Osteosclerosis and ectodermal dysplasia

Related Terms

Cote-Katsantoni syndrome, ectodermal dysplasia, inherited genetic disease, osteosclerosis.

Background

Osteosclerosis and ectodermal dysplasia, also known as Cote-Katsantoni syndrome, is 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. Ectodermal dysplasias are genetic disorders that can be inherited in an autosomal dominant or recessive manner.
Symptoms of osteosclerosis and ectodermal dysplasia include atrial septal defect, low levels of neutrophils, growth delays, and intellectual disabilities.
Osteosclerosis and ectodermal dysplasia is an inherited genetic disorder, meaning that is passed down from family members. The exact genetic mutation or defect that causes this condition is unknown, as are the inheritance pattern and incidence of the disorder.
Osteosclerosis and ectodermal dysplasia is extremely rare, with only a few reported cases in the scientific literature. There is a lack of information on the life expectancy of individuals with osteosclerosis and ectodermal dysplasia.

Signs and symptoms

General: Osteosclerosis is a condition in which the bones become abnormally dense. Other symptoms of ectodermal dysplasia include atrial septal defect, a heart condition that allows blood to flow freely between the left and right atria of the heart, as well as growth delay, intellectual disabilities, and an increased susceptibility to infection.
Blood: People with osteosclerosis and ectodermal dysplasia tend to have decreased levels of neutrophils, a type of white blood cell. The role of neutrophils is to protect the body from infection; therefore, a person with low levels may be more susceptible to infections from bacteria and viruses.
Bones: The main symptom of Cote-Katsantoni syndrome is osteosclerosis. In osteosclerosis, bone density is abnormally high. Associated symptoms include fractures, anemia, and bone pain. The hands and feet may be poorly developed. The fingers and toes may be abnormally curved.
Digestive: People with osteosclerosis and ectodermal dysplasia may not be able to absorb important nutrients from the digestive tract, a condition known as malabsorption. Malabsorption can lead to vitamin and mineral deficiencies, weight loss, and chronic diarrhea.
Eyes: As is true for people with other forms of ectodermal dysplasia, people with osteosclerosis and ectodermal dysplasia may have eye problems, including abnormally small eyes.
Growth: Individuals with osteosclerosis and ectodermal dysplasia have delayed growth and may be of short stature. Developing fetuses with osteosclerosis and ectodermal dysplasia may experience growth delays prior to birth.
Hair: The hair tends to be sparse and brittle. It may break off at a short length or be completely absent. In addition, body hair, eyelashes, and eyebrows tend to be sparse or missing.
Heart: Individuals with osteosclerosis and ectodermal dysplasia have a heart defect known as atrial septal defect. This is essentially a hole in the muscle wall that separates the two atria in the heart. If the hole is large, oxygen-rich blood may leak from the left atrium back into the right, causing the heart to work inefficiently. Symptoms of an atrial septal defect include decreased exercise tolerance, fatigue, and heart palpitations.
Nails: The nails on the fingers and toes may be poorly developed and be ridged or grooved.
Skin: Individuals with osteosclerosis and ectodermal dysplasia develop a skin disorder called ichthyosis. Because ichthyosis causes the skin to have a scaled look, it is sometimes referred to as fish-skin disease.
Teeth: People with osteosclerosis and ectodermal dysplasia may have poorly developed teeth, including abnormal tooth enamel, which can lead to frequent cavities.
Other: Some people with osteosclerosis and ectodermal dysplasia have intellectual disabilities.

Diagnosis

General: Osteosclerosis and ectodermal dysplasia may be suspected from the observation of distinctive characteristics of the hair, nails, skin, eyes, and teeth. Osteosclerosis and ectodermal dysplasia is characterized by atrial septal defect, low levels of neutrophils, and intellectual disabilities. In addition, a complete physical and thorough family history should be completed. There is a lack of information on when this condition is typically diagnosed.
Biopsy: A biopsy of the skin may be done in patients suspected of having osteosclerosis and ectodermal dysplasia to assess the hair follicles and skin texture. A biopsy entails the removal of a small tissue sample for examination in a lab.
Blood tests: A small sample of blood may be taken to obtain a neutrophil count. Neutrophils are a type of white blood cell that protects the body from infection. Blood tests may also assess whether the individual has decreased levels of various vitamins and minerals in the blood because of malabsorption, the inability to absorb nutrients in the digestive tract. Diagnosis of osteosclerosis and ectodermal dysplasia cannot be based solely on these signs, because decreased absorption of vitamins and minerals and decreased levels of neutrophils may indicate several other conditions.
Echocardiogram: An echocardiogram (ECG) allows a clinician to assess the presence and extent of atrial septal defect, a heart condition that allows blood to flow freely between the left and right atria of the heart. An ECG can also produce accurate assessment of the velocity of blood and cardiac tissue at any point using pulsed- or continuous-wave Doppler ultrasound. This test allows assessment of cardiac valve areas and function, any abnormal communication between the left and right sides of the heart, and any valvular regurgitation (leaking of blood through the valves), and calculation of the cardiac output.
Genetic tests: Currently no genetic tests are available to aid in the diagnosis of osteosclerosis and ectodermal dysplasia, because the causative genetic mutation has not yet been identified.
Imaging: Imaging studies such as X-rays may help clinicians assess overall growth and health of the bones in the hands, feet, and other parts of the body. Doctors can use X-rays to determine areas of increased bone density.
Stool sample: If malabsorption is suspected, a clinician may collect a stool sample for analysis. If a patient has malabsorption, the stool may contain different levels of certain substances that are normally absorbed in the intestine, such as fat.

