Foveal hypoplasia in Myhre syndrome: a novel association

Myhre syndrome is an autosomal dominant condition caused by pathogenic variants in the transcriptional co-regulator SMAD4. Myhre syndrome is characterized by distinctive facial features, short stature, musculoskeletal abnormalities, and intellectual disability. Reported ocular abnormalities include refractive errors, corectopia, cataract, strabismus, and pseudo) papilledema.

We describe an 8-year-old boy with Myhre syndrome due to a c.1498A > G; p.I500V pathogenic variant in SMAD4. Ocular examination revealed bilateral emmetropia, mild visual acuity reduction in the right eye (20/25), grade 1b foveal hypoplasia in both eyes and small optic discs with pseudopapilledema.

This report marks the first reported case of foveal hypoplasia in Myhre syndrome, a potentially underreported finding, given the relative lack of OCT assessment in patients with Myhre syndrome. We discuss pathophysiological link between foveal hypoplasia and gain-of-function variants in SMAD4.