These genes code for fibroblast growth factor receptors, which are important for normal bone development. Advanced paternal age is thought to be a risk factor for sporadic cases of Pfeiffer syndrome due to an increase in mutations in sperm as men become older. Diagnosis Classification The most widely accepted clinical classification of Pfeiffer syndrome was published by M. Michael Cohen in 1993. Cohen divided the syndrome into three possibly overlapping types, all of which are characterized by broad thumbs, broad great toes, brachydactyly and possibly syndactyly: Type 1, also known as classic Pfeiffer syndrome, includes craniosynostosis and "midface deficiency". This type is inherited in an autosomal dominant pattern. Most individuals with type 1 Pfeiffer syndrome have normal intelligence and a normal life span. Type 2 includes a cloverleaf-shaped skull, due to extensive fusion of bones, as well as severe proptosis. This type occurs sporadically (i.e., does not appear to be inherited) and has "a poor prognosis and severe neurological compromise, generally with early death". Type 3 includes craniosynostosis and severe proptosis. This type occurs sporadically (i.e., does not appear to be inherited) and has "a poor prognosis and severe neurological compromise, generally with early death." Management The key problem is the early fusion of the skull, which can be corrected by a series of surgical procedures, often within the first three months after birth. Later surgeries are necessary to correct respiratory and facial deformities. Outcomes Children with Pfeiffer syndrome types 2 and 3 "have a higher risk for neurodevelopmental disorders and a reduced life expectancy" than children with Pfeiffer syndrome type 1, but if treated, favorable outcomes are possible. In severe cases, respiratory and neurological complications often lead to early death. History The syndrome is named after German geneticist Rudolf Arthur Pfeiffer (1931–2012). In 1964, Pfeiffer described eight individuals in three generations of a family who had abnormalities of the head, hands and feet (acrocephalosyndactylia) that were inherited in an autosomal dominant pattern. Notable cases In 1996, a son was born to American musician Prince and his wife Mayte Garcia. The highly anticipated child, Amiir ("prince" in Arabic), was diagnosed at birth with Pfeiffer syndrome type 2 and died several days later. In 1997, after Garcia's former personal assistants raised concerns about the manner of death, the medical examiner performed an investigation and declared that the death was due to natural causes (meaning it was not a homicide). In 2014,