What is Char Syndrome?
Char syndrome is a rare genetic disorder that’s usually passed down through families. This condition is characterized by three main features; uncommon facial characteristics, a heart defect called patent ductus arteriosus (PDA), and underdevelopment of the middle bone of the little fingers. The syndrome was first identified by Florence Char in 1978 when she noticed these characteristics in a child.
People with Char syndrome often have certain facial features such as a flattened nose, eyes that are far apart, eyelids that tilt downwards, slight drooping of the eyelids, a shorter area between the nose and upper lip with prominent lines, an upward slanting lip line giving a triangular mouth appearance, and unusually thick and outward rolling lips. The most common heart problem seen in these individuals is PDA.
Few people with Char syndrome may also have other heart defects, abnormalities in hands and feet, missing teeth, hearing loss, short-sightedness or eyes that do not align properly, extra nipples, sleep disorders, unusual head shape due to premature closure of the skull sutures, and short height.
What Causes Char Syndrome?
The exact cause of Char syndrome isn’t fully understood yet. However, recent research hints that it might be caused by changes in a gene called transcription factor AP-2 Beta (TFAP2B). This condition is passed down through families in a way that only requires one copy of the changed gene to cause the condition. This is known as an autosomal dominant inheritance.
In this context, Char syndrome has complete penetrance but variable expressivity. This means that the changed gene will always cause the disorder, but the degree of symptoms can vary from person to person.
One commonly seen change in the TFAP2B gene is known as a missense mutation. This error changes one part of the gene’s instruction set, which is crucial for binding with DNA. Other reported changes include point mutations within introns (non-coding sections of the gene) and changes known as frameshift deletions, which interfere with how the rest of the gene is read and interpreted.
Risk Factors and Frequency for Char Syndrome
Char syndrome is a very rare condition with only a handful of cases reported globally. Its exact prevalence is hard to measure because of its scarcity and the chance it may be under-diagnosed. But, according to current information, it is estimated to occur in about 1 in every 100,000 to 200,000 births. Char syndrome does not favor any gender, affecting both males and females evenly. Furthermore, it has been observed in different ethnic groups.
Signs and Symptoms of Char Syndrome
Char syndrome is a genetic condition that varies greatly in how it affects patients, therefore, diagnosis and treatment need to be personalized.
Most patients with Char syndrome, more than 80%, display peculiar facial features such as flattened cheekbones, a flat nasal bridge, a wide and prominent nose, a short upper lip area with noticeable ridges, slightly drooping eyelids, eyes that slope downward and are spaced far apart, and a distinct mouth shape with thick, outward-turning lips.
Heart defects are another usual symptom, with the most common one, found in 68% of patients, being PDA or patent ductus arteriosus. PDA is a connection between the lung artery and the aorta (main artery) that usually closes after birth. But in Char syndrome patients, it may stay open, causing a disruption in normal blood flow. This can lead to increased blood flow to the lungs and potentially create a condition called pulmonary hypertension if not addressed. Infants with PDA may show signs like rapid breathing, trouble eating, and poor growth. If PDA is not treated, it can lead to severe heart problems.
Hand abnormalities are also associated with Char syndrome, being seen in 57% of cases. These can manifest as the pinky finger bending inwards towards the ring finger, the middle bone of the fifth finger being under-developed or completely absent, fingers being fused together, or short fingers.
Less frequently, symptoms like nearsightedness, cross-eyedness, hearing issues, skeletal irregularities, premature fusion of certain skull bones, missing second or third molars, short height, and intellectual disability may also be seen in individuals with Char syndrome.
Testing for Char Syndrome
If there’s a chance someone might have Char syndrome, doctors usually use a mix of clinical check-ups, imaging tests, and genetic testing to figure out if they have it. The doctors will look into the patient’s medical history in detail and conduct a full physical examination focusing on any birth defects affecting the eyes, ears, heart, and teeth.
Imaging tests like computed tomography (CT) scans or magnetic resonance imaging (MRI) are used to get a closer look at the abnormalities in the eyes, ears, and any other organs that might be affected. Echocardiography, a test that shows the structure and function of the heart, is used to detect PDA (Patent Ductus Arteriosus: a persistent opening between two major blood vessels leading from the heart) and other heart anomalies linked to the condition.
Genetic testing is crucial in the diagnosis process of Char syndrome as it can confirm the presence of the disorder, identify the mutation causing it, and aid in genetic counselling. These tests can pinpoint mutations in specific genes. There are different types of genetic tests, like gene-targeted sequencing and whole-exome sequencing. If someone shows symptoms that suggest Char syndrome, gene-targeted tests like single gene testing and multi-gene panels are used. On the other hand, if Char syndrome isn’t initially suspected, doctors might use whole-exome sequencing or gene panel testing. Choosing the best test needs a careful review of the patient’s symptoms, potential diagnoses, and the resources available.
