Frank-Ter Haar syndrome

Frank-Ter Haar syndrome (FTHS), also known as Ter Haar syndrome or megalocornea-skeletal anomalies-facial dysmorphism syndrome, is a rare autosomal recessive disorder characterized by a distinctive combination of skeletal, craniofacial, cardiac, and ocular abnormalities. It is caused by mutations in the SH3PXD2B gene (also known as TKS4), which encodes a protein involved in extracellular matrix remodeling through its role in podosome and invadopodia formation. The condition is typically apparent at birth or in early infancy. Key clinical features include a characteristic facial appearance with prominent eyes, hypertelorism (widely spaced eyes), a broad mouth, full cheeks, and micrognathia (small jaw). Skeletal abnormalities are prominent and include bowing of the long bones, kyphoscoliosis, joint contractures, brachydactyly (short fingers), and delayed closure of the anterior fontanelle with wide cranial sutures. Ocular findings frequently include megalocornea (abnormally large corneas) and glaucoma, which can be severe and progressive. Congenital heart defects, particularly mitral valve prolapse and other valve abnormalities, are commonly observed. Some patients may also develop cardiac hypertrophy. The prognosis of Frank-Ter Haar syndrome is variable, but the condition can be severe, with some affected individuals dying in infancy or early childhood due to cardiac complications or recurrent infections. There is currently no specific or curative treatment for FTHS. Management is supportive and multidisciplinary, involving orthopedic care for skeletal abnormalities, ophthalmologic monitoring and treatment for glaucoma, cardiac surveillance, and developmental support. Surgical interventions may be necessary for cardiac defects or to manage increased intraocular pressure. Early diagnosis and coordinated care are essential to optimize outcomes.

Common questions about Frank-Ter Haar syndrome