Pfeiffer Syndrome

Clinical Characteristics

Ocular Features:

Patients may have extreme proptosis (95%) secondary to shallow orbits and exposure keratitis (41%) is a risk. Hypertelorism, strabismus, and antimongoloid lid slants are common. More rare signs include anterior chamber anomalies and optic nerve hypoplasia.

Systemic Features:

Pfeiffer syndrome has been divided into 3 types, of which cases with types 2 and 3 often die young. Type 1 has the more typical features with midface hypoplasia, broad thumbs and toes, craniosynostosis, and often some degree of syndactyly. Adult patients with type 1 may be only mildly affected with some degree of midface hypoplasia and minor broadening of the first digits. Hearing loss secondary to bony defects is relatively common. Cleft palate is uncommon. Airway malformations especially in the trachea can cause respiratory problems.

Genetics

This is a genetically heterogeneous disorder resulting from mutations in at least 2 genes, FGFR1 [1] (8p11.2-p11.1) and FGFR2 [2] (10q26). The less common cases with the latter mutation are allelic to Apert [3] (101200 [4]), Crouzon [5] (123500 [6]), and Jackson-Weiss [7] (123150 [8]) syndromes. Inheritance is autosomal dominant but some cases are only mildly affected. New mutations exhibit a paternal age effect.

Other forms of craniosynostosis in which mutations in FGFR2 [2] have been found are: Beare-Stevenson Syndrome [9] (123790 [10]), and Saethre-Chotzen Syndrome [11] (101400 [12]).

Treatment

Treatment Options:

Exposure keratitis requires the usual treatment. Fronto-orbital advancement surgery for the midface underdevelopment is generally helpful for the complications of proptosis. Airway obstruction may require tracheostomy or surgical correction of the air passages.

References

Article Title:

The ophthalmic sequelae of Pfeiffer syndrome and the long-term visual outcomes after craniofacial surgery [13]

Sharma N, Greenwell T, Hammerton M, David DJ, Selva D, Anderson PJ. The ophthalmic sequelae of Pfeiffer syndrome and the long-term visual outcomes after craniofacial surgery. J AAPOS. 2016 Jul 11. [Epub ahead of print].

PubMed ID:

27418250

Closing the Gap: Genetic and Genomic Continuum from Syndromic to Nonsyndromic Craniosynostoses [14]

Heuze Y, Holmes G, Peter I, Richtsmeier JT, Jabs EW. Closing the Gap: Genetic and Genomic Continuum from Syndromic to Nonsyndromic Craniosynostoses. Curr Genet Med Rep. 2014 Sep 1;2(3):135-145.

PubMed ID:

16146596

Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome [15]

Glaser RL, Jiang W, Boyadjiev SA, Tran AK, Zachary AA, Van Maldergem L, Johnson D, Walsh S, Oldridge M, Wall SA, Wilkie AO, Jabs EW. Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome. Am J Hum Genet. 2000 Mar;66(3):768-77.

PubMed ID:

10712195

Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome [16]

Schell U, Hehr A, Feldman GJ, Robin NH, Zackai EH, de Die-Smulders C, Viskochil DH, Stewart JM, Wolff G, Ohashi H, et al. Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome. Hum Mol Genet. 1995 Mar;4(3):323-8.

PubMed ID:

7795583

FGFR2 mutations in Pfeiffer syndrome [17]

Lajeunie E, Ma HW, Bonaventure J, Munnich A, Le Merrer M, Renier D. FGFR2 mutations in Pfeiffer syndrome. Nat Genet. 1995 Feb;9(2):108.

PubMed ID:

7719333