81 Pfeiffer Syndrome
Pfeiffer Syndrome 827
Acrocephalosyndactyly Type V, ACS V
Turribrachycephaly, midface hypoplasia, ocular prop- tosis, broad thumbs and halluces, syndactyly
Frequency: Rare.
Genetics
Autosomal dominant (OMIM 101600), intrafamilial variability; genetically heterogeneous: mutations of FGFR2 (fibroblast growth factor receptor-2) gene at 10q26 or FGFR1 at 8p11.2–p11.1.
Clinical Features
• Craniosynostosis
• Prominent forehead, flat facies
• Shallow orbits, proptosis, hypertelorism, strabis- mus, down-slanting palpebral fissures, flat nasal bridge, relative prognathism
• Low-set ears
• Broad thumb and great toe, with medial deviation, partial syndactyly of fingers 2–3 and toes 2–4
• Type 1: classic form
• Type 2: cloverleaf skull, severe CNS involvement, elbow ankylosis/synostosis
• Type 3: similar to type 2, without cloverleaf skull, severe proptosis, severe shortness of anterior cra- nial base
Differential Diagnosis
• Other craniosynostosis syndromes (Apert, Crouzon, Saethre-Chotzen, Jackson-Weiss)
Radiographic Features Skull
• Turribrachycephaly due to premature closure of the coronal sutures, with or without sagittal suture closure
• Shallow anterior cranial fossa
• Maxillary hypoplasia, with relative mandibular prognathism
• Hypertelorism
• Highly arched palate, broad alveolar ridges, crowded teeth
Hands and Feet
• Broad thumbs and great toes, usually with varus deformity
• Brachydactyly with brachymesophalangy
• Proximal symphalangism of thumb (with age)
• Broad 1st metatarsals (sometimes duplicated)
• Trapezoid or triangular (delta-shaped) proximal phalanges of thumb and great toe
• Soft tissue syndactyly of 2nd and 3rd fingers and 2nd, 3rd, and 4th toes
• Carpal and tarsal fusions Extremities
• Radioulnar synostosis
• Radiohumeral synostosis
• Short humerus
• Cubitus valgus Spine
• Cervical (most commonly C2–3) and lumbar fusions (70%)
• Kyphoscoliosis Pelvis
• Small iliac angle and iliac index
• Coxa valga
• Short femoral neck
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Pfeiffer Syndrome 828
Fig. 81.1 a, b. Patient 1, newborn. a Turricephaly, prominent forehead, midface deficiency, flat nasal bridge, and low-set ears. Note broad thumb on both hands. b Note broad great toe
and partial syndactyly of fingers 2 and 3. (Reprinted, with per- mission, from Canepa et al. 1996)
a b
Fig. 81.2 a, b. Patient 1, newborn. The skull is brachycephalic, with shallow anterior cranial fossa. Midfacial bones are hypo- plastic. (Reprinted, with permission, from Canepa et al. 1996)
a b
Bibliography
Canepa G, Maroteaux P, Pietrogrande V. Sindromi dismorfiche e malattie costituzionali dello scheletro. Piccin, Padova, 1996
Cohen MM. Pfeiffer syndrome update, clinical subtypes and guidelines for differential diagnosis. Am J Med Genet 1993;
45: 300–7
Cornejo-Roldan LR, Roessler E, Muenke M. Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syn- drome. Hum Genet 1999; 104: 425–31
Jabs EW. Toward understanding the pathogenesis of cran- iosynostosis through clinical and molecular correlates. Clin Genet 1998; 53: 79–86
Martsolf JT, Cracco JB, Carpenter GG, O’Hara AE. Pfeiffer syn- drome: an unusual type of acrocephalosyndactyly with broad thumbs and great toes. Am J Dis Child 1971; 121:
257–62
Plomp AS, Hamel BCJ, Cobben JM, Verloes A, Offermans JPM, Lajeunie E, Fryns JP, de Die Smulders CEM. Pfeiffer syn- drome type 2: further delineation and review of the litera- ture. Am J Med Genet 1998; 75: 245–51
Saldino RM, Steinbach HL, Epstein CJ. Familial acrocephalo- syndactyly (Pfeiffer syndrome). Am J Roentgenol 1972;
116: 609–22
Schaefer F, Anderson C, Can B, Say B. Novel mutation in the FGFR2 gene at the same codon as the Crouzon syndrome mutations in a severe Pfeiffer syndrome type 2 case. Am J Med Genet 1998; 75: 252–5
Schell U, Hehr A, Feldman GJ, Robin NH, Zackai EH, de Die- Smulders C, Viskochil DH, Stewart JM, Wolff G, Ohashi H, Price RA, Cohen MM, Muenke M. Mutations in FGFR1 and FGRF2 cause familial and sporadic Pfeiffer syndrome. Hum Mol Genet 1995; 4: 323–8
Pfeiffer Syndrome 829
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Fig. 81.3. aPatient 1, at birth. b Patient 1, at 5 months. The great toes are broad, with broad and deformed proximal and distal phalanges. There is partial soft tissue syndactyly of toes 2 and 3. (Reprinted, with permission, from Canepa et al. 1996)
a b
