[Familial Wolfram syndrome].

Area of Science:

• Genetics
• Neuroscience
• Pediatrics

Background:

• Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder.
• Key features include diabetes mellitus and optic atrophy, with other symptoms like diabetes insipidus and deafness being less common.
• The WFS1 gene on chromosome 4p16 encodes wolframin and is linked to WS.

Purpose of the Study:

• To report a familial case of Wolfram syndrome.
• To highlight the importance of recognizing WS in pediatric patients presenting with specific symptoms.
• To confirm the diagnosis through molecular analysis.

Main Methods:

• Clinical observation of a family with suspected Wolfram syndrome (parents and three children).
• Detailed family history collection, noting symptoms such as diabetes mellitus, optic atrophy, deafness, and hydronephrosis.
• Molecular genetic analysis to identify WFS1 gene mutations.

Main Results:

• The propositus, a 6-year-old girl, presented with diabetes mellitus and progressive vision loss.
• Family history revealed affected siblings with diabetes mellitus, optic atrophy, deafness, and bilateral hydronephrosis.
• Molecular analysis confirmed homozygous WFS1 mutations (c.1113G>A) in the three siblings and heterozygous mutations in the parents.

Conclusions:

• The presented familial case strongly suggests Wolfram syndrome based on clinical and genetic findings.
• Early recognition of Wolfram syndrome is crucial for pediatricians, especially in diabetic children with optic atrophy.
• Molecular confirmation of WFS1 mutations solidifies the diagnosis and aids in understanding familial inheritance patterns.