ZDBF2 – Nasopalpebral Lipoma-coloboma Syndrome

This report details the association between ZDBF2 and nasopalpebral lipoma-coloboma syndrome. ZDBF2 (HGNC:29313) has recently been implicated in this rare disorder (MONDO_0008182), which is characterized by a distinctive combination of facial features including lipomas, eyelid colobomas, telecanthus, and maxillary hypoplasia (PMID:27139419).

In a sporadic patient presenting with these phenotypic traits, exome sequencing identified a de novo heterozygous frameshift mutation in ZDBF2, marking the first instance of a genetic defect associated with nasopalpebral lipoma-coloboma syndrome. This single proband (PMID:27139419) provided the initial evidence linking ZDBF2 to the disease.

The genetic evidence is centered on a de novo frameshift mutation, specifically the variant c.6245_6246 insTT (p.His2082fsTer67). This variant, detected in the affected individual and absent from parental DNA and control populations, provides preliminary support for a pathogenic role of ZDBF2 disruptions in this syndrome (PMID:27139419).

Nasopalpebral lipoma-coloboma syndrome is reported to follow an autosomal dominant mode of inheritance, consistent with the de novo nature of the observed mutation. No additional affected relatives showing segregating variants have been reported, which is typical in a sporadic case scenario (PMID:27139419).

Although detailed functional studies are not yet available, preliminary experimental assessments suggest that the frameshift mutation in ZDBF2 likely results in a loss-of-function, paving the way for haploinsufficiency. Such a mechanism is consistent with the clinical features observed in affected individuals (PMID:27139419).

The phenotype observed in the proband, which includes maxillary hypoplasia (HP:0000327) and telecanthus (HP:0000506), aligns well with the clinical description of nasopalpebral lipoma-coloboma syndrome, providing further clinical context to support the genetic finding.

In summary, despite the association being derived from a single de novo mutation event and preliminary functional insights, the observed genetic and phenotypic concordance supports its relevance in diagnostic decision‑making. Key take‑home: This association, while currently limited, offers a promising molecular marker for nasopalpebral lipoma‑coloboma syndrome and underscores the need for further studies to consolidate the pathogenic framework.

References

• American journal of medical genetics. Part A • 2016 • Exome sequencing identifies a de novo frameshift mutation in the imprinted gene ZDBF2 in a sporadic patient with Nasopalpebral Lipoma-coloboma syndrome PMID:27139419

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