Pfeiffer syndrome is a rare autosomal dominant disorder, characterized by malformations of the skull, face, hands and feet. Crouzon, Apert and Pfeiffer syndromes are the most recognizable of the syndromic craniosynostosis. Diagnoses can be established from the typical phenotype accompanied by molecular genetic testing.
Most cases can be attributed to mutations in the fibroblast growth factor receptor genes FGFR-1 or FGFR-2. However there are phenotypes that cannot be related to FGFR abnormalities. Based on the severity of malformations it is divided into three clinical subtypes. Type 1 “classic” Pfeiffer syndrome is by far the most common subtype and presents with mild manifestations of brachycephaly, midface hypoplasia and broad fingers and toes; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, airway malformations, developmental delay, neurological complications and decreased life span. Type 3 is similar to type 2 but without a cloverleaf skull. Clinical overlap between the three types may occur.
Craniosynostosis (premature fusion of one or more of the cranial sutures) most often involves coronal and lambdoid sutures. This prevents further growth of the skull, affects the shape of the head and face and may lead to increased intracranial pressures. Possible atresia of the external auditory canal will lead to conductive hearing loss. Fused vertebrae, Arnold-Chiari malformation and seizures may be present. The underdeveloped maxillary results in very shallow orbitae and proptosis, which may lead to corneal damage from xerophtalmia.
Maxillary hypoplasia also results in a small nasopharynx and hypopharynx, which may restrict air passage, cause obstructive sleep apnoea, restrict the passage of food into the œsophagus, and lead to gastric reflux and possibly recurring aspirations. Cleft palate and choanal atresia are common. In the rare cases of ACS5 Type 2 and 3, extensive airway affections, such as tracheal stenosis, tracheo-cartilagenous sleeve, and tracheobronchial malacia have been reported.
Hand and feet involvement may range from broad and radially deviated thumbs and big toes to syn- and brachydactyly.
Even though rare, the spectrum of internal organ anomalies is broad and may comprise congenital cardiac malformations.
The prognosis depends mainly on the severity of the associated anomalies of central nervous and respiratory systems. Patients with type 1 PS generally have good prognosis whereas type 2 and 3 PS is usually associated with early demise in infancy or childhood. An early and coordinated multidisciplinary medical and surgical approach is indicated.