Case report: ocular manifestations of NFIX-associated Malan syndrome

Ophthalmic Genet. 2025 Aug;46(4):394-396. doi: 10.1080/13816810.2025.2482609. Epub 2025 Mar 24.

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Malan syndrome; Marshall-Smith syndrome; NFIX; Sotos syndrome; ocular manifestations.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple* / genetics
  • Humans
  • Intellectual Disability* / diagnosis
  • Intellectual Disability* / genetics
  • Male
  • Megalencephaly* / diagnosis
  • Megalencephaly* / genetics
  • NFI Transcription Factors* / genetics
  • Optic Atrophy* / diagnosis
  • Optic Atrophy* / genetics
  • Sotos Syndrome / diagnosis
  • Sotos Syndrome / genetics
  • Visual Acuity

Substances

  • NFI Transcription Factors