Apert syndrome is a rare congenital disorder characterized by the premature fusion of bone structures, primarily affecting the skull and limbs. It is defined by the presence of craniosynostosis and syndactyly, which are observable physical features present at birth. Diagnosis moves from initial physical observation to detailed internal imaging, concluding with definitive molecular confirmation.
Recognizing Initial Clinical Indicators
The diagnostic process begins immediately after birth with a thorough physical examination. Three distinct physical characteristics suggest Apert syndrome, prompting further testing. The first is craniosynostosis, the premature closure of cranial sutures, especially the coronal sutures. This early fusion prevents normal skull growth, often resulting in a distinctive “tower skull” appearance, known as turribrachycephaly, with a high, prominent forehead.
The second feature is midface hypoplasia, an underdeveloped middle section of the face. This causes a depressed nasal bridge and shallow orbits, making the eyes appear prominent or bulging. This facial structure helps differentiate Apert syndrome from other forms of craniosynostosis. The third distinguishing sign is bilateral and symmetrical syndactyly, the fusion or webbing of the fingers and toes.
This fusion typically involves the second, third, and fourth digits of the hands and feet, resulting in the characteristic appearance of “mitten hands” or “sock feet.” Fusion ranges from soft tissue webbing to complete bony union, known as osseous syndactyly. The simultaneous presence of these anomalies serves as the initial clinical evidence guiding confirmation.
Structural Confirmation Through Imaging Studies
Once clinical signs suggest Apert syndrome, imaging studies confirm the extent of skeletal abnormalities. Standard X-rays are the first step, visualizing the bony structure of the hands, feet, and skull. X-rays demonstrate syndactyly, showing the specific bones fused in the digits.
X-rays also offer initial evidence of craniosynostosis, revealing prematurely closed coronal sutures and the altered cranial vault shape. A Computed Tomography (CT) scan is the most informative modality for structural confirmation, providing detailed, three-dimensional views of the skeleton. The CT scan is essential for precisely mapping the extent of skull base and suture fusion, which is important for surgical planning.
A 3D CT scan confirms bilateral coronal synostosis and details the severity of midface hypoplasia and shallow eye orbits. Scans also detect associated abnormalities, such as the “copper-beaten” appearance on the inner skull surface, suggesting increased intracranial pressure. CT imaging allows for precise assessment of carpal and tarsal bone fusions in the wrists and ankles.
The detailed structural information from the CT scan confirms the full spectrum of skeletal dysmorphology. This objective proof of bony malformations moves the diagnosis beyond clinical suspicion. Imaging results are subsequently used to guide specialized surgical interventions.
Definitive Genetic Analysis
While clinical presentation and imaging suggest the diagnosis, definitive confirmation relies on molecular genetic analysis. Apert syndrome is caused by specific mutations in the FGFR2 gene, which provides instructions for the Fibroblast Growth Factor Receptor 2 protein. The FGFR2 gene is located on chromosome 10 and regulates bone growth and differentiation.
The associated mutations cause the FGFR2 protein to be overactive, resulting in a gain-of-function that promotes premature bone fusion. Over 98% of cases are caused by one of two specific substitutions: Ser252Trp or Pro253Arg. These mutations drive the early closure of cranial sutures and the fusion of bones in the hands and feet.
Genetic testing is performed using a blood sample, from which DNA is extracted and analyzed, often through Next-Generation Sequencing (NGS). This process identifies the specific pathogenic variant in the FGFR2 gene. Confirmation of this genetic mutation is the most conclusive diagnostic step.
This genetic confirmation differentiates Apert syndrome from other craniosynostosis syndromes, such as Crouzon or Pfeiffer syndromes, that have similar clinical features. A confirmed genetic diagnosis is important for providing accurate genetic counseling to the family. Although most cases result from a spontaneous, new mutation, identifying the specific variant allows for a clear understanding of the condition’s cause and potential recurrence risks. This molecular confirmation completes the diagnostic journey and provides a foundation for developing a specialized treatment plan.