Which are the causes of SHORT syndrome?

SHORT syndrome is a rare genetic disorder characterized by a variety of physical and developmental abnormalities. The acronym SHORT stands for Short stature, Hyperextensibility of joints, Ocular depression, Rieger anomaly, and Teething delay. This condition affects multiple systems in the body, leading to a range of symptoms and complications.

Genetic mutations are the primary cause of SHORT syndrome. Most cases are sporadic, meaning they occur randomly and are not inherited from parents. However, in some instances, the condition can be inherited in an autosomal dominant manner, where a mutation in a single copy of a specific gene is sufficient to cause the disorder.

Researchers have identified that mutations in the PIK3R1 gene are responsible for the majority of SHORT syndrome cases. The PIK3R1 gene provides instructions for producing a protein that is involved in cell signaling pathways. Mutations in this gene disrupt the normal functioning of these pathways, leading to the characteristic features of SHORT syndrome.

The exact mechanisms by which PIK3R1 mutations cause the specific symptoms of SHORT syndrome are not fully understood. However, it is believed that the mutations affect the growth and development of various tissues and organs, resulting in short stature, joint hyperextensibility, and ocular and dental abnormalities.

Short stature is a prominent feature of SHORT syndrome, with affected individuals typically being significantly shorter than their peers. The underlying cause of this growth impairment is thought to be related to skeletal abnormalities and delayed bone maturation.

Joint hyperextensibility refers to the ability of joints to move beyond their normal range of motion. In SHORT syndrome, this hypermobility is often present in multiple joints, making them more flexible and prone to injury.

Ocular depression is characterized by downward slanting of the outer corners of the eyes. This feature can give the eyes a "sad" or "droopy" appearance.

Rieger anomaly is a condition affecting the eyes, specifically the iris and other structures in the front part of the eye. It can cause abnormalities in the shape, size, and color of the iris, as well as glaucoma and other vision problems.

Teething delay is another common manifestation of SHORT syndrome. Children with this condition often experience delayed eruption of primary and permanent teeth, which can lead to dental complications and require specialized dental care.

It is important to note that the severity and specific combination of symptoms can vary among individuals with SHORT syndrome. Some affected individuals may have additional features or health issues not mentioned above.

Diagnosis of SHORT syndrome is typically based on clinical evaluation, identification of characteristic features, and genetic testing to confirm the presence of PIK3R1 gene mutations. Management of the condition involves addressing the specific symptoms and providing appropriate medical care and support.