PLXND1 – Moebius syndrome

Moebius syndrome (MBS) is characterized by congenital facial and abducens nerve palsies. In a single MBS patient, fine mapping of a complex germline chromothriptic rearrangement revealed truncation of one allele of PLXND1, encoding the plexin-D1 receptor essential for semaphorin signaling, suggesting a role in cranial nerve development (PMID:31033088).

No additional pathogenic PLXND1 variants or familial segregations have been described in larger MBS cohorts, and no functional assays specifically assessing PLXND1 variants in MBS models have been performed. The limited genetic and experimental data thus restrict the clinical validity of PLXND1 in MBS to a “Limited” level.

Key take-home: While a single truncating PLXND1 lesion implicates plexin-D1 in MBS, further replication and functional studies are required before clinical implementation.

References

• Human Mutation • 2019 • Multigenic truncation of the semaphorin-plexin pathway by a germline chromothriptic rearrangement associated with Moebius syndrome. PMID:31033088

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