Phenotype of the fibroblast growth factor receptor 2 Ser351Cys mutation: Pfeiffer syndrome type III.
We present a patient with pansynostosis, hydrocephalus, seizures, extreme proptosis with luxation of the eyes out of the lids, apnea and airway obstruction, intestinal non-rotation, and severe developmental delay. His skeletal abnormalities include bilateral elbow ankylosis, radial head dislocation, and unilateral broad and deviated first toe. The phenotype of this patient is consistent with that previously reported in Pfeiffer syndrome type III, but is unusual for the lack of broad thumbs. Our patient most closely resembles the case described by Kerr et al. [1996: Am J Med Genet 66:138-143] as Pfeiffer syndrome type III with normal thumbs. Mutations in the genes for fibroblast growth factor receptors (FGFR) 1 and 2 have previously been seen in patients with Pfeiffer syndrome type I. The mutation identified in our patient, Ser351Cys in FGFR2, represents the first reported cause of Pfeiffer syndrome type III. An identical mutation was described once previously by Pulleyn et al., in a patient whose brief clinical description included cloverleaf skull, significant developmental delay, and normal hands and feet [Eur. J. Hum. Genet. 4: 283-291, 1996]. In our patient, previously performed single-strand conformation polymorphism analysis failed to detect a band shift; the mutation was identified only after independent sequence analysis.
Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
K W
KW
Gripp
C A
CA
Stolle
D M
DM
McDonald-McGinn
R I
RI
Markowitz
S P
SP
Bartlett
J A
JA
Katowitz
M
M
Muenke
E H
EH
Zackai
D000015:Abnormalities, Multiple / Q000235:genetics*; D000168:Acrocephalosyndactylia / Q000000981:diagnostic imaging / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D004550:Elbow / Q000002:abnormalities / Q000000981:diagnostic imaging; D005124:Eye Abnormalities / Q000235:genetics; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011859:Radiography; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012694:Serine / Q000235:genetics; D014178:Translocation, Genetic; D014910:Wheelchairs
D017468:Receptors, Fibroblast Growth Factor; D012694:Serine; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D003545:Cysteine