CLINICAL REPORT
Nasopalpebral Lipoma-Coloboma Syndrome:Clinical, Radiological, and HistopathologicalDescription of a Novel Sporadic CaseOscar F. Chacon-Camacho,1 Monica S. Lopez-Martinez,2 Johanna Vazquez,3
Angel Nava-Castaneda,4 Fernando Martin-Biasotti,5 Raul E. Pina-Aguilar,2
Marisol Iniguez-Soto,4 Job Acosta-Garcıa,5 and Juan C. Zenteno1,6*1Department of Genetics, Institute of Ophthalmology “Conde de Valenciana,”, Mexico City, Mexico2Department of Genetics, Centro Medico Nacional “20 de Noviembre,” ISSSTE, Mexico City, Mexico3Departamento de Estomatologia Pediatrica, Hospital de Especialidades Pediatricas, Tuxtla Gutierrez-Chiapas, Mexico4Department of Oculoplastics, Institute of Ophthalmology “Conde de Valenciana,”, Mexico City, Mexico5Department of Radiology and Imaging, Institute of Ophthalmology “Conde de Valenciana,”, Mexico City, Mexico6Faculty of Medicine, Department of Biochemistry, National Autonomous University of Mexico (UNAM), Mexico City, Mexico
Manuscript Received: 11 December 2012; Manuscript Accepted: 1 February 2013
Nasopalpebral lipoma-coloboma syndrome is an extremely un-
common autosomal dominant condition characterized by con-
genital upper eyelid and nasopalpebral lipomas, colobomata of
upper and lower eyelids, telecanthus, and maxillary hypoplasia.
A few familial and sporadic cases of thismalformation syndrome
have been previously reported. Here, the clinical, radiological,
and histopathological features of a sporadic Mexican patient
with the nasopalpebral lipoma-coloboma syndrome are de-
scribed. To our knowledge, this is the first time that craniofacial
3D computed tomography imaging was used for a detailed
assessment of the facial lipoma. � 2013 Wiley Periodicals, Inc.
Key words: nasopalpebral lipoma-coloboma syndrome; lipoma;
craniofacial syndrome; telechantus; hamartoma
INTRODUCTION
Nasopalpebral lipoma-coloboma syndrome (OMIM%167730) is
an extremely uncommon autosomal dominant disease character-
ized by bilateral congenital nasopalpebral lipomas, bilateral
upper and lower eyelid colobomata, broad forehead, widow’s
peak, flaring of medial eyebrows, telecanthus, and maxillary hypo-
plasia [Penchaszadeh et al., 1982]. Additional features may include
displacedor aplastic lacrimal punctae, persistent epiphora, aberrant
eyelashes, conjunctival hyperemia, corneal and lens opacities, and
divergent strabismus [Penchaszadeh et al., 1982]. This rare syn-
dromewas first described byPenchaszadeh et al. [1982], and to date
only two familial and three sporadic cases have been reported
[Penchaszadeh et al., 1982; Akarsu and Sayli, 1991; Bock-Kunz
et al., 2000;Moreira Gonzalez and Jackson, 2003; Babu et al., 2011].
The etiology is unknown, but it has been hypothesized that a
migration defect of the neural crest cells causes abnormal develop-
ment of the craniofacial anatomy. In this work, the clinical,
radiological, and histopathological features of an additional case
of nasopalpebral lipoma-coloboma syndrome are reported.
CLINICAL REPORT
A 2-month-old Mexican female was referred to our hospital due to
bilateral congenital eyelid malformation. She was the sixth child of
nonconsanguineous and unaffected parents. Hermother was 29 and
How to Cite this Article:Chacon-Camacho OF, Lopez-Martinez MS,
Vazquez J, Nava-Castaneda A, Martin-
Biasotti F, Pina-Aguilar RE, Iniguez-Soto
M, Acosta-Garcıa J, Zenteno JC. 2013.
Nasopalpebral lipoma-coloboma syndrome:
Clinical, radiological, and histopathological
description of a novel sporadic case.
Am J Med Genet Part A 9999:1–5.
