ROTH SPOTS IN A RENDU-OSLER-WEBER SYNDROME

Area of Science:

• Genetics
• Ophthalmology
• Neurology

Background:

• Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is an autosomal dominant disorder.
• Juvenile polyposis syndrome (JPS) is a gastrointestinal disorder characterized by multiple polyps.
• The co-occurrence of HHT and JPS is rare and suggests a potential shared genetic pathway.

Purpose of the Study:

• To describe the molecular diagnosis of a patient with coexisting Rendu-Osler-Weber syndrome and juvenile polyposis syndrome.
• To document the atypical ocular presentation in this patient.
• To investigate the genetic basis for the combined syndromes.

Main Methods:

• Case report of a 35-year-old female patient.
• Ocular examination including funduscopy.
• Neurological imaging: brain MRI and arteriography.
• Next-generation sequencing for genetic testing.

Main Results:

• The patient presented with right hemiplegia, homonymous hemianopia, and sensory deficit.
• Ocular findings included Roth spots in the left fundus.
• Genetic testing identified a pathogenic SMAD-4 gene variation (c.1245_1248del) in heterozygous state.
• A carotid-ophthalmic aneurysm was noted, an unusual finding in HHT.

Conclusions:

• The study highlights an unusual presentation of HHT associated with JPS.
• The identified SMAD-4 mutation may be linked to the observed atypical features, including the carotid-ophthalmic aneurysm.
• This case underscores the importance of molecular diagnosis in understanding complex genetic syndromes and their varied manifestations.