The Apert hand is characterized by metaphyseal fusions of the metacarpals and distal phalanges, symphalangism, and soft-tissue syndactyly. More subtle skeletal anomalies of the limb characterize Pfeiffer and Crouzon syndromes. Different mutations in the fibroblast growth factor receptor 2 (FGFR2) gene cause these syndromes, and offer the opportunity to relate genotype to phenotype. The expression of FGFR1 and of the Bek and KGFR isoforms of FGFR2 has, therefore, been studied in human hand development at 12 weeks by in situ hybridization. FGFRs are differentially expressed in the mesenchyme and skeletal elements during endochondral ossification of the developing human hand. KGFR expression characterizes the metaphyseal periosteum and interphalangeal joints. FGFR1 is preferentially expressed in the diaphyses, whereas FGFR2-Bek expression characterizes metaphyseal and diaphyseal elements, and the interdigital mesenchyme. Apert metaphyseal synostosis and symphalangism reflect KGFR expression, which has independently been quantitatively related ex vivo to the severity of clinical digital presentations in these syndromes. Studies in avian development implicate FGF signaling in preventing interdigital apoptosis and maintaining the interdigital mesenchyme. Herein is proposed that in human FGFR syndromes the balance of signaling by means of KGFR and Bek in digital development determines the clinical severity of soft-tissue and bony syndactyly. (Plast. Reconstr. Surg. 107: 1331, 2001.)
Jonathan A. Britto, B.Sc., F.R.C.S.
The Craniofacial Centre
Level II, VCB
Great Ormond Street Hospital for Children
London, WC1N 3JH England
From the Craniofacial Centre, Great Ormond Street Hospital for Children, the Developmental Biology Unit, Institute of Child Health, and the Department of Orthodontics and Paediatric Dentistry, Guy's, King's and St. Thomas' Dental Institute, Guy's Hospital. Received for publication April 20, 2000; revised July 6, 2000.
Presented at the British Association of Plastic Surgeons Winter Meeting, in London, England, in December of 1999.