What Is Carpenter Syndrome?

Overview

Carpenter syndrome (CS) is a congenital group of genetic disorders, categorised as Acrocephalopolysyndactyly(ACPS) type 2 disorder. It involves developmental abnormalities of the skull, webbing of fingers and toes, premature fusion of one or more cranial sutures, an abnormal conical skull, and other defects.

About 70 CS cases are listed in the literature to date.¹ CS was first identified in two sisters and a brother in 1901 but was not recognised as a recognisable disease until 1966.⁴

The causes of carpenter syndrome

CS primarily develop from mutations in the RAB23 gene, situated on chromosome 6. These mutations disturb protein production, affect many bodily functions, and impact the brain. Sometimes, the MEGF8 gene mutation causes Carpenter syndrome. These genetic mutations are inherited in an autosomal recessive pattern, which means that an individual requires two abnormal gene copies - one from each parent - to manifest Carpenter syndrome. If an individual inherits one abnormal gene, they become carriers without exhibiting symptoms. The risk of two carrier parents having an affected child is 25% per pregnancy, and the risk of having a carrier child is 50%. Unrelated parents have a lower risk of carrying the same abnormal gene. Both males and females have equal risks.³

Signs and symptoms

The effects of CS may occur at different ages (Before birth, at birth- 4 weeks, and at 2-11 years).⁴ The symptoms may vary even among people of the same family: Some have mild disorders, and others are severely affected.⁵

1. Craniofacial defects
   • Acrocephaly: The top portion of the skull appears conical. When observed from different angles, there are clear changes amidst the skull and face due to craniosynostosis (premature fusion of cranial sutures).
   • Brachycephaly: Small and broad head or clover-leaf shaped.
2. Mouth
   • Crowded, smaller, and misaligned teeth.
   • Poorly developed upper and lower jaws.

3. Eyes, nose, and ear deformities 
   • Ample distance between the eyes, eyes are often below the normal level, and strange shape of eyes.
   • Plane nasal bridge with spaced nostrils.
   • Low-leveled and deformed ears.
   • Hearing problem.
   • Vision problems.¹

4. Below the average height for their age.⁶

5. Overweight due to short-built characteristics.

6. Umbilical hernia: An abnormal bulge on the belly button.

7. At times, organs are situated differently to their anatomical position in the chest and abdomen; for example, the heart may be on the right side instead of the left side.

8. Fingers and toes
   • Syndactyly: Fusion of the fingers or toes.
   • Brachydactyly: Smaller fingers and toes than normal.
   • Polydactyly: One or more extra fingers or toes present

9. Unusual position and formation of heart: Atrial septal defect or ventral septal defect.

10. Some of the cases show mild to severe mental retardedness, while some have average intellect.

11. Inwardly aligned knees, curved upper back, malformed hips, and other skeletal defects.

12. In some cases in males, the testicles do not move in the proper place in the scrotum before birth.

Management and treatment

A multidisciplinary team coordinate together to give comprehensive care and provide appropriate treatment as per the severity of the patient's condition. Kids who have CS are observed closely. This team includes craniofacial surgeons, orthodontists, nurses, physicians, speech therapists, ophthalmologists, dental surgeons, neurosurgeons, and otolaryngologists.⁶

Early action is necessary to deal with the premature fusion of multiple cranial sutures and elevated intracranial pressure, which hinders brain development. Cranial vault reconstruction is a surgery that reshapes the skull, allowing space for proper brain development and reducing intracranial pressure. Skull malformations are best corrected from 6 months to the first year of life, ensuring the enlargement of intracranial volume, which is essential for brain development. The appearance of the individual is also improved.⁷

There are various options to manage and treat the condition depending on the patient’s condition, including:

• Heart defects: surgical intervention or medications.
• Corrective and reconstructive surgery is done for the fused fingers and toes and other skeletal deformities.
• Dental problems are ruled out with orthodontic surgery, and other essential treatment is done as per the severity of the patient. 
• Speech therapy for speech problems and rehabilitation therapy to help the patient lead an independent life, performing daily chores without help.
• Hearing aids for hearing loss.
• For vision problems, an ophthalmologist is consulted.
• Obese patients are advised to consume a healthy diet regularly to maintain a healthy weight.
• The undescended testes require surgery in male patients, which leads to infertility if left untreated.^1,7,8

Diagnosis

• Physical examination

Healthcare professionals perform a thorough physical examination to assess the clinical features of Carpenter syndrome for an accurate diagnosis.¹

• Computed tomography & Magnetic resonance imaging

To check for any anatomical deformation in the skull, heart, bones, and other parts of the body.^1,3,6

• Genetic testing

If a family has a history of CS, genetic testing of RAB23 or MEGF8 genes may be conducted to confirm the presence of Carpenter syndrome.¹ Prenatal genetic testing may be performed by taking the amniotic fluid from the placenta through chorionic villus sampling.

• Prenatal Ultrasound

Analyses the anomalous head shape, Extra fingers or toes, cardiac complications, or any organ situated in the wrong position anatomically.⁵

• Cardiac tests

Tests are done using technologies such as X-rays, echocardiography (ECG), cardiac catheterization, and Electrocardiography (EKG): To figure out any heart defects, the structure of the heart, and to find out whether the heart operates properly.^1,3

• Array Comparative genomic hybridization

To check any chromosome rearrangements in some cases.⁴

• Hearing tests

To assess any hearing loss. ⁵

Differential diagnosis of Carpenter Syndrome with similar clinical features to CS:¹

Risk factors

• Initial risk: The parents who are carriers of the mutated genes such as RAB23 or MEGF8 
• When both parents carry the mutated gene, there is a 25% chance of the kid inheriting two copies of the mutated gene in every pregnancy, causing Carpenter syndrome. Both males and females have equal chances.³ 

Complications

• People who have CS experience challenges throughout their lives, including motor skills, coordination, and cognitive development.
• Cardiac problems and other abnormal physical attributes in CS-affected children require surgical intervention.
• Physical disabilities due to CS cause difficulty in social life, and the person also faces emotional problems.⁶

FAQs

How common is carpenter syndrome?

Carpenter syndrome is an extremely rare genetic disorder with equal male and female prevalence. About 70 cases of CS are listed in the literature to date.⁴

What can I expect if I have carpenter syndrome?

It depends on the seriousness of the complications of the individual with CS. Some people may become normal with the various treatment interventions, while some require therapeutic and community assistance to cope with their problems due to the disorder.⁵ 

How can I prevent carpenter syndrome?

It cannot be prevented because Carpenter syndrome is a genetic disorder that is caused by mutations. Before conception, genetic testing may help assess the risks.¹

When should I see a doctor?

• Serious heart conditions.
• Difficulty in speech, hearing, or vision problems.
• Abnormal short and broad head of the baby.
• Dental abnormalities like underdeveloped jaws.
• Undescended testes in males.¹

Summary

Carpenter syndrome is a genetic disorder involving visible craniofacial defects, bony deformities, and sometimes heart abnormalities. CS is caused by mutations in the RAB23 gene or MEGF8 gene. CS presents with clinical features such as an abnormal conical-shaped head, wide-set eyes, extra webbed fingers or toes, underdeveloped jaws, obesity, heart deformities, etc. Diagnosis is done by physical examination, genetic testing, ultrasound, and computed tomography. People suffering from CS have to undergo certain surgeries to deal with specific challenges. Some serious patients may require professional psychological guidance and emotional assistance.