Clinical features of syndromic microphthalmia in two novel RARB variants

Area of Science:

• Genetics
• Ophthalmology
• Developmental Biology

Background:

• Syndromic microphthalmia-12 is a rare congenital eye disorder.
• The genetic basis for many forms of syndromic microphthalmia remains poorly understood.

Purpose of the Study:

• To identify the genetic cause of syndromic microphthalmia-12 in two unrelated Japanese patients.
• To characterize the clinical phenotypes associated with novel RARB variants.

Main Methods:

• Whole exome sequencing was performed on affected individuals.
• Segregation analysis and in silico predictions were used to assess variant pathogenicity.

Main Results:

• Two distinct heterozygous RARB gene variants were identified: a frameshift variant (c.1205_1206del) in Case 1 and a missense variant (c.844G>T) in Case 2.
• Case 1 presented with bilateral microphthalmia, corneal opacity, anterior segment dysgenesis, multiorgan anomalies, hypotonia, and cognitive impairment.
• Case 2 exhibited Peters anomaly, extreme microphthalmia, spasticity, profound psychomotor delay, and refractory epilepsy.

Conclusions:

• Heterozygous RARB variants are a cause of syndromic microphthalmia-12.
• Clinical manifestations associated with RARB variants are diverse, ranging from ocular anomalies to severe systemic and neurological deficits.
• RARB gene testing should be considered in the diagnostic workup of patients with syndromic microphthalmia.