|Infant with Pfeiffer syndrome type 1, showing brachycephaly, coronal synostosis, broad and deviated thumbs and big toes, and finger and toe syndactyly|
|Frequency||1 per 100,000 births|
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.
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).
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.
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 (Kleeblattschädel) 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."
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.
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.
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.
Society and culture
- In 1996, a baby boy was born to the artist formerly known as Prince and wife Mayte Garcia. The highly anticipated child named Amiir (which means "prince" in Arabic), was diagnosed at birth with Pfeiffer syndrome type 2, which is incompatible with life. The infant survived several days until the parents agreed that heroic measures be discontinued. In 1997, after Garcia's former personal assistants raised concerns about the manner of death, the Hennepin County, Minnesota medical examiner performed an investigation and declared that the death was due to natural causes (i.e., was not a homicide).
- In 2014, a mother of a boy in Texas with Pfeiffer syndrome type 1 posted a photograph of the child to her blog. In 2016, she discovered that the photograph had been used in a meme comparing her son to a pug. Her efforts to remove the meme from the Internet, especially social media such as Instagram, Twitter, and Facebook, attracted international attention.
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- Muenke M; Schell U; Hehr A; Robin NH; Losken HW; Schinzel A; et al. (1994). "A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome". Nat Genet. 8 (3): 269–74. PMID 7874169. doi:10.1038/ng1194-269.
- Rutland P; Pulleyn LJ; Reardon W; Baraitser M; Hayward R; Jones B; et al. (1995). "Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes". Nat Genet. 9 (2): 173–6. PMID 7719345. doi:10.1038/ng0295-173.
- Schell U, Hehr A, Feldman GJ, Robin NH, Zackai EH, de Die-Smulders C, et al. (1995). "Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome". Hum Mol Genet. 4 (3): 323–8. PMID 7795583. doi:10.1093/hmg/4.3.323.
- Chan CT, Thorogood P (1999). "Pleiotropic features of syndromic craniosynostoses correlate with differential expression of fibroblast growth factor receptors 1 and 2 during human craniofacial development". Pediatr Res. 45 (1): 46–53. PMID 9890607. doi:10.1203/00006450-199901000-00008.
- Glaser RL, Jiang W, Boyadjiev SA, Tran AK, Zachary AA, Van Maldergem L, et al. (2000). "Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome". Am J Hum Genet. 66 (3): 768–77. PMC . PMID 10712195. doi:10.1086/302831.
- National Institutes of Health, Genetic and Rare Diseases (GARD) Information Center (2016-04-01). "Pfeiffer syndrome: Symptoms". Retrieved 2016-05-08.
- Cohen MM (1993). "Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis". Am J Med Genet. 45 (3): 300–7. PMID 8434615. doi:10.1002/ajmg.1320450305.
- Robin NH; Scott JA; Arnold JE; Goldstein JA; Shilling BB; Marion RW; et al. (1998). "Favorable prognosis for children with Pfeiffer syndrome types 2 and 3: implications for classification". Am J Med Genet. 75 (3): 240–4. PMID 9475589. doi:10.1002/(sici)1096-8628(19980123)75:3<240::aid-ajmg2>3.3.co;2-c.
- synd/3477 at Who Named It?
- Pfeiffer RA (1964). "Dominant erbliche Akrocephalosyndaktylie" [Dominant Hereditary Acrocephalosyndactylia]. Zeitschrift für Kinderheilkunde (in German). 90: 301–20. PMID 14316612. doi:10.1007/BF00447500.
- Lerner, Maura (1997-03-28). "Prince's court case touches on 2 issues: A family's right to privacy, medical ethics". Star Tribune. Minneapolis – via NewsBank. (Subscription required (. ))
- Chanen, David (1997-06-14). "Ruling: Prince's baby died from natural causes". Star Tribune. Minneapolis – via NewsBank. (Subscription required (. ))
- Pelletiere, Nicole (2016-02-02). "Mom Defends Son Against Offensive Internet Meme". ABC News. Retrieved 2016-05-08.
- Hernandez, Vittorio (2016-02-05). "Texas mum mad at use of photo of son with rare disorder Pfeiffer syndrome to make cruel memes". International Business Times, Australia Edition. Retrieved 2016-05-08.
- "Mutter wehrt sich gegen Witze, die auf Kosten ihres kranken Sohnes gemacht werden" [Mother defends against jokes that are made at the expense of her sick son]. Stern (in German). 2016-02-08. Retrieved 2016-05-08.