ICD-10 Q87.0 OMIM 101600 MeSH D000168 | ICD-9-CM 755.55 DiseasesDB 32145 Orphanet 710 | |
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Pfeiffer syndrome is a very rare genetic disorder characterized by the premature fusion of certain bones of the skull 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 affects about 1 in 100,000 births.
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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). About 50 percent of children with Pfeiffer syndrome have hearing loss, and dental problems are also common.
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).
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:
Genetics
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. 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.
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 problems 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 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.