Rare Genetic Diseases: Carpenter Syndrome

Carpenter syndrome, also known as acrocephalopolysyndactyly type 2, only occurred in approximately 70 individuals. Now, many of you might think that it is impossible to understand the principles and symptoms of this disease, since only a few cases have been described in the scientific literature, but over the years, more information, than expected, has been discovered.

Carpenter syndrome (CS) is an autosomal recessive disorder which is characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental issues. The craniosynostosis causes the head to appear pointed (acrocephaly). Not only does the fusion of the skull bones affect the shape of the head, it also leads to increased pressure within the skull (intracranial pressure) and therefore disturbs the development of the brain.

CS causes two distinct abnormalities of the fingers and toes which include fusion of the skin between two or more fingers or toes (cutaneous syndactyly) and extra fingers or toes (polydactyly). Genetic testing is often required for correct diagnosis as CS has overlapping syndromes with Greig cephalopolysyndactyly syndrome.

Few of the individuals suffering from CS have mirror-image reversed positions of the organs or tissues located in their abdomen or their chest. This symptom may appear in three different locations:

1. Situs inversus — affecting several internal organs such as the liver or stomach
2. Dextrocardia — affects just the heart, placing it on the right side of the body instead of left
3. Affecting the major arteries of the heart, altering the blood flow

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. There are two known genetic mutations that are causing CS. The first one is located on the MEFG8 gene, and unfortunately not much is known about this mutation apart from the fact that the gene provides instructions for making a protein whose function has not been established.

The second mutation is located on the RAB23 gene which provides instructions for making a protein that is involved in a process called vesicle trafficking. The process is characterized by specific movement of proteins and other molecules within cells. The RAB23 gene regulates a developmental pathway called the hedgehog signaling pathway that is critical in cell growth (proliferation) and normal shaping (patterning) of many parts of the body.

The life expectancy of individuals suffering from Carpenter syndrome is significantly shortened, however, it varies from patient to patient.