Carpenter syndrome

December 31, 2014

Synonyms

Overview

Carpenter syndrome is a condition characterized by premature fusion of skull bones (craniosynostosis); finger and toe abnormalities; and other developmental problems. The features in affected people vary. Craniosynostosis can give the head a pointed appearance; cause asymmetry of the head and face; affect the development of the brain; and cause characteristic facial features. Other signs and symptoms may include dental abnormalities; vision problems; hearing loss; heart defects; genital abnormalities; obesity; various skeletal abnormalities; and a range of intellectual disability. Carpenter syndrome can be caused by mutations in the RAB23 or MEGF8 gene and is inherited in an autosomal recessive manner.

Symptoms

The signs and symptoms of Carpenter syndrome can vary greatly, even within members of the same family. The main features include premature closure of certain skull bones (craniosynostosis), distinctive facial characteristics, and/or abnormalities of the fingers and toes (digits). People with Carpenter syndrome often have intellectual disability (from mild to profound), but some affected people have normal intelligence.

Craniosynostosis prevents the skull from growing normally, frequently giving the head a pointed appearance (acrocephaly). In severely affected individuals, the abnormal fusion of the skull bones results in a deformity called a cloverleaf skull. Craniosynostosis can cause differences between the two sides of the head and face (craniofacial asymmetry). Early fusion of the skull bones can affect the development of the brain and lead to increased pressure within the skull (intracranial pressure). Premature fusion of the skull bones can cause several characteristic facial features in people with Carpenter syndrome. Distinctive facial features may include a flat nasal bridge, outside corners of the eyes that point downward (down-slanting palpebral fissures), low-set and abnormally shaped ears, underdeveloped upper and lower jaws, and abnormal eye shape. Some affected individuals also have dental abnormalities including small primary (baby) teeth. Vision problems also frequently occur.

Abnormalities of the fingers and toes include fusion of the skin between two or more fingers or toes (cutaneous syndactyly), unusually short fingers or toes (brachydactyly), or extra fingers or toes (polydactyly). In Carpenter syndrome, cutaneous syndactyly is most common between the third (middle) and fourth (ring) fingers, and polydactyly frequently occurs next to the big or second toe or the fifth (pinky) finger.

People with Carpenter syndrome often have intellectual disability, which can range from mild to profound. However, some individuals with this condition have normal intelligence. The cause of intellectual disability is unknown, as the severity of craniosynostosis does not appear to be related to the severity of intellectual disability.

Other features of Carpenter syndrome include obesity that begins in childhood, a soft out-pouching around the belly-button (umbilical hernia), hearing loss, and heart defects. Additional skeletal abnormalities such as deformed hips, a rounded upper back that also curves to the side (kyphoscoliosis), and knees that are angled inward (genu valgum) frequently occur. Nearly all affected males have genital abnormalities, most frequently undescended testes (cryptorchidism).

Causes

Mutations in the RAB23 or MEGF8 gene cause Carpenter syndrome.

The RAB23 gene provides instructions for making a protein that is involved in a process called vesicle trafficking, which moves proteins and other molecules within cells in sac-like structures called vesicles. The Rab23 protein transports vesicles from the cell membrane to their proper location inside the cell. Vesicle trafficking is important for the transport of materials that are needed to trigger signaling during development. For example, the Rab23 protein regulates a developmental pathway called the hedgehog signaling pathway that is critical in cell growth (proliferation), cell specialization, and the normal shaping (patterning) of many parts of the body.

The MEGF8 gene provides instructions for making a protein whose function is unclear. Based on its structure, the Megf8 protein may be involved in cell processes such as sticking cells together (cell adhesion) and helping proteins interact with each other. Researchers also suspect that the Megf8 protein plays a role in normal body patterning.

Mutations in the RAB23 or MEGF8 gene lead to the production of proteins with little or no function. It is unclear how disruptions in protein function lead to the features of Carpenter syndrome, but it is likely that interference with normal body patterning plays a role. For reasons that are unknown, people with MEGF8gene mutations are more likely to have dextrocardia and other organ positioning abnormalities and less severe craniosynostosis than individuals with RAB23 gene mutations.

Diagnosis

The phrase "signs of Carpenter syndrome" should, strictly speaking, refer only to those signs and symptoms of Carpenter syndrome that are not readily apparent to the patient. The word "symptoms of Carpenter syndrome" is the more general meaning; see symptoms of Carpenter syndrome. The signs and symptom information on this page attempts to provide a list of some possible signs and symptoms of Carpenter syndrome. This medical information about signs and symptoms for Carpenter syndrome has been gathered from various sources, may not be fully accurate, and may not be the full list of Carpenter syndrome signs or Carpenter syndrome symptoms. Furthermore, signs and symptoms of Carpenter syndrome may vary on an individual basis for each patient. Only your doctor can provide adequate diagnosis of any signs or symptoms and whether they are indeed Carpenter syndrome symptoms.

Treatment

Treatment focuses on the specific features in each affected person. Life expectancy is shortened but very variable.