Ardalan–Shoja–Kiuru syndrome

Overview

Ardalan–Shoja–Kiuru Syndrome is an extremely rare, recently described genetic condition characterized by a combination of hereditary gelsolin amyloidosis and retinitis pigmentosa. This syndrome represents a unique clinical overlap between a systemic amyloidosis disorder and a degenerative retinal disease, distinguishing it from classical familial amyloidosis types.

It was first identified in an Iranian family and named after the researchers who described it. The combination of ocular and systemic features suggests a novel genetic or molecular mechanism that affects both connective tissue stability and retinal integrity.

Causes

The exact genetic mutation responsible for Ardalan–Shoja–Kiuru Syndrome has not been fully characterized. However, it is thought to be related to a variant of the GSN gene, which encodes the protein gelsolin. Mutations in GSN are known to cause familial amyloidosis of the Finnish type (FAF), typically leading to amyloid deposition in various tissues.

This syndrome appears to follow an autosomal dominant inheritance pattern, although only a few cases have been reported to date.

Symptoms

The syndrome presents a unique combination of systemic and ocular features. Key symptoms include:

Systemic Features (amyloidosis-related):

• Cranial and peripheral neuropathy

• Cutis laxa (loose skin)

• Lattice corneal dystrophy

• Progressive facial muscle weakness

• Speech difficulties due to oropharyngeal involvement

Ocular Features (retinal involvement):

• Night blindness (nyctalopia)

• Progressive visual field loss

• Retinal pigment changes consistent with retinitis pigmentosa

• Eventual loss of central vision

The combination of gelsolin amyloidosis and retinal degeneration is unique to this syndrome and helps distinguish it from other hereditary amyloidoses.

Diagnosis

Diagnosis of Ardalan–Shoja–Kiuru Syndrome involves a combination of clinical evaluation, genetic testing, and ophthalmologic examination:

• Ophthalmic evaluation: Fundus photography, visual field testing, and electroretinography (ERG) consistent with retinitis pigmentosa

• Neurological assessment: Detection of peripheral neuropathy and facial weakness

• Skin and corneal biopsy: May reveal amyloid deposits

• Genetic testing: Investigation of the GSN gene or whole-exome sequencing may reveal the mutation

Treatment

There is currently no cure for Ardalan–Shoja–Kiuru Syndrome, and treatment is focused on supportive care and symptom management:

Systemic Management:

• Physical therapy for neuropathy

• Speech therapy and swallowing support if facial muscles are affected

• Regular monitoring for cardiac or renal involvement if systemic amyloidosis progresses

Ocular Management:

• Low vision aids

• Vitamin A supplementation (under medical supervision) in select retinitis pigmentosa cases

• Ongoing ophthalmologic care for retinal monitoring

Genetic Counseling:

• Recommended for affected families due to the autosomal dominant inheritance pattern

Prognosis

Ardalan–Shoja–Kiuru Syndrome is progressive. The severity and rate of deterioration vary among individuals, but common concerns include:

• Gradual visual impairment leading to blindness

• Progressive neuromuscular symptoms and possible facial disfigurement

• Quality of life impacted by both sensory and motor decline

Early detection and multidisciplinary care can help manage complications and maintain patient independence as long as possible. Research into targeted therapies or gene-based interventions may offer hope in the future.