Case report of a PRDM5 linked brittle cornea syndrome type 2 in association with a novel SLC6A5 mutation

Area of Science:

• Genetics
• Ophthalmology
• Neurology

Background:

• Brittle cornea syndrome 2 (BCS2) is a rare genetic disorder affecting connective tissues, often involving ocular abnormalities.
• Hyperekplexia is a neurological disorder characterized by exaggerated startle responses.

Observation:

• A 3-year-old girl presented with blue sclera, joint hyperlaxity, hip dysplasia, bilateral corneal thinning, astigmatism, and keratoconus.
• Clinical exome sequencing was performed to investigate the underlying genetic cause.

Findings:

• A frameshift mutation (c.713_716 del TTTG p.(Val238Alafs*35)) in the PRDM5 gene was identified, confirming a diagnosis of brittle cornea syndrome 2.
• A novel homozygous frameshift mutation (c.401dup p.(Ser135Glufs*53)) in the SLC6A5 gene was discovered, associated with Hyperekplexia 3.
• The proband exhibited no clinical features of hyperekplexia at the time of examination.

Implications:

• This case highlights the genetic overlap and phenotypic variability in rare connective tissue and neurological disorders.
• The identification of a novel SLC6A5 mutation provides insight into the genetic basis of hyperekplexia.
• Genetic counseling is important to inform the family about the potential for future neurological symptoms related to the SLC6A5 mutation.