Carpenter syndrome

Carpenter syndrome (ACPS II) is a rare genetic disorder with symptoms that are present at birth. One of a group of disorders known as acrocephalopolysyndactyly, it results in early closure of the skull sutures (joints between the bones of the skull), webbed toes, and webbed fingers. It cannot be cured and treatment is directed towards managing symptoms.

Definition & Facts

Carpenter syndrome has been recognized since 1901 but was not considered a distinct disease entity until 1966. In addition to its effects on the skull sutures and digits, it may result in skeletal deformities or facial malformations. The condition may be accompanied by other conditions such as short stature, congenital heart defects, obesity, and mild to moderate intellectual disabilities. However, some children have normal intelligence.

Carpenter syndrome is caused by genetic mutations, specifically in the RAB23 gene (Carpenter syndrome type I) and the MEGF8 gene (Carpenter syndrome type II). It is a recessive condition, which means the child must inherit a genetic mutation from each parent.

Related disorders include Pfeiffer syndrome, Goodman syndrome, Apert syndrome, Crouzon syndrome, Saethre-Chotzen syndrome, Summit syndrome, and Greig cephalopolysyndactyly. All of these conditions are very rare.

Symptoms & Complaints

Fingers and toes may be excessively short due to missing bones and are partly fused together with webs between the digits. The third and fourth digits are most likely to be fused. Occasionally, children with Carpenter syndrome will have extra fingers or toes. Other congenital conditions such as heart defects may accompany Carpenter syndrome.

Symptoms and severity of the condition often vary considerably from one patient to another, even if they are closely related. There are often few differences between the symptoms of Carpenter syndrome type 1 and 2, and only genetic testing can determine which type exists in a particular patient.

An abnormal skull shape due to early closure of the skull sutures is nearly always present. If the skull is badly deformed, it may lead to increased pressure inside the skull. In addition to other symptoms, children with Carpenter syndrome may have visual disturbances due to damage to the optic nerve or the eye itself. They may also have hearing problems or speech problems.

Causes

Although the cause of Carpenter syndrome is known to be due to genetic mutations, the condition is so rare that is has been little studied. Approximately 70 cases of Carpenter syndrome have been documented. Children born to parents of Northern European descent have a higher risk than those of other ethic groups.

In addition, children in the same family with identical gene mutations may have distinctly different symptoms and/or the severity of the symptoms may be different. Since Carpenter syndrome is a recessive trait, both parents must carry mutated genes in order for a child to develop the disorder. In a few cases, however, neither the RAB23 gene nor the MEGF8 gene in a child with Carpenter syndrome show any evidence of mutation.

If each parent carries the genetic mutation, the odds of a child developing Carpenter syndrome are 25 percent, but the odds of a child becoming a carrier are 50 percent. A child born to parents who are more closely related, such as cousins, has a higher risk of the disorder due to the partners' shared genetic background and common ancestry.

Diagnosis & Tests

In some cases, Carpenter syndrome may be diagnosed before birth through the use of ultrasound or fetoscopy. Fetoscopy is the insertion of a small catheter into the uterus which allows the fetus to be visualized with a special camera. Fetoscopy also allows the physician to obtain blood tests or tissue samples.

Genetic testing of those samples may show the genetic mutations. In most cases the diagnosis is made after birth. A thorough physical examination can help identify the characteristic clinical findings such as head shape, early closure of skull sutures and facial deformities, or webbing and fusion of fingers and toes.

Imaging techniques such as computed tomography (CT) scans and magnetic resonance imaging (MRI) can also identify skeletal deformities or evidence of the disorder in internal organs. Heart abnormalities are often identified through specialized tests like an electrocardiogram or echocardiogram.

Treatment & Therapy

As a genetic disorder, Carpenter syndrome cannot be cured. Symptoms must be treated and/or managed. All treatments are symptomatic and supportive. For example, early closure of the skull sutures may increase pressure inside the skull, and surgery is often necessary to correct the condition. Surgery may also help correct facial deformities and may be required for some heart conditions.

Hearing aids, glasses, and speech therapy can be beneficial if children show evidence of problems in these areas. In all cases, early intervention is vitally important. In addition to symptom-related treatments, special education, physical therapy, and social or vocational services may be required.

Genetic counseling is usually recommended for both patients and their families. Siblings may be carriers of Carpenter syndrome and should understand the risk of having their own children. Parents and siblings may also have subtle symptoms or physical characteristics of Carpenter syndrome and should be evaluated for possible treatment. Psychosocial support and counseling are usually important for the whole family.

Prevention & Prophylaxis

In a few cases, Carpenter syndrome has occurred in the absence of characteristic genetic mutations, so there is no guarantee of preventing the condition even with preconception genetic testing. However, genetic testing can serve to identify carriers, which gives potential parents the option to assess the risk and weigh the costs and benefits.