SNP Shot: Genomic Insights

Stickler syndrome encompasses a group of inherited disorders characterized by distinctive facial features, eye problems, hearing loss, and joint issues. The specific symptoms and their severity can vary considerably among affected individuals.

A common characteristic of Stickler syndrome is a somewhat flattened facial appearance, resulting from underdeveloped bones in the mid-face, specifically the cheekbones and nasal bridge. Many individuals also exhibit Pierre Robin sequence, a cluster of features that includes a cleft palate (an opening in the roof of the mouth), glossoptosis (a tongue positioned further back than usual), and micrognathia (a small lower jaw). This combination can lead to difficulties with feeding and breathing.

Nearsightedness (high myopia) is prevalent in those with Stickler syndrome, causing difficulty seeing distant objects. Abnormalities in the vitreous, the gel-like substance filling the eyeball, are often observed during eye exams. Other eye problems, such as glaucoma (increased eye pressure), cataracts (clouding of the lens), and retinal detachment (tearing of the eye's lining), are also common and can lead to impaired vision or blindness.

Hearing loss in Stickler syndrome varies in severity and may worsen over time. It can be sensorineural, stemming from inner ear changes, or conductive, resulting from middle ear abnormalities.

Skeletal abnormalities affecting the joints are common in Stickler syndrome. Children and young adults may have unusually flexible (hypermobile) joints, but this flexibility tends to decrease with age. Early-onset arthritis, causing joint pain and stiffness, is frequent. Spinal problems, such as scoliosis or kyphosis (abnormal spinal curvature) and platyspondyly (flattened vertebrae), can also occur, potentially leading to back pain.

Researchers have identified several types of Stickler syndrome, distinguished by their genetic causes and symptom patterns. Eye abnormalities and the severity of hearing loss vary between types. Type I carries the highest risk of retinal detachment. Type II also includes eye abnormalities, whereas type III does not (often referred to as non-ocular Stickler syndrome). Types II and III are more likely to involve significant hearing loss than Type I. Types IV, V, and VI are very rare, each diagnosed in only a handful of individuals.

Marshall syndrome, a condition similar to Stickler syndrome, also features distinctive facial features, eye abnormalities, hearing loss, and early arthritis. Short stature can also be a feature of Marshall syndrome. While some researchers consider Marshall syndrome a variant of Stickler syndrome, others classify it as a distinct disorder.

Inheritance:

Stickler syndrome types I, II, and III follow an autosomal dominant inheritance pattern. This means only one copy of the mutated gene in each cell is needed to cause the disorder. In some cases, an affected person inherits the mutated gene from a parent who also has the condition. Other cases result from new mutations, occurring in individuals with no family history of Stickler syndrome. Marshall syndrome also typically exhibits autosomal dominant inheritance. Stickler syndrome types IV, V, and VI follow an autosomal recessive inheritance pattern. This requires two copies of the mutated gene in each cell for the condition to develop. The parents of someone with an autosomal recessive condition each carry one copy of the mutated gene but usually don't show any symptoms of the condition themselves.