What is Pterygium Syndrome?

Pterygium syndrome, also known as multiple pterygium syndrome (MPS), is a group of rare, genetic birth disorders. These disorders have a common feature where there’s a ‘webbing’ (known as pterygia) over different parts of the body such as the neck, underarms, elbow, certain joints, and the area behind the knee. These conditions also cause multiple joints to become stiff (a condition called arthrogryposis), along with various abnormalities in the skeletal system.

There are two different types of pterygium syndrome that can be identified before a baby is born, known as ‘lethal’ and ‘nonlethal’ or ‘Escobar’ types. The lethal type is the much more serious version and can be spotted with the help of an ultrasound scan when the baby is still in the womb during the second three-month period of the pregnancy. It can cause webbing in various parts of the body, a fluid-filled swelling in the neck known as ‘hygroma colli,’ and in some instances, the baby may be stillborn. The less severe nonlethal type, Escobar syndrome, features numerous webbings, stiff joints, and distinct facial features.

What Causes Pterygium Syndrome?

Researchers have found that the cause of this syndrome is due to changes in certain genes, specifically mutations in the CHRNG gene. The CHRNG gene is responsible for producing a part of the acetylcholine receptor, a protein that plays a key role in transmitting signals between nerve cells and muscle cells. These mutations can either be the same (homogenous) or different (heterogenous) within an individual. Changes in this gene have been discovered on a specific part of chromosome 2, known as 2q37.

In addition, some families with this syndrome have shown links to another region on chromosome 2, known as 2q36 through a type of genetic testing called “genomewide linkage”.

The identified mutation affects the functioning of the acetylcholine receptor, leading to its malfunction. This messes up the communication between nerve cells and muscle cells in a developing fetus. When the signaling doesn’t work correctly, the fetus may not move as much or at all, causing pterygia – a condition where webs of skin develop – while in the womb. Moreover, this interrupted signaling contributes to several other features associated with the syndrome.

Risk Factors and Frequency for Pterygium Syndrome

Mucopolysaccharidosis (MPS) is a rare condition, and because of this, we don’t have clear data on how often it occurs or if it’s more common in certain racial groups. One thing we do know is that it affects males and females equally. There’s a 1:1 ratio of males to females who have it.

There’s evidence that suggests MPS might run in families. Many times, siblings and twins with healthy parents have been diagnosed with the condition. This suggests that MPS might be passed down through genes, with most cases seeming to follow a pattern called “autosomal recessive inheritance.” This pattern may be more common in marriages between close relatives.

That’s not the only way MPS can be passed down, though. There are also cases of it following other inheritance patterns, including ‘autosomal dominant’, ‘X-linked dominant’, ‘X-linked recessive’, and even cases where it appears randomly. However, the ‘autosomal recessive’ pattern is the one most commonly associated with MPS.

Signs and Symptoms of Pterygium Syndrome

MPS, or Multiple pterygium syndrome, presents differently based on the specific variant of the syndrome. This can make it a little difficult to pinpoint. However, many times, there have been cases in the family, presenting similar physical traits. The serious or ‘lethal’ form, presents itself during pregnancy with a cystic mass between the fetus’s head and neck, in the second trimester. This could be seen on an ultrasound and can lead to serious complications, even fetal death or stillbirth.

Some signs that expecting mothers notice might be less movement from their baby. Other symptoms can be seen on an ultrasound, such as joint issues, limited fetal movements, features of the face (like wide-set eyes, slanting eyelids, a flattened nose bridge, underdeveloped nostrils, small jaw), a cleft palate and underdeveloped lungs. Some cases even show brain anomalies and muscle atrophy.

Reduced fetal movement
Joint issues
Limited fetal movements
Abnormalities in facial features
Cleft palate
Underdeveloped lungs
Brain anomalies and muscle atrophy

The Escobar variant of MPS shows different symptoms, some which appear at birth and others that develop afterwards. Mainly, symptoms could involve extra skin on various parts of the body, joint issues, spine abnormalities, pelvic issues, hand abnormalities, and limb deformities.

Extra skin flaps in various parts of the body
Joint conditions
Spine abnormalities
Pelvic issues
Hand abnormalities
Limb deformities

Certain symptoms may appear at birth, such as low-set ears, a flat face with little or no expression, folds in the inner corner of eyes, a small mouth, a high arched palate, difficulties with sucking due to opening the mouth, underdeveloped lungs, and chest abnormalities.

Other signs can include issues with male and female genitalia, an umbilical hernia, muscle shrinkage, short stature, hearing loss, and the possibility of death. Often, walking without support begins at fifteen months, and there may be improvements or worsenings in symptoms as the child grows.

Testing for Pterygium Syndrome

Mucopolysaccharidoses (MPS) is a group of rare genetic disorders, and can be challenging to diagnose just through its symptoms, as they can mimic other conditions. However, digging into a family’s medical history can be helpful in identifying this condition, particularly if there’s a pattern of marriages within the family, as this can increase the risk of genetic disorders like MPS.

Ultrasonography during pregnancy, particularly of the lower abdomen, is used for suspected MPS cases. This type of imaging is the standard method for detecting any structural abnormalities in the developing fetus because it provides a clear view of the fluid-filled structures. Skeletal anomalies can also be identified through X-ray imaging.

