Gorlin-Chaudhry-Moss syndrome

BACKGROUND

Gorlin-Chaudhry-Moss (GCM) syndrome is a form of ectodermal dysplasia, one of a group of syndromes deriving from abnormalities of the ectodermal structures, which include the hair, teeth, nails, sweat glands, cranial-facial structure, and hands. These are genetic disorders that can be inherited in an autosomal dominant or recessive manner.

GCM is characterized by premature closure of the fibrous joints, or sutures, between certain bones in the skull (craniosynostosis), unusually small eyes (microphthalmia), absence of some teeth (hypodontia), and excessive amounts of hair (hypertrichosis) on most areas of the body. Affected individuals may also exhibit a mild delay in physical development (growth retardation); short fingers and toes; and underdevelopment (hypoplasia) of the two long folds of skin on either side of the vaginal opening (labia majora) in females. In addition, there may be an abnormal opening between the two large blood vessels that carry blood away from the heart, also known as the pulmonary artery and aorta, which can cause patent ductus arteriosus, an inappropriate recirculation of some blood through the lungs, rather than throughout the rest of the body. Some people with GCM may have delayed growth and hearing loss. Some may have mild intellectual disabilities, while others may be of normal intelligence.

GCM syndrome is inherited or passed down among family members. Although the genetic mutation or defect that causes GCM is unknown, the disorder is believed to be inherited as an autosomal recessive trait, meaning that two copies of the defective gene, one from each parent, must be inherited for the disease to appear.

GCM is extremely rare with about four known cases documented in the scientific literature. Incidence of the disorder is unknown. The disorder was first described by Gorlin in 1960 in two sisters, who were followed up by another researcher in 1992 at the ages of 34 and 36 years old.

RISK FACTORS

Currently, the only known risk factor for Gorlin-Chaudhry-Moss (GCM) syndrome is a family history of the disease. GCM is believed to be inherited, or passed down among family members, as a recessive trait, meaning that two copies of the defective gene, one from each parent, must be inherited for the disease to appear. The exact genetic mutation that causes GCM is still unknown.

CAUSES

Gorlin-Chaudhry-Moss (GCM) syndrome is an inherited genetic disease passed down among family members. However, the exact genetic mutation or defect that causes GCM is still unknown.

Autosomal recessive inheritance: GCM is inherited as an autosomal recessive trait, meaning that an individual must inherit two copies of the defective gene, one from each parent, for the disease to appear. Individuals who inherit only one copy of the defective gene generally have no symptoms and are called carriers because they can pass on the disorder to their children.

If one parent is a carrier, or has one only copy of the defective gene, then each child has a 50% chance of inheriting one defective gene and of also being a carrier. If both parents are carriers, each child has a 25% chance of inheriting two defective genes, a 50% chance of inheriting only one defective gene, and a 25% chance of inheriting neither defective gene. Therefore, if both parents are carriers, about one out of four children will have the disorder.

Random occurrence: It is currently unknown whether GCM can occur as the result of a spontaneous genetic mutation with no family history of the disease.

SIGNS AND SYMPTOMS

General: As in most ectodermal dysplasias, the eyes, hair, and teeth are affected in patients with Gorlin-Chaudhry-Moss (GCM) syndrome. Symptoms are generally present at birth.

Dental: People with GCM often have dental problems such as absent teeth.

Eyes: People with GCM often have many problems with the eyes. These include abnormally small and widely spaced eyes, an inability to open or close the eyes completely, small gaps or holes in the upper eyelids (colobomas), and wrinkles in the skin of the upper eyelids (oblique palpebral fissures). In addition, people with GCM may have involuntary movements of the eyes when they look sideways, a limited ability to look upward, and scars on the corneas. Vision problems may be caused by astigmatism and farsightedness.

Hair: People with GCM tend to develop excessive amounts of hair on most parts of the body. They also tend to have a low hairline.

Head: People with GCM tend to have a wide head and an underdeveloped nose and upper jawbone. Some of the other bone structures in the skull develop abnormally in some individuals with GCM.

Hearing: People with GCM tend to have conductive hearing loss.

Heart: People with GCM have been known to develop a heart problem called patent ductus arteriosus, which is characterized by a hole or connection in the two large blood vessels that carry blood away from the heart. This causes some of the blood to recirculate through the lungs rather than going to other parts of the body. If the defect is small, it may close on its own. If it is large enough and does not close on its own by age two, it may need to be surgically repaired.

Other: Females with GCM may have underdeveloped labia majora, or the outermost part of the genitalia. In addition, many people with GCM have an abdominal hernia. People with GCM may also have short fingers and toes and delays in physical growth, which leads to short stature.

