SHORT syndrome

SHORT syndrome is an extremely rare multisystem disorder whose name is an acronym describing its cardinal features: Short stature, Hyperextensibility of joints and/or inguinal hernia, Ocular depression (deeply set eyes), Rieger anomaly (a developmental defect of the anterior chamber of the eye), and Teething delay. The condition is caused by heterozygous mutations in the PIK3R1 gene, which encodes a regulatory subunit of phosphatidylinositol 3-kinase (PI3K), a key enzyme involved in insulin signaling and cell growth. Patients with SHORT syndrome typically present with intrauterine growth restriction and postnatal short stature. Facial features are characteristic and include a triangular face, deeply set eyes, thin and wrinkled skin (particularly noticeable in the hands), underdeveloped subcutaneous fat (partial lipodystrophy), and a small chin. Rieger anomaly of the eye can lead to glaucoma, which requires careful ophthalmologic monitoring. Insulin resistance and, in some cases, overt diabetes mellitus are significant metabolic complications that may develop during childhood or adolescence. Other features can include delayed speech development, mild cognitive differences (though intelligence is often normal), delayed dental eruption, and nephrocalcinosis. There is currently no cure for SHORT syndrome, and management is supportive and symptom-directed. Treatment may include monitoring and management of insulin resistance or diabetes, ophthalmologic surveillance and treatment for glaucoma, dental care for delayed eruption, and growth monitoring. A multidisciplinary approach involving endocrinology, ophthalmology, genetics, and other specialties is recommended. Early recognition of the condition allows for proactive screening of known complications, particularly glaucoma and metabolic disturbances.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about SHORT syndrome