What is Apert Syndrome?

Apert syndrome is a genetic condition that causes early fusion of certain skull bones (a condition known as craniosynostosis), resulting in abnormalities of the face and skull. It also leads to the fusing of fingers or toes (syndactyly). The syndrome was first identified in 1906 by a French doctor named Eugene Apert, who discovered nine people showing similar facial and hand/foot features.

What Causes Apert Syndrome?

Apert syndrome is a condition passed down through families that affects the growth of the skull. It’s caused by specific changes in a factor that promotes cell growth, named fibroblast growth factor receptor 2 (FGFR2). This is located on a specific section of our DNA, chromosome 10q.

Risk Factors and Frequency for Apert Syndrome

Apert syndrome is uncommon, showing up in about 1 out of every 65,000 to 200,000 births depending on the study. It doesn’t favor any gender – males and females are equally likely to have it. The chance of getting the syndrome increases as the father’s age increases. Even if the condition is fully inherited (which means it always shows up in those who carry the genes), it can show differently in different people. This means that relatives in the same family can range from not showing any signs of the disease to having severe deformities.

Signs and Symptoms of Apert Syndrome

Apert syndrome is a genetic disorder that’s passed down from parents to their children. If someone in your family has Apert syndrome, you’re more likely to have it. However, even if there’s no family history, the syndrome can still occur due to random genetic mutations.

The syndrome is associated with a range of physical features. People with Apert syndrome may have a particular shape of the head and face, resulting from premature fusion of the skull bones. This is more severe than the similar condition known as Crouzon syndrome, and the presence of fused fingers and/or toes (syndactyly) also helps to differentiate Apert syndrome. Common facial features include eyes that are set wide apart (hypertelorism), protruding eyes (proptosis), and eyelid slits that point downwards.

Specific characteristics of the hands in Apert syndrome include a short thumb that deviates towards the radius (the forearm bone on the thumb side), fusion of several fingers, and stiff fingers due to bones not separating fully in the womb (symphalangism). The syndrome presents three distinct subtypes based on the overall shape of the hand, referred to as “spade” (for a flat palm and side-by-side finger fusion), “mitten” (for fingers fused in a way that causes a concave palm), and “rosebud” (for tight fusion of all fingers).

Other symptoms can include craniofacial deformities such as abnormal head shape, protruding eyes, a prominent forehead, a flattened bridge of the nose, and dental abnormalities such as crowded teeth, high-arched palate, narrow palate, and pseudo-clefts. The syndrome may also cause abnormalities in internal organs and the skeleton, like cervical fusions. Cognitive disability, ranging from mild to moderate, is also a possibility.

Testing for Apert Syndrome

If a family has a history of Apert syndrome, the diagnosis can often be confirmed through a simple physical examination. However, in cases where no family history exists or the symptoms are not clear, other tests may be needed. These could include advanced imaging techniques such as magnetic resonance imaging (MRI) or computed tomography (CT) scans. These scans can detect craniosynostosis, a condition where the bones in a baby’s skull fuse too early, or other bone abnormalities. They can also help to spot complications that could arise from the syndrome, like elevated pressure inside the skull.

In situations where the diagnosis is uncertain or the syndrome presents odd features, similar to Crouzon syndrome, genetic and molecular tests might be necessary. These syndromes often happen due to mutations in the FGFR genes and unusual signaling activity. If Apert syndrome is suspected before a child is born, prenatal genetic testing, MRI, and ultrasounds can help to confirm the diagnosis. Procedures like amniocentesis or sampling of the chorionic villus may be done, but advancements in safer imaging techniques are making these high-risk procedures less and less necessary, except in the most challenging cases.

While physical examinations, patient history, and imaging can typically verify the specific type of craniosynostosis, this can be difficult due to significant similarities among various syndromes like Pfeiffer, Apert, Saether-Chotzen, Carpenter, and Jackson-Weiss syndromes.

Treatment Options for Apert Syndrome

Apert syndrome, like other craniosynostoses (conditions where one or more of the joints in the skull fuse prematurely), is managed by a team of multiple specialists. This can include pediatricians, neurosurgeons, plastic surgeons, craniofacial surgeons, ophthalmologists, and dentists. They work together to prevent the complete closure of the coronal suture, which is the joint running from ear to ear on the skull, to protect brain development. This usually requires surgery.

The details of the surgical process can be found in the guidelines from the “Working Group on Craniosynostosis.” The approach is similar to that taken with Crouzon syndrome, another craniosynostosis condition. It is generally believed that performing surgery before the child turns one leads to better long-term outcomes. However, this idea is based more on observations rather than extensive controlled trials. Similarly, there’s no standard treatment for syndactyly, a condition where the fingers are fused together, but it’s likely that multiple surgeries will be needed as the child grows.

Long-term check-ups are crucial to minimize the risk of complications related to craniosynostosis, such as eye misalignment, sleep apnea, and increased pressure within the skull. These issues may not be completely solved with surgery correcting the facial and skull defects. According to one study, 54% of patients suffered from vision loss in at least one eye due to amblyopia (a vision development disorder) that occurred after surgery. That said, early surgeries have led to a low rate (5%) of optic atrophy, which is the severe loss of nerve fibers in the eye. Misalignment of the eyes and severe hearing loss are also common occurrences.

Therefore, a collaborative approach involving several specialists is crucial to monitor the development of this condition, as it can lead to vision impairments and potentially life-threatening complications. It also helps in deciding the best time and method to perform surgery.

Studies are currently underway in laboratories to develop chemical inhibitors that could potentially restore normal FGFR signaling in the body and correct the skeletal defects associated with these conditions.

When a doctor tries to diagnose Apert syndrome, they must consider other conditions that can present similar symptoms. These conditions include:

Achondroplasia (a form of short-limbed dwarfism)
Antley-Bixler syndrome (a disorder affecting physical development)
Beare-Stevenson syndrome (a condition that affects skin, skull, and facial features)
Disorders arising from changes in the genes for fibroblast growth factor receptors
Crouzon syndrome (a condition affecting the shape of the head and face)
Cutis gyrata (a condition where the skin has a wrinkled appearance)
Pfeiffer syndrome (a condition affecting the shape of the skull and face)
Thanatophoric dysplasia (a severe form of dwarfism)

Each of these conditions comes with its own distinct set of symptoms, but there can be overlaps that make diagnosis challenging. Therefore, the doctor needs to take all possibilities into account and use different tests to come to the correct diagnosis.

What to expect with Apert Syndrome

The outlook depends on the timing of the surgery and the specific medical conditions that required the surgical procedure.

Possible Complications When Diagnosed with Apert Syndrome

People with Apert syndrome may face several health problems, including:

Raised pressure inside the skull, leading to swelling of the optic nerve and issues with cognitive functions
Eye problems, including corneal scarring and exposure keratopathy, a disease affecting the outer layer of the eye
Breathing-related complications
Spinal cord injuries and nervous system disorders, specifically in those with abnormal neck bones
Pneumonia caused by inhaling food or liquid (aspiration pneumonia), eventually causing further chronic lung disease

Preventing Apert Syndrome

Apert syndrome is a condition that’s inherited in a pattern known as autosomal dominant. This means it can be passed down from parents to their children. A key factor related to this condition is the advanced age of the father, which can cause the syndrome to appear even if there was no prior family history of it. If someone in the family has this gene variation that causes Apert syndrome, there is a 50% chance they could pass it on to each of their children.

If a family member is known to carry this gene variation, it’s recommended that prenatal testing be done during pregnancies that are at a higher risk. This can help detect the syndrome early and prepare for any potential health challenges.