Nasopalpebral Lipoma-Coloboma syndrome: Clinical, radiological, and histopathological description of a novel sporadic case

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  • 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-Garca,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, widows

    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-Garca J, Zenteno JC. 2013.

    Nasopalpebral lipoma-coloboma syndrome:

    Clinical, radiological, and histopathological

    description of a novel sporadic case.

    Am J Med Genet Part A 9999:15.

    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: jczenteno@institutodeoftalmologia.org

    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 probands 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,

    widowspeak, 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 widows 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. 2AC). 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

    ma