Complications

Dental problems: Because of poorly developed teeth and defects in tooth enamel, people with osteosclerosis and ectodermal dysplasia are prone to frequent cavities and tooth loss.
Heart problems: Individuals with osteosclerosis and ectodermal dysplasia may have a heart defect known as atrial septal defect. This is essentially a hole in the muscle wall that separates the two atria in the heart. If the hole is large, oxygen-rich blood may leak from the left atrium back into the right, causing the heart to work inefficiently. Symptoms of an atrial septal defect include decreased exercise tolerance, fatigue, and heart palpitations.
Malnutrition: Individuals with osteosclerosis and ectodermal dysplasia may not absorb a sufficient amount of vitamins and minerals from food. This condition is known as malabsorption. Malabsorption can cause various vitamin and mineral deficiencies. Common problems associated with malabsorption include fatigue, dizziness, weight loss, and decreased immune response.
Osteosclerosis: Osteosclerosis refers to the abnormal hardening of the bones or bone marrow, causing bone density to be abnormally high. Symptoms associated with osteosclerosis include fractures, anemia, and bone pain. The hands and feet may be poorly developed, and the fingers may be abnormally curved.
Recurrent infections: Depending on the level of neutrophils, patients with osteosclerosis and ectodermal dysplasia may develop recurrent infections. These infections occur commonly in the mouth, ears, tonsils, throat, and lungs.

