Related Terms

• Bowen-Armstrong syndrome, cleft lip/palate-ectodermal dysplasia syndrome, CLPED1, consanguinity, ectodermal dysplasia, ectodermal dysplasia cleft lip and palate mental retardation and syndactyly, Margarita Island ectodermal dysplasia, PVRL1, Rosselli-Gulienetti syndrome, Zlotogora-Ogur syndrome.

Background

• Rosselli-Gulienetti syndrome (RGS) 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.

• Symptoms of RGS include reduced or absent ability to sweat, facial abnormalities, and defects in the hair, teeth, nails, fingers, toes, and urinary tract. Specifically, symptoms of RGS include cleft lip or palate, intellectual disability, fused eyelids, absent nails, delayed bone growth, urogenital abnormalities, and dry skin. This is a congenital disorder and is present at birth.

• RGS is an inherited genetic disease, which means that is passed down among family members. There are reports that it is caused by a mutation or defect in the PVRL1 gene, which provides instructions for making the protein nectin-1. Nectin-1 is an immunoglobulin-like adhesion molecule that is widely expressed in epithelial tissues, and it participates in forming the adherens junctions, which serve to connect cells within the skin.

• RGS follows an autosomal recessive pattern of inheritance, meaning that two copies of the defective gene, one from the mother and one from the father, must be inherited for the disease to appear.

• RGS is extremely rare, and its exact incidence is unknown. It was first described by the researchers Rosselli and Gulienetti in 1961. There were nine known cases as of 1988. Males and females are affected in equal numbers. Its incidence tends to be higher in children of parents who are consanguineous (closely related or sharing genetic material).

• The long-term prognosis for people with RGS is largely unknown because there are so few cases. If symptoms are managed and complications prevented, people with RGS should enjoy long, healthy lives.

Risk Factors

• Because Rosselli-Gulienetti syndrome (RGS) is inherited, the only known risk factor is a family history of the disease. RGS may be caused by a mutation or defect in the PVRL1 gene. RGS is usually 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 condition to appear.

Causes

• General: Rosselli-Gulienetti syndrome (RGS) is a rare inherited genetic disorder that is passed down among family members in an autosomal recessive pattern. It is caused by a mutation or defect in the PVRL1 gene. This gene provides the instructions for making the protein nectin-1. Nectin-1 is an immunoglobulin-like adhesion molecule that is widely expressed in epithelial tissues and participates in forming the adherens junctions, which serve to connect cells within the skin.

• Autosomal recessive: RGS follows an autosomal recessive pattern of inheritance, meaning that an individual must inherit two copies of the defective gene, one from each parent. Individuals who inherit only one copy of the defective PVRL1 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, then each child will have a 50% chance of inheriting one defective gene and 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 RGS.

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

Signs and Symptoms

• Cognitive: People with Rosselli-Gulienetti syndrome (RGS) often have intellectual disabilities.

• Face: People with RGS tend to have a cleft palate (an incomplete closure of the roof of the mouth), a cleft lip (an abnormal groove in the upper lip beneath the nose), or both. The face may be narrow and have distinctive features, including a wide, flat nose and a chin that sticks out. In addition, the ears may be large and low-set. The eyelids may be fused.

• Hair: People with RGS have sparse or no hair on the scalp. Hair that is present is often brittle and coarse and may appear twisted. Eyebrows and eyelashes may also be sparse.

• Hands and feet: The fingers and toes may be deformed. In some cases, they are fused together.

• Nails: The nails tend to be poorly developed.

• Skin: People with RGS lack the ability to sweat, a condition also known as anhidrosis. The palms of the hands and soles of the feet also tend to be covered with thick, dry skin.

• Teeth: The teeth tend to be poorly developed, abnormally small, or absent. People with RGS are especially prone to cavities.

• Other: People with RGS tend to be of normal stature, although bone growth may be delayed. They may have extra nipples and growths on the backs of the knees and near the anus. There have been reports of people with RGS and spina bifida, the incomplete closure of the skin at the base of the spine.

Diagnosis

• General: Rosselli-Gulienetti syndrome (RGS) may be suspected based on distinctive characteristics of the hair, face, teeth, skin, hands, and feet. Specifically, symptoms of RGS include cleft lip or palate, intellectual disability, fused eyelids, absent nails, delayed bone growth, urogenital abnormalities, and dry skin. This is a congenital disorder and is present at birth. Nevertheless, a thorough family history and complete physical exam should be completed. Diagnosis can often be made at birth.

• Genetic testing: If RGS is suspected, deoxyribonucleic acid (DNA) sequencing can be done from a blood sample to determine whether the individual carries a defective PVRL1 gene. If this defective gene is detected, a positive diagnosis is made.

• Imaging: Imaging studies such as X-ray may allow clinicians to observe the characteristic delayed bone growth in the hands and feet seen in RGS. Ultrasound may also detect the presence of a cleft palate (an incomplete closure of the roof of the mouth) in a developing fetus.

• Prenatal DNA testing: If there is a family history of RGS, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose RGS. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional.

• During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.

• During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutation in the PVRL1 gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Complications

• Recurrent infections: The presence of a cleft palate (incomplete closure of the roof of the mouth) may predispose people with RGS to develop recurrent ear infections, also known as otitis media.

• Speech and language problems: The presence of a cleft lip or palate may lead to speech and language problems.

• Urinary system problems: People with RGS may have problems with the urinary system, such as an abnormal urinary opening.

Treatment

• General: There is no cure for Rosselli-Gulienetti syndrome (RGS). Treatment aims to reduce symptoms and prevent complications. People with RGS should be regularly seen by a geneticist, urologist, dermatologist, and various surgeons, depending on individual patient needs. In addition, people with RGS should be advised to maintain proper hydration and avoid overly strenuous activities that could lead to hyperthermia.

• Dental care: People with RGS should practice good preventive dental care, including brushing their teeth at least twice daily and flossing once daily, seeing the dentist every six months, and avoiding cavity-causing foods and beverages. In addition, crowns or composite fillings may be used on small teeth. Partial or full dentures, implants, or dental surgery may be needed for missing teeth.

• Education: By law, patients with RGS syndrome who suffer from 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 RGS 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.

• Speech-language therapy: Some patients with RGS may benefit from speech-language therapy because of the presence of a cleft lip or palate. 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.

• Surgery: Surgery may repair a cleft palate (an incomplete closure of the roof of the mouth) as well as separate fused fingers and toes.

Integrative Therapies

• Currently there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of Rosselli-Gulienetti syndrome (RGS).

Prevention

• General: Because Rosselli-Gulienetti syndrome (RGS) is an inherited condition, there is currently no known way to prevent the disease. However, a number of options are available for prospective parents with a family history of RGS.

• Genetic testing and counseling: Individuals who have RGS may meet with a genetic counselor to discuss the risks of having children with the disease. Individuals with a family history of RGS may meet with a genetic counselor to determine whether they carry the defective PVRL1 gene. Carriers can be determined through detailed family histories or genetic testing.

• Known carriers of RGS may undergo genetic counseling before they conceive a child. Genetic counselors can explain the options and the associated risks of various tests, including preimplantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).

• Preimplantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective PVRL1 gene, and only the embryos that are not affected may be selected for implantation. Because RGS can be detected in a fetus, parents may choose whether to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.

Author Information

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

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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