Multiple synostoses syndrome: Clinical report and retrospective analysis

Area of Science:

• Genetics
• Medical Genetics
• Rare Diseases

Background:

• Multiple synostoses syndrome (SYNS1) is a rare autosomal dominant disorder.
• It is characterized by joint fusions, conductive hearing loss, and distinctive facial features.
• Few cases have been reported globally.

Purpose of the Study:

• To investigate the genetic cause of SYNS1 in a Chinese family.
• To review the pathogeny, treatment, and prevention of SYNS1.
• To expand the mutation spectrum of the NOG gene.

Main Methods:

• Clinical examinations (audiological, ophthalmological, radiological).
• Whole-exome sequencing (WES) and Sanger sequencing.
• Bioinformatic analysis and literature review.

Main Results:

• A novel missense mutation (c.554C>G, p.Ser185Cys) in the NOG gene was identified and segregated in the family.
• This is the first report of SYNS1 in a Chinese family.
• Phenotypic variability exists, but conductive hearing loss and proximal symphalangism are common.

Conclusions:

• Genetic testing, including WES, is crucial for diagnosing syndromic deafness.
• Clinical genetic evaluation aids in prevention strategies like preimplantation genetic diagnosis.
• While hearing aids are beneficial, surgical outcomes for hearing loss in SYNS1 are often limited.