Oscar F. Chacon-Camacho and Monica S. Lopez-Martinez contributed
equally to the conduct of this research and are to be considered first
authors.�Correspondence to:
Dr. Juan C. Zenteno, Research Unit, Institute of Ophthalmology,
“Conde de Valenciana,” Chimalpopoca 14, Col. Obrera, Mexico City,
CP 06800, Mexico. E-mail: [email protected]
Article first published online in Wiley Online Library
(wileyonlinelibrary.com): 00 Month 2013
DOI 10.1002/ajmg.a.35916
� 2013 Wiley Periodicals, Inc. 1
her father 30 years old when she was born. Her family history was
uneventful and all siblings were healthy. The proband’s mother
received regular prenatal care and denied exposure to potentially
teratogenic agents. The patient was born via spontaneous vaginal
delivery andherbirth lengthwas51 cm(75thcentile),weight 3,050 g
(50th centile), andhad anApgar score of 9/9; noothermeasurements
were documented. Several facial abnormalities were apparent at
birth. Physical examination was performed at 2 months of age
(Fig. 1A), when she was 52 cm long (3rd centile), weighed 3,800 g
(3rd centile) and had a head circumference of 37 cm (25th
centile). At seven months (Fig. 1B), her length was 59 cm (below
3rd centile), weight 5,800 g (below 3rd centile) andOFC 41 cm (3rd
centile). Delayed physical development may have been related to
chronic malnutrition and recurrent respiratory tract infections.
Examination disclosed bilateral symmetrical accumulation of sub-
cutaneous tissue in the nasopalpebral region, extending to the
forehead and upper lip (Fig. 1A,B). This tumor was round, soft,
and displaced the inner canthi laterally causing marked telecanthus
(Fig. 1A,B). Symmetrical colobomataofupper and lower lids, located
at the junction of the inner andmiddle thirds of lids (Fig. 1C), as well
asabsenceordisplacementofupperand lower lacrimalpunctae,were
seen.Absenceof themedial eyelashes (Fig. 1C) andbilateral epiphora
were evident. In addition, she had dolicocephaly, broad forehead,
widow’speak, sparseandmaldirectedeyebrows,broadanddepressed
nasalbridge, and low-set, cuppedanddysplastic ears (Fig. 1D).Atage
7months the forehead and nasopalpebral tumors weremore promi-
nent, circumscribed to the same anatomic regions, and covering the
medial segment of the irises (Fig. 1B). Physical examination identi-
fied bilateral clinodactyly of fifth finger, but no other systemic
anomalies.
Karyotype analysis using GTG-banding was normal female (46,
XX in 30 cells). Eye ultrasound was performed at 7 months of age
demonstrating a short anteroposterior length: 18.3 mm in right
eye and 18.7 mm in left, classified as bilateral nanophthalmos
FIG. 1. Facial appearance of the patient at 2 (A) and 7 (B) months of age. A,B: Frontal view demonstrating a nasopalpebral tumor expanding
to the frontal and upper lip regions. Bilateral symmetrical upper and lower eyelid colobomata, broad forehead widow’s peak, flaring of medial
eyebrows, telecanthus were also observed. C: Bilateral symmetrical upper and lower colobomata at the junction of the inner and middle thirds,
absence of eyelashes lateral to the eyelid cleft, and telecanthus are evident on the right side. D: Right ear dysplasia with overturned helix,
crumpled ear and prominent helical root (“railroad track” ear).
2 AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(average axial length for age: 20.1 mm) [Frazier and Green, 2002].
Computed axial and coronal tomography (CT) demonstrated no
brain malformation and confirmed the hypodense subcutaneous
tumor involving the forehead and nasal bridge, suggestive of
lipomatous tissue (Fig. 2A–C). CT with three-dimensional recon-
struction of facial bones and soft tissues showed lipomatous tissue
covering the forehead and nasopalpebral regions (Fig. 2D,E) as
well as maxillary hypoplasia and normal interorbital distance
(15 mm; Fig. 2F). A biopsy of forehead skin and subcutaneous
tissue was compatible with hamartoma of smooth muscle, mixed
with lipomatous tissue (Fig. 3A,B). Clinical findings in our patient
were compared with those in previously reported cases (Table I).
