Nasopalpebral Lipoma-Coloboma Syndrome
Description
Nasopalpebral lipoma-coloboma syndrome (NPLCS) is an autosomal dominant condition characterized by upper eyelid and nasopalpebral lipomas, colobomas of upper and lower eyelids, telecanthus, and maxillary hypoplasia (summary by Suresh et al., 2011).
Clinical FeaturesPenchaszadeh et al. (1980, 1982) described a Venezuelan family in which 8 persons in 3 generations showed bilateral coloboma of the upper and lower lids at the junction between their middle and inner thirds; prominent circumscribed, rounded deposits of fat in the medial region of both upper lids; aplasia or malposition of the lacrimal puncta; ocular hypertelorism; broad nasal bridge and fatty accumulations on the nasal bridge and nasolabial areas. Male-to-male transmission was observed. Penetrance appeared to be complete. One affected male in the second generation had affected children by each of 2 wives and only normal children by a third.
This syndrome was validated by the Turkish family reported by Akarsu and Sayli (1991) in which 7 members in 4 generations were affected. Features included congenital nasopalpebral lipoma, telecanthus, and bilateral colobomas of upper and lower lids without midface hypoplasia. The family contained 2 instances of male-to-male transmission. The appearance as pictured from both the Venezuelan and the Turkish family was striking. The syndrome is easily distinguished from frontonasal dysplasia (136760) and from craniofrontonasal dysplasia (304110), which it only superficially resembles.
Bock-Kunz et al. (2000) described the ophthalmic manifestations and clinical course of a newborn with nasopalpebral lipoma-coloboma syndrome. In addition to the ocular and maxillofacial findings described in the existing literature, the patient had small amplitude jerk nystagmus with a latent component, high hyperopic astigmatism, and variable, intermittent exotropia which resolved with part-time occlusion of the preferred eye. Surgery was performed to repair the bilateral upper eyelid coloboma and remove the bilateral nasopalpebral lipomata. Cytogenetic studies revealed no evidence of chromosomal abnormality, and the authors concluded that the patient's craniofacial dysmorphism had resulted from a spontaneous mutation.
Suresh et al. (2011) described a sporadic case of nasopalpebral lipoma-coloboma syndrome in a 16-year-old Indian girl, born of nonconsanguineous parents. In addition to the typical features of the disorder, she had a limbal dermoid.
Chacon-Camacho et al. (2013) reported a 7-month-old Mexican girl with NPLCS, who was born with bilateral symmetric accumulation of subcutaneous tissue in the nasopalpebral region, extending to the forehead and upper lip. Examination at 2 months of age showed a round soft tumor displacing the inner canthi laterally, causing marked telecanthus. There were symmetric colobomata of upper and lower lids at the junction of the inner and middle thirds of lids, as well as absence or displacement of upper and lower lacrimal punctae with bilateral epiphora, and medial eyelashes were absent. In addition, she had dolichocephaly, broad forehead, widow's peak, sparse and maldirected eyebrows, broad and depressed nasal bridge, and low-set, cupped, and dysplastic ears. At age 7 months the forehead and nasopalpebral tumors were more prominent and covered the medial segment of the irides. Physical examination revealed bilateral fifth finger clinodactyly, but no other systemic anomalies. Eye ultrasound was consistent with bilateral nanophthalmos, and CT scan of the head showed maxillary hypoplasia, normal interorbital distance, and lipomatous tissue covering the nasopalpebral regions, but no brain malformation. Biopsy of forehead skin and subcutaneous tissue was compatible with smooth muscle hamartoma mixed with lipomatous tissue. Chacon-Camacho et al. (2013) stated that this was the sixth reported patient with NPLCS.
InheritanceThe transmission pattern of NPLCS in the families reported by Penchaszadeh et al. (1982) and Akarsu and Sayli (1991) was consistent with autosomal dominant inheritance with complete penetrance.
Molecular GeneticsFor discussion of a possible association between variation in the ZDBF2 gene and nasopalpebral lipoma-coloboma syndrome, see 617059.0001.