Pfeiffer syndrome

Pfeiffer syndrome (also known as Acrocephalosyndactyly type 5, ACS5) is one of the craniosynostoses.

Clinically, 3 types of Pfeiffer syndrome are distinguished:

• Type 1 (classic Pfeiffer syndrome): the synostosis usually affects the coronal suture with brachycephaly, midface hypoplasia, hypertelorism, exophthalmos and mandibular prognathism. Typical features are widened thumbs and big toes with radial or tibial deviation and sometimes proximal membranous syndactyly. Intelligence is usually not impaired.
• Type 2: characterized by a cloverleaf skull with hand and foot malformations similar to type 1.
• Type 3: similar phenotype to type 2, but without the cloverleaf skull.

Type 1 usually occurs in families with complete penetrance and variable expressivity. Types 2 and 3 are more common than type 1 and always occur sporadically; patients are always more severely affected than in type 1 and life expectancy is significantly reduced.

The exact frequency of Pfeiffer syndrome is not known, but it is significantly rarer than Apert or Crouzon syndrome. Pfeiffer syndrome is caused by pathogenic variants in the FGFR1 and FGFR2 genes: subtypes 2 and 3 are always caused by pathogenic variants in FGFR2, while 95% of subtype 1 is caused by pathogenic variants in FGFR2.

References

Wenger et al. 2017, Genet Med 19:62 / Bessenyei et al. 2014, Am J Med Genet A 164A:3176 / Seto et al. 2007, Am J Med Genet 143A:678 / Vogels and Fryns 2006, Orphanet J Rare Dis 1:19 / Kress et al. 2006, Eur J Hum Genet 14:39 / Wilkie et al. 2002, Am J Med Genet 112:266 / Schell et al. 1995, Hum Molec Genet 4:323 / Muenke et al. 1994, Nature Genet 8:269