IllnessStickler syndrome, differential diagnosis II; enlargement panel

NGS +

Stickler syndrome is a hereditary vitreoretinopathy in which the ocular symptomatology is associated with a more or less severe Pierre-Robin sequence, bone abnormalities, and (in 10% of cases) sensorineural hearing loss. Ocular symptoms include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment and chronic uveitis. Hyperextensibility of the joints in youth is followed early by arthritic changes. Mild platyspondyly, scoliosis and enlarged, often abnormal epiphyses are observed. Stickler syndrome is inherited in an autosomal dominant or rarely autosomal recessive manner and is genetically heterogeneous. Mutations are identified in the COL2A1, COL11A1, COL11A2, COL9A1, COL9A2 and COL9A3 genes - the panel includes all of these genes. DNA tests are used for differential diagnosis and thus for genetic counseling of the index person and relatives. The diagnostic yield of the panel amounts to 90% (80-90% of the cases harbor COL2A1 mutations, 10-20% COL11A1 mutations). Additional genes are rarely associated with the disease. A negative molecular genetic finding does not definitely exclude the clinical diagnosis.

This additional panel includes other genes that are particularly relevant for differential diagnosis of aspects of Stickler syndrome, such as myopia and vitreoretinopathy. Approximately half of all individuals with Pierre-Robin sequence have an underlying syndrome, Stickler syndrome being the most common. 20-30% of patients with Pierre-Robin sequence have Stickler syndrome.

References: https://www.ncbi.nlm.nih.gov/books/NBK1302/

https://doi.org/10.3390/jpm10030105

• Alias: Arthroophthalmopathy
• Alias: Hereditary progressive arthroophthalmopathy
• Allelic: Leber congenital amaurosis 16 (KCNJ13)
• Allelic: Mitochondrial complex IV deficiency, nuclear type 2 (SCO2)
• Myopia 21, AD (ZNF644)
• Myopia 22, AD (PRIMPOL syn. CCDC111)
• Myopia 23, AR (LRPAP1)
• Myopia 24, AD (SLC39A5)
• Myopia 25, AD (P4HA2)
• Myopia 26, XL, female-limited (ARR3)
• Myopia 27 (CPSF1)
• Myopia 6 (SCO2)
• Persistent hyperplastic primary vitreous, AR (ATOH7)
• Snowflake vitreoretinal degeneration (KCNJ13)
• Wagner syndrome 1 [erosive vitreoretinopathy] (VCAN)