DIAGNOSIS

General: Gorlin-Chaudhry-Moss (GCM) syndrome may be suspected based on the observation of the condition's distinctive features of the head, face, hair, and eyes. Specifically, GCM is characterized by premature closure of the fibrous joints (sutures) between certain bones in the skull (craniosynostosis), unusually small eyes (microphthalmia), absence of some teeth (hypodontia), and excessive amounts of hair (hypertrichosis) on most areas of the body. Affected individuals may also exhibit a mild delay in physical development (growth retardation), short fingers and toes, and underdevelopment (hypoplasia) of the two long folds of skin on either side of the vaginal opening (labia majora) in females. In addition, there may be an abnormal opening between the two large blood vessels that carry blood away from the heart, also known as the pulmonary artery and aorta, which can cause patent ductus arteriosus, an inappropriate recirculation of some blood through the lungs, rather than throughout the rest of the body. In addition, a detailed family history and complete physical exam should be completed.

Dental exam: A dental exam can be used to assess the condition of the teeth, important because individuals with GCM are prone to tooth loss.

Eye exam: Individuals with GCM not only have physical abnormalities of the eye and surrounding area, they may also have involuntary movements of the eyes when they look sideways, a limited ability to look upward, and scars on the corneas. Vision problems may be caused by astigmatism and farsightedness.

Hearing tests: Individuals with GCM have been reported to have conductive hearing loss, so a hearing test may be used to determine the extent of any hearing loss.

Imaging: Imaging studies such as X-rays may be done to assess the bones of the fingers, toes, and skull to determine the degree to which the bones in the skull are formed.

An echocardiogram (ECG) may be done to assess the health of the heart and to diagnose the presence of patent ductus arteriosus. An ECG is a painless and noninvasive procedure during which sound waves are used to create a moving picture of the heart. Reflected sound waves allow the clinician to observe the heart's structure and function.

COMPLICATIONS

Heart: People with Gorlin-Chaudhry-Moss (GCM) syndrome tend to develop a heart problem called patent ductus arteriosus. This condition is characterized by a hole in the two large blood vessels that carry blood away from the heart. This causes some of the blood to recirculate through the lungs rather than going to other parts of the body. If the defect is small, it may close on its own. If it is large enough and does not close on its own by age two, it may need to be surgically repaired.

Vision problems: People with GCM may have impaired vision from astigmatism and farsightedness.

TREATMENT

There is currently no known cure for Gorlin-Chaudhry-Moss (GCM) syndrome. Instead, treatment aims to reduce symptoms and prevent complications.

Education: By law, patients with GCM syndrome who have intellectual disabilities must have access to education that is tailored to their specific strengths and weaknesses. According to the Individuals with Disabilities Education Act, all children with disabilities must receive free and appropriate education. This law states that staff members of the patient's school must consult with the patient's parents or caregivers to design and write an individualized education plan based on the child's needs. The school faculty must document the child's progress in order to ensure that the child's needs are being met.

Educational programs vary among patients depending on the child's specific learning disabilities. In general, most experts believe that children with disabilities should be educated alongside their nondisabled peers. The idea is that nondisabled students will help the patient learn appropriate behavioral, social, and language skills. Therefore, some GCM patients are educated in mainstream classrooms. Others attend public schools but take special education classes. Still others attend specialized schools that are equipped to teach children with disabilities.

Corrective lenses: Individuals with GCM who have vision problems may benefit from corrective lenses or glasses. Glasses can correct both astigmatism and farsightedness.

Dental care: Patients with GCM should practice good preventive dental care, including regular flossing, teeth brushing, and visits to the dentist. Dentures may be appropriate for patients with GCM who are missing teeth.

Hearing aids: GCM patients who experience hearing loss may benefit from hearing aids. These battery-operated devices are available in three basic styles: behind-the-ear, in-the-ear, and inside the ear canal. Patients should talk to a healthcare provider to determine the type of hearing aid that is best for them. A behind-the-ear device is used for mild to profound hearing loss. The device is worn behind the ear and is attached to a plastic ear mold inside the outer ear. In-the-ear hearing aids are worn inside the outer ear, and are used for mild to severe hearing loss. Canal hearing aids are smaller hearing aids that fit inside the patient's ear canal. These are used for mild to moderately severe hearing loss.

If hearing loss is severe, patients may benefit from cochlear implants. These electronic devices are surgically implanted inside the ears. Unlike a hearing aid, which amplifies sound, a cochlear implant makes up for damaged parts of the inner ear.

Speech language therapy: Some patients with GCM may benefit from speech-language therapy because these individuals often develop communication skills more slowly than normal. During speech-language therapy, a qualified speech-language professional (SLP) works with the patient on a one-to-one basis, in a small group, or in a classroom to help the patient improve speech, language, and communication skills. Programs are tailored to the patient's individual needs.

Speech pathologists use a variety of exercises to improve the patient's communication skills. Exercises typically start simple and become more complex as therapy continues. For instance, the therapist may ask the patient to name objects, tell stories, or explain the purpose of an object.

On average, patients receive five or more hours of therapy per week for three months to several years. Doctors typically recommend that treatment be started early to ensure the best possible outcome for the child.

