Pfeiffer syndrome is a rare genetic disorder characterized by the premature fusion of certain bones of the skull (craniosynostosis) which affects the shape of the head and face. In addition, the syndrome includes abnormalities of the hands (such as wide and deviated thumbs) and feet (such as wide and deviated big toes). Pfeiffer syndrome is caused by mutations in the fibroblast growth factor receptors FGFR1 and FGFR2. The syndrome is grouped into three types, type 1 (classic Pfeiffer syndrome) being milder and caused by mutations in either gene and types 2 and 3 being more severe, often leading to death in infancy, caused by mutations in FGFR2. There is no cure for the syndrome. Treatment is supportive and often involves surgery in the earliest years of life to correct skull deformities and respiratory function. Most individuals with Pfeiffer syndrome type 1 have a normal intelligence and life span, while types 2 and 3 typically result in neurodevelopmental disorders and early death. Pfeiffer syndrome affects about 1 in 100,000 births. The syndrome is named after German geneticist Rudolf Arthur Pfeiffer (1931–2012), who described it in 1964. Signs and symptoms Many of the characteristic facial features result from the premature fusion of the skull bones (craniosynostosis). The head is unable to grow normally, which leads to a high prominent forehead (turribrachycephaly), and eyes that appear to bulge (proptosis) and are wide-set (hypertelorism). In addition, there is an underdeveloped upper jaw (maxillary hypoplasia). More than 50 percent of children with Pfeiffer syndrome have hearing loss; dental problems are also common. Babies with Pfeiffer syndrome may also exhibit a small, beak-shaped nose; crowded, crooked teeth; and sleep apnea due to nasal airway blockage. There are three main types of Pfeiffer syndrome, with type I being the mildest and most common, type II being the most severe with added neurological problems and a cloverleaf deformity, and type III being similar to type II but without the cloverleaf deformity. In people with Pfeiffer syndrome, the thumbs and first (big) toes are wide and bend away from the other digits (pollex varus and hallux varus). Unusually short fingers and toes (brachydactyly) are also common, and there may be some webbing or fusion between the digits (syndactyly). Cause Pfeiffer syndrome is strongly associated with mutations of the fibroblast growth factor receptor 1 (FGFR1) on chromosome 8 or the fibroblast growth factor receptor 2 (FGFR2) gene on chromosome 10.