Case report: ocular manifestations of NFIX-associated Malan syndrome

Malan syndrome, an overgrowth disorder caused by pathogenic NFIX gene variants, is characterized by macrocephaly, distinct facial features, and intellectual disability. This case highlights the associated ophthalmologic features of this rare condition.

We describe a young Spanish white man with progressive vision loss in the setting of a prior clinical diagnosis of Sotos syndrome, accompanied by developmental delay and epilepsy.

Ophthalmic examination and imaging studies revealed visual acuity of 20/50 in each eye and bilateral optic atrophy. Genetic testing identified a heterozygous pathogenic NFIX variant, confirming Malan syndrome rather than NSD1-related Sotos syndrome.

This case underscores the importance of genetic testing in patients with syndromic features, highlighting Malan syndrome as a differential diagnosis in cases of optic atrophy with overgrowth phenotypes.