Treatment Options for Char Syndrome
Char syndrome is a condition that requires careful and cooperative management across several medical specialties. This means that professionals like pediatricians, geneticists, facial surgeons, heart doctors, eye specialists, ear, nose, and throat doctors, and surgeons who specialize in bone problems may all need to work together on a patient’s treatment plan.
The treatments themselves can be quite varied and can include surgery to correct birth defects of the heart, managing any abnormalities in the eyes and ears, and repairing any blockages in the nasal passage. In some cases, heart surgery may be needed to correct abnormal blood flow, specifically regarding an issue called PDA. This essentially involves a vessel in the heart that didn’t close up like it should have after birth. Surgeons can either tie off this vessel or use a device to close it during a procedure using a small tube (catheter).
Sometimes, surgery to correct facial features associated with Char syndrome is also considered. This might make the face appear more typical and could also improve function in certain areas. However, these surgeries are complex and should be thought through carefully.
It is also necessary to monitor people with Char syndrome regularly. This often includes yearly checks for vision and hearing, dental check-ups every six months, regular assessments for sleep disorders, and watching the growth of the head regularly during infancy.
Early diagnosis and treatment can really help improve the life quality of patients with Char syndrome. It can also contribute to their development.
Another essential part of managing Char syndrome is genetic counselling. This is a process where families get information about how Char syndrome is inherited and the chances of having children with the condition in the future. Char syndrome is usually passed from parent to child. So, if a parent has Char syndrome, there’s a 50% chance they will pass the condition on to their child. Still, it can also happen randomly in people with no family history of the syndrome. These are called “de novo” mutations. If doctors need to check for Char syndrome before a baby is born, they can do this through two procedures called chorionic villus sampling, or CVS, or an amniocentesis, which both involve testing fluid or tissue from the womb for the gene mutation associated with Char syndrome.
What else can Char Syndrome be?
When a doctor is trying to diagnose Char syndrome, they need to keep in mind that it can easily be confused with other genetic disorders. This is because Char syndrome presents with similar characteristics like facial abnormalities, heart defects at birth, and issues with limb development. These overlapping features make it necessary to carry out thorough genetic and clinical tests to clearly identify Char syndrome and not mistake it for another condition. Char syndrome could be confused with the following disorders:
- 22q11.2 deletion syndrome (also known as Di George syndrome)
- Holt-Oram syndrome
- Treacher Collins syndrome
- Cri-du-chat syndrome
- Rubinstein-Taybi syndrome
- Ellis-van Creveld syndrome
As such, careful consideration and comprehensive assessment are important in accurately diagnifying Char syndrome.
What to expect with Char Syndrome
The outlook for people with Char syndrome can greatly differ based on how severe their heart defects are and if they have any additional health issues. If heart abnormalities are detected and managed early, this can greatly improve the person’s life quality and health outlook. However, some people might face long-term complications such as learning disabilities, vision problems, and heart failure.
Possible Complications When Diagnosed with Char Syndrome
Char syndrome can lead to several complications, potentially affecting quality of life and overall health. Individuals with this condition may face a range of complications that could include difficulty breathing due to choanal atresia, problems with feeding, hearing loss, developmental disabilities, and problems with bone formation.
Heart defects, especially patent ductus arteriosus (PDA), can turn into heart failure and other heart-related problems if not treated properly. Abnormalities in the face and limbs might cause problems with functioning and might need surgical correction. Plus, the emotional impact of visible physical abnormalities can influence personal confidence and social interactions.
Complications of Char syndrome:
- Breathing difficulties due to choanal atresia
- Feeding difficulties
- Hearing loss
- Developmental disabilities
- Skeletal abnormalities
- Heart issues, especially due to patent ductus arteriosus (PDA)
- Functional impairment due to facial and limb abnormalities
- Negative self-esteem and social interactions due to visible physical anomalies
Preventing Char Syndrome
Char syndrome is a rare condition, so there aren’t many ways to prevent it. But if it runs in your family, genetic counseling and prenatal testing become very important. Tests like CVS (Chorionic Villus Sampling) or amniocentesis can help identify family members who may carry the gene and find if the condition is present in an unborn baby.
One of the best things people affected by Char syndrome can do is to learn more about the condition. Understanding how it’s passed down, how it affects people differently, and what to expect in the future can be very empowering. It’s also important to know about current treatment options, what advancements might be on the horizon, and the importance of regular check-ups and managing medication. Preventing complications and getting support from others going through the same thing can make a big difference in patients’ lives and gives them a more active role in their care, helping to improve their overall quality of life.
