three isoforms of FGFR2, the gene with the point mutations that causes the syndrome in 98% of the patients. KGFR, keratinocyte growth factor receptor, is an isoform active in the metaphysis and interphalangeal joints. FGFR1 is an isoform active in the diaphysis. FGFR2-Bek is active in the metaphysis, as well as the diaphysis, but also in the interdigital mesenchyme. The point mutation increases the ligand-dependent activation of FGFR2 and thus of its isoforms. This means that FGFR2 loses its specificity, causing binding of FGFs that normally do not bind to the receptor. Since FGF suppresses apoptosis, the interdigital mesenchyme is maintained. FGF also increases replication and differentiation of osteoblasts, thus early fusion of several sutures of the skull. This may explain why both symptoms are always found in Apert syndrome. Diagnosis Diagnosis is typically by the apparent physical characteristics and can be aided by skull X-ray or head CT examination. Molecular genetic testing can confirm the diagnosis. Treatments Craniosynostosis Surgery is needed to prevent the closing of the coronal sutures from damaging brain development. In particular, surgeries for the LeFort III or monobloc midface distraction osteogenesis which detaches the midface or the entire upper face, respectively, from the rest of the skull, are performed in order to reposition them in the correct plane. These surgeries are performed by both plastic and oral and maxillofacial (OMS) surgeons, often in collaboration. Syndactyly There is no standard treatment for the hand malformations in Apert due to the differences and severity in clinical manifestations in different patients. Every patient should therefore be individually approached and treated, aiming at an adequate balance between hand functionality and aesthetics. However, some guidelines can be given depending on the severity of the deformities. In general it is initially recommended to release the first and fourth interdigital spaces, thus releasing the border rays. This makes it possible for the child to grasp things by hand, a very important function for the child's development. Later the second and third interdigital spaces have to be released. Because there are three handtypes in Apert, all with their own deformities, they all need a different approach regarding their treatment: Type I hand usually needs only the interdigital web space release. First web release is rarely needed but often its deepening is necessary. Thumb clinodactyly correction will be needed. In type II hands it is recommended to release the first and fifth rays in