FIG. 2. Image studies. A: Computed axial tomographic scan of patient showing a hypodense lesion (white arrow) between the nasal bones
and the maxillar edge, and the globes. B: Computed axial tomographic axial scan showing well-defined hypodense tissue (white arrow) on
the superficial frontal region. C: Computed coronal tomographic image demonstrates increased tumor tissue (white arrow) on the lateral
superficial edge of the nasal region. D,E: Frontal and lateral views of computed tomography with three-dimensional reconstruction of facial
soft tissues showing abnormal lipomatous tissue on the fronto-nasal region. F: Computed tomography with three-dimensional reconstruction
of facial bones showing normal interorbital distance (15 mm) and maxillar hypoplasia.
FIG. 3. Histopathological analysis of forehead tumor biopsy showing smooth muscle tissue (white arrow) combined with lipomatous tissue
(black arrow). A: H&E 10�; B: H&E 40�.
CHACON-CAMACHO ET AL. 3
� 2013 Wiley Periodicals, Inc. 3
DISCUSSION
Nasopalpebral lipoma-coloboma syndrome is an extremely un-
common cranio-facial disorder reported in a few familial and
sporadic cases [Penchaszadeh et al., 1982; Akarsu and Sayli,
1991; Bock-Kunz et al., 2000; Moreira Gonzalez and Jackson,
2003; Babu et al., 2011]. The first description was by Penchaszadeh
et al. [1982], who studied a Venezuelan family with eight affected
individuals. In this pedigree, vertical and male-to-male transmis-
sion suggested autosomal dominant inheritance. Complete
penetrance was observed, although mild clinical variability in
malformations of the lacrimal punctae, corneal opacities and
strabismus occurred [Penchaszadeh et al., 1982] (Table I). Akarsu
and Sayli [1991] reported a family with seven affected individuals
over three generations. Interestingly, the propositus also showed
variability in his anomalies, such as lacrimal punctae malforma-
tions (the upper being displaced, whereas the lower were normal),
corneal opacities and conjunctival hyperemia (Table I). Midfacial
hypoplasia, listed as a cardinal feature by Penchaszadeh [1982], was
absent in the proband and his affected mother [Akarsu and Sayli,
1991]. To date, only three sporadic cases have been reported (Table
I). Bock-Kunz et al. [2000] described a young affected male who
presented all major clinical features but normal intraorbital bony
distance; mild maxillary hypoplasia, and lipomatous tissue on the
forehead and nasal bridge were demonstrated by CT. In the patient
reported here, CT scan demonstrated that the hypodense lesion in
the nasopalpebral and forehead region is composed of lipomatous
tissue. Moreover, a normal interorbital distance and presence of
lipomatous tissue were confirmed on three-dimensional CT recon-
struction of facial bones and soft tissues. To our knowledge, this
imaging technique has not been applied previously to patients with
nasopalpebral lipoma-coloboma syndrome. In 2003, Moreira et al.
reported a Russian boy with all major signs of the syndrome, but
withnormal bony anatomyandnormal intercanthal distance inCT.
Magnetic resonance imaging showed lateral displacement of the
globes due to the midline lipomatous accumulation in the naso-
palpebral area [Moreira et al., 2003]. Recently, Babu et al. [2011]
described a 16-year-old female with features of the syndrome, but
affecting only the right side of the face. This patient also had right
limbal dermoid and right iris coloboma.