In addition to these methods, if the patient’s characteristics strongly suggest MPS, genetic testing may be performed. These tests try to find changes or mutations in genes related to MPS. Testing methods include whole-exome sequencing, which examines all the protein-coding genes in a person’s DNA and Sanger sequencing, a method used to determine the exact sequence of a certain length of DNA. These tests provide confirmation on the diagnosis of MPS.

Treatment Options for Pterygium Syndrome

There’s no specific cure for Mucopolysaccharidoses (MPS), a group of metabolic disorders caused by the absence or malfunctioning of certain enzymes needed to break down molecules called glycosaminoglycans. If MPS is suspected in a child based on prenatal scans and the child is carried to term, it should be classified as a high-risk delivery. This means safety precautions and support measures should be in place at birth to steer clear of issues occurring immediately after the child is born, such as breathing difficulties arising from underdeveloped lungs or a hernia in the diaphragm.

After birth, children suspected of having MPS should be evaluated by a genetics expert and looked after by a team of health professionals addressing the multiple bodily systems affected. They cover a range of disciplines, showing just how complex and variable MPS can be.

Parents of children with MPS should consider undergoing genetic testing. This can help establish how the disorder was inherited and give an understanding of the risks of MPS occurring in future pregnancies. For patients enduring difficulties moving joints or other orthopedic issues, referrals to a surgeon for further evaluation and treatment could be beneficial. Regular check-ups are essential to monitor the child’s health and act swiftly if any MPS-related complications develop.

Research is still underway to unearth new treatment options and prevention strategies for genetic disorders like MPS, whether they are inherited or acquire later in life.

There are several genetic conditions that share some of the same symptoms as a group of diseases referred to as MPS. These similarities can sometimes make it difficult to correctly diagnose and differentiate. Some of these conditions include:

Turner syndrome: This condition is seen when an X chromosome is missing or partially missing. Common symptoms are growth problems, a webbed neck, wide-set nipples, limb swelling, short stature, learning disabilities, hypothyroidism, type 2 diabetes, kidney issues, problems of the ear, nose or throat, and heart defects. Some symptoms can overlap with those of MPS, but this syndrome does not include multiple body deformities or rigid joints.
Noonan syndrome: This genetic condition has a wide range of different symptoms including facial abnormalities, skeletal abnormalities, blood clotting problems, and heart anomalies. However, it does not include contractures (rigid joints) or issues with hearing.
Klippel-Fiel syndrome: This is a bone formation disorder that shows as abnormal bone fusion in the neck. This creates a short neck, restricted neck movements, chronic headaches, and muscle pain. It shares some features with MPS, but does not include certain physical deformities associated with MPS.
Prune belly syndrome: Also known as Eagle-Barrett syndrome, this condition includes lack of abdominal muscles, undescended testes, and urinary abnormalities. Additional features include urinary tract infections, heart defects, gut malrotation, and clubfoot. In some ways, it mimics MPS, but this condition doesn’t display a lack of abdominal muscles as seen in MPS.
Van der Woude syndrome: This type of disorder mainly affects the mouth and palate, resulting in visible defects like cleft lips and palates. This condition lacks many of the main characteristics of MPS, such as multiple physical deformities or rigid joints.
Arthrogryposis multiplex congenita: This term applies to a group of conditions that cause the joints to become stiff and contorted. It may appear by itself or with other conditions, including MPS. If it shows in isolation without the skeletal deformities or other features seen in MPS, genetic testing can rule out the possibility of MPS.

What to expect with Pterygium Syndrome

MPS is an extremely rare condition, and how serious it is depends on the severity and complexity of the symptoms present. The LMPS variant of the disease often results in babies being stillborn or dying before they’re born (known as intrauterine fetal death). If a newborn does survive pregnancy, they may have low blood pressure (hypotension), a slow heart rate (bradycardia), trouble breathing (respiratory failure), or they may die shortly after birth.

The Escobar variant of the disease has a better outlook than the LMPS variant. There have been several cases where children with this variant of the disease develop skeletal anomalies (abnormalities in the structure of the skeleton) such as kyphoscoliosis (an abnormal curvature of the spine) during childhood that required surgical evaluation and treatment. Because of a condition called amyoplasia (lack of muscle development), affected children may or may not have muscle weaknesses and may learn to move around well later in life with physical and occupational therapy, especially if they start these therapies early.

In conclusion, how well a patient with MPS does depends on the severity of the symptoms they present with and how quickly they can get treatment.

Possible Complications When Diagnosed with Pterygium Syndrome

There are several possible complications you should take into account:

Difficulty breathing and potential respiratory failure due to tight muscle contractions and fused ribs that restrict the functioning of the lungs
Underdevelopment of the lungs leading to respiratory distress at birth
Hearing problems often associated with a type of hearing loss that’s caused by blockage or damage in the outer and/or middle ear
Delay in speech development
Loss of mobility due to limitations in joint movements
Poor eating habits and malnutrition because of feeding difficulties or due to a split in the roof of the mouth during the first days of life
Heart failure due to underdeveloped heart structures
Potential death before birth

Preventing Pterygium Syndrome

For those caring for patients with multiple pterygium syndrome, it’s crucial to understand that this condition is permanent and will require continued outpatient check-ups. Outpatient check-ups refer to meetings with a doctor or health care provider that do not require an overnight stay in a hospital. In addition to this, there may be related problems that families should be prepared for. This may result in the need for extra visits with different doctors or specialists further down the line.

Providing the right advice and information to patients and their families is a critical part of treating children with this condition. By keeping everyone fully informed, we’re able to ensure the best possible care for these children.