Treatment

General: There is no cure for osteosclerosis and ectodermal dysplasia. Instead, treatment is focused on the reduction of symptoms and prevention of complications.
Vitamin and mineral supplementation: Individuals with osteosclerosis and ectodermal dysplasia may suffer from malabsorption, the inability to absorb nutrients in the digestive tract. Depending on the individual needs of a patient with malabsorption, vitamin and mineral supplements may be recommended. These may include single-nutrient supplements, such as vitamin C, or combination supplements, such as a multivitamin with minerals
Dental care: Patients with osteosclerosis and ectodermal dysplasia must practice good oral hygiene, including flossing, brushing, and regular visits to the dentist.
Drugs: Antibiotics may be used to treat bacterial infections.
Corticosteroids are a class of drugs that mimic hormones produced by the adrenal glands. Corticosteroids such as prednisone help control immune function and may help increase the number of neutrophils in the blood. Treatment with corticosteroids is associated with side effects, including increased infections and development of diabetes. Other side effects of corticosteroids include glaucoma (elevated pressure in the eyes); fluid retention that can cause swelling in the lower legs; increased blood pressure; mood swings; and weight gain, with fat deposits in the abdomen, face, and the back of the neck.
Over-the-counter and prescription drugs may be used to treat ichthyosis, a condition that causes the skin to have a scaled appearance. Skin softeners such as petroleum or mineral oil and retinoids, derivatives of vitamin A, may improve the appearance and texture of skin. Minor adverse effects of retinoids include dryness and cracking of the skin, temporary hair loss, and dryness of the eyes, mouth, and nostrils. Severe adverse effects of retinoids may include liver damage, increased blood cholesterol levels, excessive bone growth, birth defects, headache, and swelling of the brain. People taking retinoids should be regularly monitored for these adverse effects. In addition, women of childbearing age should undergo regular pregnancy tests if using retinoids.
Education: The law requires that individuals with osteosclerosis and ectodermal dysplasia have access to an education that is tailored to their needs. According to the Individuals with Disabilities Education Act, all children with disabilities in the United States must receive free and appropriate education from age three until the end of high school or until the person is 21 years old, whichever occurs first.
If a child has intellectual disabilities, staff members of the patient's school should consult with the patient's parents or caregivers to design an individualized education plan. 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 severity of the person's intellectual and learning disabilities. In general, most experts believe that children with disabilities should be educated alongside their nondisabled peers. It is believed that the nondisabled students will help the patient learn appropriate behavioral, social, and language skills. Depending on specific needs, patients with intellectual disabilities may be educated in mainstream classrooms, attend public schools but take special education classes, or attend specialized schools that are equipped to teach children with disabilities.
Surgery: Atrial septal defect, a heart condition seen in osteosclerosis and ectodermal dysplasia, is essentially a hole in the muscle wall that separates the two atria of the heart. If the hole is large, oxygen-rich blood may leak from the left atrium back into the right, causing the heart to work inefficiently. If an atrial septal defect is detected and assessed, it may be corrected by surgery. Surgical closure of an atrial septal defect involves opening up at least one atrium and closing the defect with a patch.
Colony-stimulating factors: Neutropenia is a condition characterized by a low number of neutrophils, a type of white blood cell. Neutrophils are white blood cells that are responsible for protecting the body against infections. If the number of neutrophils is decreased, an individual may become more susceptible to infections. An individual affected by osteosclerosis and ectodermal dysplasia who develops neutropenia may benefit from taking a protein called granulocyte colony-stimulating factor (G-CSF). G-CSF is a growth factor produced by human cells to stimulate cell production. Although people with neutropenia appear to produce their own G-CSF, this does not appear to sufficient. Adding extra G-CSF may help increase the number of neutrophils in the blood. G-CSF is given by injection and is the preferred treatment for neutropenia. The recombinant human G-CSF (filgrastim) is synthesized in an E. coli expression system, which uses bacteria to grow proteins for medicinal uses. The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Filgrastim (Neupogen?) and PEG-filgrastim (Neulasta?) are two commercially available forms of rhG-CSF (recombinant human G-CSF). Although rare, side effects include fever, rapid or irregular heartbeat, wheezing, and sores on the skin from the injections.
Transfusion: In some cases, low levels of neutrophils may be treated by transfusion of neutrophils from a donor. This procedure is used only in life-threatening situations and when other approaches have failed. Risks associated with transfusion include a reaction to the transfused blood products. This reaction may result in chills, headache, backache, chest pain, tachycardia, and hypotension. Rarely, blood products can sometimes be contaminated with bacteria, and there is a chance that a virus may be transmitted to the recipient. Screening of blood products has made viral transmission rare in blood transfusion.
Bone marrow transplant: A bone marrow transplant is an option for people with severely decreased levels of neutrophils. Bone marrow is a spongy tissue found inside bones. The bone marrow in the breastbone, skull, hips, ribs, and spine contains stem cells that produce the body's blood cells. These blood cells include leukocytes (white blood cells), which fight infection; erythrocytes (red blood cells), which carry oxygen; and platelets, which enable the blood to clot. A bone marrow transplant, also called a stem-cell transplant, is a procedure in which diseased or damaged bone marrow cells are replaced with healthy ones. This procedure carries a number of risks, including rejection of the transplant, and it is recommended only when other approaches have failed.

Integrative therapies

Currently there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of osteosclerosis and ectodermal dysplasia.

Prevention

Genetic testing and counseling: Individuals who have osteosclerosis and ectodermal dysplasia 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 preimplantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS). These tests may have limited availability, especially for rare conditions such as osteosclerosis and ectodermal dysplasia. Osteosclerosis and ectodermal dysplasia may be inherited or caused by a spontaneous mutation, although the genetic mutation that may cause osteosclerosis and ectodermal dysplasia is unknown. However, genetic counselors may be able to help prospective parents who have or have a family history of the condition to understand the risks of passing on the disorder to their children.

Author information

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

Bibliography

Blau EB. Ectodermal dysplasia, osteosclerosis, atrial septal defect, malabsorption, neutropenia, growth, and mental retardation: the Cote-Katsantoni syndrome? Am J Med Genet 1987 Mar;26(3):729-32.
Civitelli R, McAllister WH, Teitelbaum SL, et al. Central osteosclerosis with ectodermal dysplasia: clinical, laboratory, radiologic, and histopathologic characterization with review of the literature. J Bone Miner Res 1989 Dec;4(6):863-75.
Cote GB, Katsantoni A. Osteosclerosis and ectodermal dysplasia. Prog Clin Biol Res 1982;104:161-2.
Ectodermal Dysplasia Society. .
National Foundation for Ectodermal Dysplasias. .
Natural Standard: The Authority on Integrative Medicine. .

Causes

General: The genetic mutation or defect that causes osteosclerosis and ectodermal dysplasia is currently unknown. Since information on the prevalence of osteosclerosis and ectodermal dysplasia is lacking, the likelihood of having a child with this condition is unclear. It is also unclear whether any particular race, ethnicity, or sex is affected more often than others.

Risk factors

Because osteosclerosis and ectodermal dysplasia is inherited, the only known risk factor is a family history of the disorder.