Drugs: Patent ductus arteriosis, characterized by the connection between the two large blood vessels that carry blood away from the heart, that causes blood to recirculate to the lungs, may be treated with drugs. Indomethacin, a prostaglandin, or ibuprofen, both nonsteroidal anti-inflammatory drugs (NSAIDs), may help close the hole by stimulating it to tighten. Although these drugs differ chemically, the most common side effects are nausea, vomiting, diarrhea, constipation, decreased appetite, rash, dizziness, headache, and drowsiness. NSAIDs may also cause fluid retention, leading to edema. This treatment generally works in premature infants but not in full-term infants.

Catheters: A catheter is a tube that can be inserted into a body cavity, duct, or vessel to allow drainage of excess bodily fluids. A catheter-based procedure may be used in infants and children who are slightly older. Catheters generally cannot be used in preterm infants. In this procedure, called a transcatheter device closure, a small tube is inserted into a large blood vessel in the upper thigh and is guided toward the heart. A device is inserted into the tube to block the hole in the heart that causes patent ductus arteriosis. Patients are sedated during this procedure, and recovery is generally quick. The procedure is often done on an outpatient basis and the patient may return home the same day. Complications associated with this procedure are rare and minor, including bleeding, infection, and movement of the blocking device from its intended location.

Surgery: Surgery may be required if patent ductus arteriosus causes additional health problems, if the child is too young for a catheterization, or if the catheterization procedure fails to repair the problem. Surgery is often delayed until six months of age.

During surgery, a small cut is made between the ribs of the patient to reach the hole in the heart. Then the hole is closed with stitches or clips. Complications from this procedure are generally rare, and include hoarseness, paralysis of the diaphragm (the muscle used to breathe), infection, bleeding, or collection of fluid in the lungs.

Because the procedure is more invasive than the catheter-based procedure, it is done in the hospital and the patient is required to stay for about two days. Education is provided to the patient and caregivers so they can properly care for the wound and be aware of signs of complications.

INTEGRATIVE THERAPIES

Currently there is a lack of available scientific evidence on the use of integrative therapies for the treatment or prevention of Gorlin-Chaudhry-Moss (GCM) syndrome. The therapies listed below have been studied for hearing loss, should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies or preventive measures.

Unclear or conflicting scientific evidence:

Acupuncture: Preliminary evidence suggests that there is likely no benefit from acupuncture in hearing loss in adults or children. However, this evidence is from small studies, and more research is needed before a definitive conclusion can be reached.

Acupuncture is likely safe when performed by an experienced practitioner using the standard sterile technique. Very few serious complications have been documented, despite millions of treatments conducted every year. Observational studies and randomized trials reviewing thousands of treatments have not noted any grave adverse reactions. Rare serious and potentially lethal complications have been noted in case reports, including infection and organ, nerve, or vascular injury. There are several reports of fatalities in the available medical literature. Acupuncture may be unsafe in patients with emphysema or other pulmonary disease, based on multiple case reports of pneumothorax, or tears in the lung. Special care should be taken with pregnant women to protect the fetus and prevent stimulation of contractions. Acupuncture may be unsafe when used in individuals with bleeding disorders, unstable medical conditions, or infections. Despite theoretical concerns for bleeding disorders, case reports have not documented adverse effects of acupuncture related to uncontrolled bleeding. Use caution when electrostimulation acupuncture is used in pregnant women, in patients with cardiac disorders, including those with a pacemaker, because of the risk of arrhythmia or interference with pacemaker functioning.

Noni: Noni juice has been used for many years for a wide variety of indications in Southeast Asia. Noni juice has shown some evidence of beneficial effects in improving hearing in people with auditory dysfunction, but more study is needed.

Overall, noni has had very few reported side effects. Although noni roots are known to contain liver damaging constituents, there is controversy about whether use of noni would actually damage the liver.

PREVENTION

General: Because Gorlin-Chaudhry-Moss (GCM) syndrome is an inherited condition, there is currently no known way to prevent the disease.

Genetic testing and counseling: Individuals who have GCM may meet with a genetic counselor to discuss the risks of having children with the disease. Individuals with a family history of GCM may meet with a genetic counselor to discuss the possibility of passing on the disease to their children. Because the genetic mutation that causes GCM is currently unknown, genetic tests that can diagnose GCM are currently unavailable.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

• Feinberg SB. Congenital mesodermal dysmorpho-dystrophy (brachymorphic type). Radiology. 1960;74:218-24. View abstract
• Gorlin RJ, Chaudhry AP, Moss ML. Craniofacial dysostosis, patent ductus arteriosus, hypertrichosis, hypoplasia of labia majora, dental and eye anomalies-a new syndrome? J Pediatr. 1960;56:778-85. View abstract
• Ippel PF, Gorlin RJ, Lenz W, et al. Craniofacial dysostosis, hypertrichosis, genital hypoplasia, ocular, dental, and digital defects: confirmation of the Gorlin-Chaudhry-Moss syndrome. Am J Med Genet. 1992;44:518-22. View abstract
• National Foundation for Ectodermal Dysplasias. www.nfed.org. Accessed April 15, 2008.
• Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2009.
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