Orofaciodigital syndrome type I

• Orofaciodigital syndrome type I (OFD I) is a form of ectodermal dysplasia, a group of disorders that affect the outer layer of the developing embryo. This layer, called the embryonic ectoderm, develops into many parts of a baby's body, including the eyes, skin, nails, and hair. In ectodermal dysplasias, these parts do not develop normally.
• As implied by the name of the condition, OFD I affects the mouth, face, fingers, and toes. Specifically, symptoms of OFD I may include a cleft palate, an incomplete closure of the roof of the mouth, or a cleft lip, an abnormal groove in the upper lip beneath the nose. Patients also tend to have poorly developed or absent teeth.
• OFD I also affects the kidneys as well as the central nervous system, which consists of the brain and spinal cord. Some people with OFD I also have intellectual disabilities.
• OFD I is caused by a mutation or defect in the OFD1 gene, located on the X chromosome. Most cases of OFD I are caused by a spontaneous mutation or defect in the egg or sperm cell or in the developing embryo. Fewer cases of OFD I are inherited, or passed down, among family members. When inherited, OFD I appears to follow an X-linked dominant pattern of inheritance. Most cases of OFD I occur in females because males with the defective OFD1 gene do not generally survive past birth.
• OFD I is rare. However, it is the most common of the 11 orofaciodigital syndromes. Worldwide incidence of OFD I is estimated to be between one in 50,000 to one in 250,000 live births. It appears to affect all races and ethnicities in equal numbers. However, OFD I affects more females than males.

• Because orofaciodigital syndrome type I (OFD I) can be inherited, the only known risk factor is a family history of the disease. Incidence of OFD I is estimated to be between one in 50,000 to one in 250,000 live births. It appears to affect all races and ethnicities in equal numbers. However, OFD1 affects more females than males.

• Genetic mutations: Orofaciodigital syndrome type I (OFD I) is caused by a mutation or defect in the OFD1 gene. This gene provides instructions for making the OFD1 protein. This protein is likely involved with normal kidney function, but it is currently poorly understood.
• Random occurrence: About 75% of OFD I cases occur in individuals with no family history of the disease. These cases occur as the result of a spontaneous genetic mutation or defect in the egg or sperm cells or in the developing embryo.
• X-linked dominant inheritance: The remaining cases of OFD I are inherited as X-linked dominant traits. Females have two copies of the X chromosome, but males have one X chromosome and one Y chromosome. Males inherit an X chromosome from the mother and a Y chromosome from the father, so a male can inherit the OFD1 gene only from the mother. Most cases of OFD I are seen in females because it is believed that males with the defective OFD1 gene do not survive past birth. Males who do survive past birth may have two X chromosomes and one Y chromosome (XXY).

• General: Many signs and symptoms of orofaciodigital syndrome type I (OFD I) are usually present at birth. People with milder forms of the disease may not show symptoms until later in life. As in most ectodermal dysplasias, OFD I affects the hair, teeth, and nails. In addition, severity of OFD I symptoms vary widely.
• Face: Facial characteristics of OFD I may include small nostrils, a cleft palate (incomplete closure of the roof of the mouth during development), or a cleft lip (abnormal groove in the upper lip beneath the nose).
• Hair: People with OFD I may lose their hair (alopecia) at an early age or have bald patches.
• Hands: Patients with OFD I may have fingers that are fused, curved (particularly the little finger), or abnormally short. There may also be extra fingers.
• Kidney: About 15-50% of OFD I patients also develop a kidney condition known as polycystic kidney disease. In polycystic kidney disease, small fluid-filled sacs called cysts form on the kidneys. These cysts replace most of the normal kidney tissue and cause the kidney to become enlarged, leading to loss of kidney function. Patients with OFD I may also develop cysts in other areas of the body, especially the pancreas and brain.
• Nervous system: In up to 40% of cases, OFD I affects the central nervous system, which consists of the brain and spinal cord. Porencephaly is emerging as a common central nervous system condition in patients with OFD I. In this condition, a cyst, or fluid-filled cavity, develops in the brain. Symptoms of porencephaly may include seizures, partial paralysis, and abnormally small or large head size.
• Teeth and mouth: Patients with OFD I may have poorly developed or absent teeth, particularly the incisors and canines. The tongue may be split or appear to be divided into lobules.
• Other: Some patients with OFD I have intellectual disabilities. Rare cases of brain malformations have been reported in cases of severe OFD I.