TABLE 1. Clinical Characteristics in the Present Patient and Previously Familial and Sporadic Reported Subjects With NasopalpebralLipoma-Coloboma Syndrome
Features
Familial cases (FC)
Findings
frequency (%)
FC1 FC2 Sporadic cases (SC)
IV-1 III-2 II-2 III-8 III-9 III-10 Probanda 1 2 3 4
Age at diagnosis 15 m 32 y 71 y 10 y 6½ y 3½ y 5 y 2 m 1 d 16 m 16 y �Sex Ma Ma Ma Fe Fe Fe Ma Fe Ma Ma Fe �Bilateral symmetrical
nasopalpebral lipomas
þ þ þ þ þ þ þ þ þ þ þ, c 100
Bilateral symmetrical upper and
lower lid colobomas
þ þ þ þ þ þ þ þ þ þ þ, c 100
Broad forehead þ þ þ þ þ þ þ þ NR þ NR 82
Widow’s peak þ þ þ þ þ þ NR þ NR þ NR 73
Outflaring of medial eyebrow þ þ þ þ þ þ NR þ NR þ NR 73
Telecanthus þ þ þ þ þ þ þ þ þ þ NR 91
Maxillary hypoplasia þ þ þ þ þ þ NR þ þ þ NR 82
Malposition of lacrimal punctae þ, L þ, U þ, U þ, U þ, U þ, U þ, U þ, L � NR NR 73
Absence of lacrimal punctae þ, U � þ, L � � � � þ, U þ, U NR NR 37
Persistent epiphora þ þ þ þ þ þ � þ þ þ NR 82
Conjuntival hyperemia þ þ þ þ þ þ � þ NR þ NR 73
Corneal opacities � B B Le Le B � � � � NR 46
Lens opacities � R � � Le � NR � � � NR 18
Divergent strabismus þ þ þ þ þ þ NR � þ � NR 64
Ear dysplasia � � � � � � � þ � � � 9
Clinodactyly � � � � � � � þ � � � 9
Nanophthalmos
(ocular echography finding)
� � � � � � � þ � � � 9
Combined hamartoma
(histopathological finding)
� � � � � � � þ � � � 9
Characteristic:þ, present;�, absent;c, right unilateral lesions; B, bilateral anomaly; d, days; Fe, female; L, lower lids; Le, left anomaly; Ma,male; m,months; NR, not reported; R, right anomaly; U, upper lids;y, years.FC1, Penchaszadeh’s et al. family; FC2, Akarsu and Sayli’s propositus; SC1, Present case; SC2, Bock-Kunz’s et al. patient; SC3,Moreira and Jackson’s patient; SC4, Babu’s et al. patient (this patient had limbaldermoid and iris coloboma in right eye).a<No other affected relatives were described in the original article.
4 AMERICAN JOURNAL OF MEDICAL GENETICS PART A
In the patient described here, two novel clinical findings were
identified. First, ocular echography performed at age 7 months
revealed shorteningof the antero-posterior axial length, leading to a
diagnosis of bilateral nanophthalmos. Second, histopathological
examination of the nasopalpebral mass revealed a hamartoma of
smoothmusclemixedwith lipomatous tissue.Hamartomaspresent
as disorganized but benign mass, composed of cells indigenous to
the particular site [Kumar et al., 2010].
The primary defect leading to the development of the nasopal-
pebral lipoma-coloboma syndrome is unknown. No cytogenetic
abnormality has been demonstrated in these patients and other
genetic studies havenot beenperformed.Penchaszadeh et al. [1982]
proposed a pathogenic mechanism where tumor, coloboma and
other malformations might be due to local morphogenetic inter-
ference from lipomatous hamartomata. They suggested that a
mutant gene in the early phase of embryonic development could
be responsible for the production of the hamartoma of smooth
muscle in this particular region. Hence, a somatic mutation could
interfere with normal facial morphogenesis. Alterations in the
formation, migration, and subsequent development of ectomesen-
chymal neural crest cells have also been postulated as an alternative
pathogenic cause [Penchaszadeh et al., 1982].
Several conditions such as frontonasal dysplasia [Sedano and
Gorlin, 1988], MOTA syndrome [Marles et al., 1992], and fronto-
nasal encephalocele [Jackson et al., 1983] can show overlap with
nasopalpebral lipoma-coloboma syndrome. Characteristics of
these conditions include orbital hypertelorism, cranium bifidum
occultum, bifid nose, and medial cleft lip/palate (frontonasal
dysplasia) and orbital hypertelorism, oculopalpebral synechia,
microphthalmia–anophthalmia, nasal tip groove, anal stenosis
and aberrant anterolateral scalp hairline (MOTA syndrome).
Our patient did not have features suggestive of these disorders.
Considering that the syndrome is associated with facial alter-
ations alone, cosmetic surgery is relevant for the management.
Previously, surgical corrections had satisfactory results in some
patients [Sevin et al., 1991; Moreira Gonzalez and Jackson, 2003].
In conclusion, this is the sixth report of the nasopalpebral
lipoma-coloboma syndrome. Nanophthalmos and hamartoma
of smooth muscle are new features that expand the clinical spec-
trum of the disorder. The application of technologies such as whole
exome or genomic sequencing may shed light to the origin of this
unusual autosomal dominant syndrome.
ACKNOWLEDGMENTS
The authors thank Biol. Concepcion Yerena and Biol. Roberto
Guevara for chromosome analysis.
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