Carpenter Syndrome

What is Carpenter syndrome?

Carpenter syndrome is a rare inherited genetic disorder. Its main symptom is craniosynostosis, a congenital defect (meaning a person is born with it) that occurs when skull bones fuse (join) too early, before a baby’s brain fully forms.

As a baby with Carpenter syndrome grows, if those bones fuse too early, the skull can become misshapen (for example, pointed). That can cause asymmetrical facial features and a misshapen skull.

Carpenter syndrome also can cause deformities in the fingers and toes, as well as heart defects, hearing loss, intellectual disability and other issues.

The disorder is also called acrocephalopolysyndactyly, type II (ACPS II).

How common is Carpenter syndrome?

Carpenter syndrome is extremely rare. To date, experts have reported about 70 cases in medical literature.

What causes Carpenter syndrome?

Carpenter syndrome is an inherited genetic disorder that’s passed down through family members. It’s related to a mutation of one of two genes (RAB23 or MEGF8).

The RAB23 gene helps make a protein responsible for developing and shaping many parts of the body. Scientists aren’t sure about the role MEGF8 plays. And they’re not clear how these gene mutations cause the signs and symptoms of Carpenter syndrome.

How is Carpenter syndrome inherited?

Carpenter syndrome is an autosomal recessive disorder. This means that a child must inherit two copies of the abnormal gene, one from the mother and one from the father.

The parents often don’t have the disorder themselves, but they “carry” the mutated gene and pass it on.

If both biological parents are carriers of the mutation, then each child has a 25% risk of inheriting Carpenter syndrome.

What are the symptoms of Carpenter syndrome?

Signs of Carpenter syndrome usually start at birth or shortly afterward. They vary widely, even in people from the same family. Some people may have a few mild signs, but others may have severe disabilities.

The disorder can affect many parts of the body. Skeletal signs may include:

• Abnormal facial features (flat nose bridge, misshapen eyes or ears, or facial asymmetry, when the two sides look uneven).
• Congenital hand differences, such as webbed fingers or toes (syndactyly) or extra fingers or toes (polydactyly).
• Deformed hips.
• Dental abnormalities, such as small teeth or a jaw that hasn’t developed properly.
• Head that’s formed unusually, such as short and broad (brachycephaly), pointed (acrocephaly) or shaped like a cloverleaf.
• Knees angled inward.
• Rounded and curved upper back (kyphoscoliosis).

Other signs may include:

• Genital abnormalities, such as testes not moving into the proper position (undescended testicles).
• Hearing loss.
• Heart defects, such as atrial septal defect or ventricular septal defect (known as a hole in the heart).
• Intellectual disability, ranging from mild to severe.
• Obesity.
• Umbilical hernia (part of the intestine bulges through the belly button).
• Organs in the wrong position (for example, the heart on the right side of the body rather than the left).
• Vision problems.

How is Carpenter syndrome diagnosed?

A healthcare provider may suspect Carpenter syndrome based on a clinical exam and symptoms. They may order tests such as:

• CT scan or MRI to get pictures of the skull, heart, skeleton and organs.
• Electrocardiogram (EKG) or echocardiogram (echo) to evaluate the heart.
• Hearing tests.

The disorder is often misdiagnosed because it is rare and shares symptoms with other genetic disorders. Only molecular genetic screening of the RAB23 or MEGF8 gene can confirm the diagnosis. Genetic testing uses a sample of blood, hair, skin or other tissue.

If a family carries a Carpenter syndrome mutation, a healthcare provider may recommend preimplantation genetic testing or prenatal testing before birth. This may involve chorionic villus sampling, which tests a piece of placenta, or amniocentesis, which tests amniotic fluid (the liquid inside the uterus that surrounds a fetus). It also may involve prenatal ultrasound to take pictures of the fetus. Ultrasound can reveal:

• Abnormal head shape.
• Extra fingers or toes.
• Heart defects.
• Organs in the wrong positions.

How is Carpenter syndrome treated, and is there a cure?

There’s no cure for Carpenter syndrome. Treatment aims to:

• Correct skeletal abnormalities to improve appearance and reduce disability.
• Prevent complications from heart defects.

Treatments and therapies vary widely, depending on symptoms and their severity. Treatment may include surgery to:

• Close a hole in the heart.
• Prevent or correct premature closure of skull bones.
• Reduce pressure on the brain.
• Separate webbed fingers or toes or remove extra ones.
• Straighten the spine.

Your child may need a team of specialists, such as:

• Audiologists (hearing).
• Cardiologists (heart).
• Dental specialists.
• Neurologists (brain).
• Occupational therapists to help improve performance with daily activities, such as eating and writing.
• Ophthalmologists (vision).
• Orthopedists (joints, bones and spine).
• Physical therapists to improve strength and movement.
• Speech therapists.

How can I reduce the risk of Carpenter syndrome?

There’s no way to prevent the genetic mutation or avoid passing it to future generations unless a carrier couple were to undergo preimplantation genetic testing.

If you’re a carrier, your healthcare provider may recommend genetic counseling for you and other members of your family. The counselor will help you understand the risk involved for future children.

What can I expect if my child has this condition?

The outlook for a child with Carpenter syndrome depends on the severity of the disorder.

Some children with the disorder can become independent adults. But others need lifelong medical and social support for their physical and intellectual disabilities. Lifespan can be shorter because of heart defects.

What else can I ask my child’s healthcare provider about Carpenter syndrome?

If your child has Carpenter syndrome, consider asking your healthcare providers the following questions:

• Does my child have any heart defects?
• Could they be life-threatening?
• Can surgery correct the heart defect?
• Will my child have any intellectual disability?
• Could surgery on the skull reduce the chances of intellectual disability?
• Has the syndrome affected my child’s vision, hearing or dental development?
• What specialists should I see, and how often?
• Are there any support groups that can help us cope with this condition?
• Do you recommend genetic counseling for our situation?
• Should other people in our family get genetic testing?

A note from Cleveland Clinic

Carpenter syndrome is a rare inherited genetic disorder. In a baby with the condition, the skull bones fuse too early, before the brain fully forms. The disorder can also cause several physical and intellectual abnormalities, ranging from mild to severe. If your child has signs of Carpenter syndrome, talk to a healthcare provider about treatment options, support and genetic counseling.