli C,
Giannecchini I, Bedei A: Stenosis of the lachrymal system in
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7. Quaranta L, Quaranta CA: Congenital glaucoma associated with
Rubinstein-Taybi syndrome. Acta Ophthalmol Scand 1998, 76,
112-113.
8. Roy FH, Summitt RL, Hiatt RL, Hughes JG: Ocular
manifestations of the Rubinstein-Taybi syndrome. Case report and
review of the literature. Arch Ophthalmol 1968, 79, 272-278.
9. Rubinstein JH: Broad thumb-hallux (Rubinstein-Taybi) syndrome
1957-1988. Am J Med Genet Suppl 1990, 6, 3-16.
10. Wajda M, Turno-Krecicka A: Goniodysgenesis associated with
Rubinstein-Taybi syndrome. Klin Oczna 2000, 102, 139-141.
11. Sammartino A, Cerbella R, Lembo G, Federico A, Loffredo L:
Rubinstein-Taybi syndrome with multiple keloids. J Fr Ophtalmol
1986, 9, 725-729.
12. Miller RW, Rubinstein JH: Tumors in Rubinstein-Taybi
syndrome. Am J Med Genet 1995, 56, 112-115.
13. Schepis C, Greco D, Siragusa M, Batolo D, Romano C:
Rubinstein-Taybi syndrome with epidermal nevus: a case report.
Pediatr Dermatol 2001, 18, 34-37.
Support provided by the Malopolska Foundation
for Saving the Sight, Krakow, Poland.
Praca wpłynęła do Redakcji 20.04.2006 r. (888)
Zakwalifikowano do druku 05.07.2007 r.Adres do
korespondencji (reprint requests to):
Arkadiusz Pogrzebielski MD
Department of Ophthalmology and Ocular Oncology
Jagiellonian University
Kopernika Str. 38
31-501 Kraków
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