Apert Syndrome is a rare congenital disorder that impacts the development of the skull, face, hands, and feet. It is primarily characterized by the premature fusion of the skull bones (craniosynostosis) and the fusion or webbing of the fingers and toes (syndactyly). These physical characteristics are present from birth and arise from a change in a single gene. The inheritance pattern is complex, involving both direct inheritance and spontaneous genetic events.
The Gene Responsible for Apert Syndrome
The underlying cause of Apert Syndrome is a mutation within the FGFR2 gene, located on chromosome 10. This gene provides instructions for creating the Fibroblast Growth Factor Receptor 2 protein. The FGFR2 protein acts as a receiver on cell surfaces, regulating cell growth, division, and differentiation, particularly in bone tissue.
The mutation causes the protein to become overactive, leading to faulty signaling. This overactivation tells bone cells to mature and fuse together too early during fetal development. Two specific missense mutations account for nearly all cases, resulting in the premature fusion of cranial sutures and bony structures of the hands and feet.
Understanding Autosomal Dominant Inheritance
Apert Syndrome follows an autosomal dominant inheritance pattern. This means a person only needs one copy of the altered FGFR2 gene to develop the condition. The term “autosomal” indicates the gene is located on a non-sex chromosome. An affected individual carries one functional copy of the gene and one altered copy.
When a parent has Apert Syndrome, they have a 50% chance of passing the altered gene copy to each child they conceive. This probability is the same for every pregnancy. If the child inherits the altered gene, they will develop the condition, as the functional copy cannot compensate for the mutated one. This 50% risk applies only when one parent is affected, and this direct inheritance accounts for a minority of all Apert Syndrome cases.
The Majority of Cases: Spontaneous Gene Mutation
Although the syndrome is transmitted in an autosomal dominant fashion, the vast majority of cases, estimated to be over 98%, are not inherited from a parent. These instances are the result of a de novo mutation, meaning the genetic change occurs spontaneously in the egg or sperm cell of an unaffected parent. This newly acquired mutation is present for the first time in the affected child and was not carried in the parents’ DNA.
The spontaneous change in the FGFR2 gene happens by chance during the formation of the reproductive cells. For a family with no prior history of the syndrome, the birth of a child with Apert Syndrome is usually a random, isolated event. This is why most affected children have parents who are genetically and phenotypically normal.
A notable factor in the occurrence of these new mutations is advanced paternal age. Research has shown that the risk of a de novo mutation in the FGFR2 gene increases significantly as the age of the father increases. This is likely due to the continuous divisions of sperm-producing cells over a man’s lifetime, which increases the opportunity for the spontaneous genetic error to occur. Since the mutation was not present in the parents’ own body cells, the recurrence risk for future children of the unaffected couple is negligible.
Genetic Testing and Counseling
Confirming a diagnosis of Apert Syndrome involves a combination of clinical features and molecular genetic testing. Genetic testing typically focuses on sequencing the FGFR2 gene to identify the specific mutation responsible for the condition. Identifying the exact mutation is important because it can distinguish Apert Syndrome from other similar craniofacial disorders.
Once a diagnosis is confirmed, genetic counseling plays a central role in helping families understand the implications of the genetic finding. A counselor will interpret the test results to determine if the mutation was inherited or occurred spontaneously. This distinction is critical for providing the family with accurate recurrence risk information for future pregnancies.
If the mutation is de novo, the parents can be reassured that the risk of having another affected child is very low. Conversely, if an affected parent is planning a family, the counselor will confirm the 50% transmission risk and discuss reproductive options, including prenatal testing. Prenatal diagnosis, such as amniocentesis or chorionic villus sampling, can be offered to families identified as being at increased risk.