• General: Symptoms of orofaciodigital syndrome type I (OFD I) range from mild to severe. OFD I is usually diagnosed early in life but, in the case of very mild symptoms, it may not be diagnosed until later in life. OFD I may be suspected based on the distinctive features of the face, hands, and teeth. In addition, a detailed family history and complete physical exam should be completed.
• Imaging: X-rays may allow a clinician to observe abnormalities of the bones of the hands and fingers.
• Ultrasound: An ultrasound of the kidneys is a safe, noninvasive imaging method that uses sound waves to take pictures of the kidneys. This is the most common imaging method used to check for cysts in patients.
• Genetic testing: If OFD I is suspected, a DNA test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the defect in the OFD1 gene. If this is detected, a positive diagnosis is made.
• Prenatal DNA testing: If there is a family history of OFD I, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose OFD I. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional. Testing for rare diseases, including OFD I, is often limited and may not be available in the United States.
• During amniocentesis, a long, thin needle is inserted through the abdominal wall 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 OFD1 gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

• Ear infections: Patients with orofaciodigital syndrome type I (OFD I) may have cleft lips or palates. Babies with cleft palates have an increased risk of developing frequent ear infections that may eventually lead to permanent hearing loss.
• Feeding difficulties: A cleft lip or palate typically causes difficulty with feeding. This is because suction may not be possible, making it difficult to obtain milk from the mother's breast or bottles.
• Kidney: About 15-50% of OFD I patients develop a kidney condition known as polycystic kidney disease. If left untreated, polycystic kidney disease may progress to kidney failure.
• Limited mobility: Defects in the hands may limit mobility and the development of fine motor skills.
• Speech and language problems: If the facial malformations associated with OFD I are not surgically corrected, they may lead to speech and language problems. Sounds cannot be properly made with certain facial malformations.

• General: There is currently no known cure for orofaciodigital syndrome type I (OFD I). Instead, treatment aims to reduce symptoms and prevent complications.
• Dialysis: When the kidneys begin to fail, patients can undergo dialysis to restore the filtering function of the kidneys. In hemodialysis, a patient's blood is circulated into an external filter and cleaned. The filtered blood is then returned to the body. In peritoneal dialysis, a fluid containing dextrose is introduced into the abdomen through a tube. This solution absorbs the wastes in the body and is then removed.
• Pain medications: Many OFD I patients with polycystic kidney disease experience pain. Pain medications, such as aspirin or acetaminophen, may be used to manage this symptom.
• Surgery: In some patients who experience severe pain with polycystic kidney disease, surgery may be performed to reduce the size of the cysts growing on the kidneys. This surgery does not provide a cure for the condition, as the cysts grow back. Surgery can also be used to correct a cleft palate or lip.
• Transplantation: Some patients who experience kidney failure may undergo kidney transplantation. Kidneys that are transplanted into patients with OFD I do not develop cysts. However, transplantation is associated with complications, including infection and the possibility of rejection of the new organ. To reduce the chance of rejection, patients may need to take immunosuppressant drugs.

• Currently, there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of orofaciodigital syndrome type I (OFD I). The therapies listed below have been studied for related conditions, 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.

C

Unclear or conflicting scientific evidence

• Magnet therapy
  : The use of magnets to treat illness has been described historically in many civilizations. In modern times, magnetic fields play an important role in Western medicine, including use for magnetic resonance imaging (MRI), pulsed electromagnetic fields, and experimental magnetic stimulatory techniques. A few case reports show that incorporation of dental magnets into dentures may be useful for patients with limited ability to tolerate or control removable dentures. Further research is needed to confirm these results.
• Avoid with implantable medical devices such as heart pacemakers, defibrillators, insulin pumps, or hepatic artery infusion pumps. Avoid with myasthenia gravis or bleeding disorders. Avoid if pregnant or breastfeeding. Magnet therapy is not advised as the sole treatment for potentially serious medical conditions, and should not delay the time to diagnosis or treatment with more proven methods. Patients are advised to discuss magnet therapy with qualified healthcare providers before starting treatment.

• General: Because orofaciodigital syndrome type I (OFD I) is inherited or occurs spontaneously, there is currently no known way to prevent the disease. However, a number of options are available for patients with family histories of OFD I.
• Genetic testing and counseling: Individuals who have OFD I may meet with a genetic counselor to discuss the risks of having children with the disease. Genetic counselors can explain the options and the associated risks of various tests, including pre-implantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS). These tests may have limited availability, especially for rare conditions like OFD I.