Carpenter syndrome
Carpenter syndrome is a rare genetic disorder inherited in an autosomal recessive manner, primarily characterized by craniosynostosis, which is the early closure of skull sutures, leading to distinct head shapes. Individuals with this syndrome may also experience webbing or fusion of fingers and toes, extra digits, and congenital heart defects. First identified in the early 20th century, the syndrome is linked to mutations in the RAB23 gene located on chromosome 6, which affects cell signaling crucial for proper development.
Symptoms often include facial malformations, developmental delays, and short stature, along with potential vision problems and hernias. Diagnosis typically relies on physical examination and imaging techniques such as X-rays or CT scans, as there is no specific test for the syndrome. Treatment is varied and may involve multiple surgeries to address skull malformations and associated health issues, with ongoing care for related concerns like vision and dental health. While there is no known prevention for Carpenter syndrome, timely medical interventions can significantly improve outcomes and quality of life for individuals affected by the condition.
Carpenter syndrome
ALSO KNOWN AS: Acrocephalopolysyndactyly type II; ACPS II
DEFINITION: Carpenter syndrome is a rare genetic disorder that is inherited in an autosomal recessive manner. The disorder is characterized by craniosynostosis (early closure of the cranial sutures of the skull), webbing of certain fingers or toes and/or more than the normal number of fingers or toes, and sometimes congenital heart defects.
Risk Factors
It is not known whether particular risk factors lead to Carpenter syndrome. However, since the disorder is inherited in an autosomal recessive manner, a person will develop it if both parents are carriers of the defective RAB23 gene. Both men and women have been diagnosed with Carpenter syndrome.
Etiology and Genetics
Carpenter syndrome was first identified in the early 1900s by George Carpenter. The disorder belongs to a group of rare genetic disorders known as acrocephalopolysyndactyly, which are characterized by craniosynostosis, webbing or fusion of digits, and more than the normal number of digits. Carpenter syndrome is a pleiotropic disorder, meaning that a single gene influences multiple phenotypic traits. Because it is inherited in an autosomal recessive manner, a person who shows the symptoms of the syndrome must carry two mutant genes (one inherited from each parent).
While the molecular basis of many craniosynostosis syndromes had been discovered, the cause of Carpenter syndrome was unknown until recently. The disorder is rare and estimated to occur in less than one out of every one million live births. As of 2024, only about seventy cases had been documented in scientific literature. In 2007, scientists found linkage of Carpenter syndrome to chromosome 6, more specifically the RAB23 gene. In fifteen independent families with Carpenter syndrome, five different RAB23mutations were identified, four of which were truncating (when a codon for one amino acid is changed into a stop codon) and one missense (when a codon for one amino acid is changed into a codon for another amino acid).
The RAB23 gene encodes a member of the RAB guanosine triphosphatase (RAB GTPase) family of vesicle transport proteins and acts as a negative regulator of hedgehog (HH) signaling. The HH signaling pathway provides cells with the information that they need to develop properly; cells develop differently based on where they are in the embryo and eventually become part of different body parts. The discovery of RAB23 mutations in patients with Carpenter syndrome did not surprise scientists, since other disorders associated with faulty HH signaling share some of the same physical characteristics as Carpenter syndrome, especially regarding superfluous, webbed, or shortened digits. However, researchers were surprised that finding RAB23 mutations in those with Carpenter syndrome implies that HH signaling is involved in cranial sutures. There is much left to learn about HH signaling and craniosynostosis in Carpenter syndrome.
Symptoms
The most common physical symptom of Carpenter syndrome is craniosynostosis, leading to either a short and broad head or a cone-shaped head (acrocephaly). Facial malformations are also usually present in those with Carpenter syndrome, as are digit abnormalities (webbing or fusion, extra digits, and/or shortened digits). Individuals with Carpenter syndrome may also have congenital heart defects, vision problems, hernias, undescended testes (in males), developmental delays, and a highly arched and narrow palate. They may be of short stature and tend toward obesity.
Screening and Diagnosis
There is no specific way to test for Carpenter syndrome, but the disorder may be ruled out as a diagnosis if a suspected patient tests positive for another genetic disorder that also has skull malformations. Diagnosis is usually made based on the skull malformations observed at birth, along with the presence of other Carpenter syndrome symptoms. X-rays and CT scans may be key in ensuring that a Carpenter syndrome diagnosis is correct.
An ultrasound anatomy scan can be performed during pregnancy to look at skull development. If deformities are noticed, however, it may not always be possible to distinguish between Carpenter syndrome and other potential causes.
Treatment and Therapy
Treatment for Carpenter syndrome varies for each individual. Usually, the most crucial and immediate surgical interventions correct skull malformations during the first year of life in order to create room for the rapidly growing brain. Several procedures may be necessary. If serious heart defects like a hole in the heart are present, then heart surgery may also be necessary shortly after birth. Surgery to straighten the spine may be required as well.
Hand and foot reconstruction, jaw surgery, and surgery to move undescended testes may also be part of the treatment plan for Carpenter syndrome-affected individuals. Diet, vision, and the highly arched and narrow palate of those with Carpenter syndrome may also need to be addressed. In addition, some children with Carpenter syndrome may need to seek specialized treatment from audiologists, opthamologists, or dentists.
Prevention and Outcomes
There is no effective means of prevention for Carpenter syndrome. If the skull malformations and heart defects associated with Carpenter syndrome are treated appropriately and promptly, however, then affected individuals will live and benefit from an improved physical appearance following surgical intervention. Vision problems and developmental delay may persist, but many of the symptoms of Carpenter syndrome can be treated and greatly diminished.
Bibliography
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