Oculodentodigital syndrome

Definition

Oculodentodigital syndrome (ODDS) is a relatively rare genetic condition with specific medical findings involving the eyes, skeletal system, brain, dentition, and face.

Description

Most fully described by the German ophthalmologist Dr. Gerard Meyer-Schwickerath and others in 1957, today ODDS is also known as oculodentodigital dysplasia , oculodentooseous dysplasia, and Meyer-Schwickerath syndrome.

People with ODDS experience symptoms differently. Overall, the symptoms usually affect the eyes, teeth, hands, feet, face, bones, hair, and brain.

Common signs of ODDS include a slightly indented nasal bone, thin nose with small nasal openings, thin and upturned nostrils, small eyes with iris abnormalities, small corneas, webbing of the fingers or toes, and weakened enamel on the teeth.

Genetic profile

ODDS is an inherited disorder caused by mutations in GJA1, also known as the connexin-43 gene . This gene is located on chromosome 6.

ODDS is most commonly inherited in an autosomal dominant pattern. In this type, family histories are common and the condition may be present in several generations. A person with ODDS has a 50% of having an affected child. The exact signs and symptoms may vary from person to person, even within the same family.

Instances of autosomal dominant inheritance with no family history also exist, in which a person develops ODDS from a new mutation that occurred by chance during their conception. There are reports of these chance mutations being possibly associated with an older average age for the father.

Rarely, ODDS has been reported to follow an autosomal recessive pattern of inheritance. In this type, there may be no family history and the condition may only show up in one generation. Two parents would have a 25% chance of having another affected son or daughter once their child is diagnosed with ODDS.

In 1997, Shapiro, et al., reported a unique family history of ODDS. In this family, relatives in successive generations had more severe neurological signs of ODDS than their older relatives, and these signs showed up at an earlier age in each successive generation. Loddenkemper, et al., described a similar family history in 2002, again involving neurological symptoms of ODDS. These patterns suggest the genetic phenomenon called anticipation, which has been described in other genetic conditions. The hallmark of anticipation is people with progressively worse symptoms in successive generations of the same family.

Demographics

ODDS occurs worldwide, affecting males and females equally. The exact incidence is not known, but it is not a common condition.

Signs and symptoms

Ocular and facial findings

Small, sunken eyes that are closer together or wider apart are common features in ODDS. Additionally, one's corneas may be smaller than normal. Other eye findings include glaucoma , cataracts, iris abnormalities, poor vision, and an extra fold of skin near the nose at the upper eyelid.

Facial characteristics of people with ODDS can be unique to them and their affected family members. A striking facial feature is the narrow, longer nose seen in the condition. People may also have narrow and upturned nostrils, a prominent jaw, and smaller head size.

Dental and mouth findings

A common dental finding of ODDS is weaker tooth enamel, making teeth prone to decay and cavities. People with ODDS may also be born with smaller teeth than normal, missing teeth, or have a premature loss of teeth. Cleft lip and cleft palate have also been seen in ODDS.

Skeletal and digital findings

People with ODDS can have enlargement of specific bones. These include bones in the hands, feet, ribs, and skull. This can cause the forearm to turn outward in some people. Some with the condition are prone to their hips dislocating.

The hands and feet of people with ODDS can be significantly affected. Some may have severe webbing between their fourth and pinky fingers, so much so that they look like one large, joined finger. The pinky finger may be shortened, curved, or permanently flexed as well. Webbing has also been seen between the third and fourth toes of people with ODDS.

Neurological findings

Less emphasis has been given to the neurological and other associated symptoms, though they can be very problematic for the person with ODDS. Some people with ODDS have very tight and stiff muscles with increased reflexes. This can result in difficulty with controlled muscle movements such as those needed for walking and speaking. Mental retardation is sometimes seen, and others may have muscle weakness of their limbs that can be similar to paralysis.

Brain changes are seen in people with ODDS. Examples of these are loss in the natural white matter and hardening within some brain structures.

Other findings

A common finding in ODDS is conductive hearing loss, which is usually related to sound waves not being able to travel through the normal ear pathways.

Thickening of the skin on the palms and soles of people with ODDS is common. It may be yellow-orange in color, but is not usually associated with blisters.

Another occasional finding in ODDS is very fine, dry hair. It may also be sparse and slower to grow than usual.

Diagnosis

Genetic testing from a blood sample is available for those suspected to have a clinical diagnosis. This testing studies the GJA1 gene carefully to look for disease-causing mutations. An abnormal genetic test result is one that finds a mutation in a person's copy of GJA1. Finding this mutation confirms the diagnosis of ODDS. Once a mutation has been found, other at-risk family members can also be tested. Genetic testing can also be offered during the second trimester of a pregnancy via an amniocentesis procedure, if a couple desires such information during that time.

Genetic testing should be offered in conjunction with careful genetic counseling for the affected individual, the family members, or the expectant couple.

A diagnosis is more often made after the careful identification and study of a person's symptoms and family history. A diagnosis may be suspected by a team of specialists, including an ophthalmologist, dermatologist, dentist, orthopedist, medical geneticist, neurologist, and otolaryngologist.

Treatment and management

Ocular and facial findings

The formation or appearance of the eyes cannot be treated and typically do not cause medical complications. Glaucoma, however, can lead to vision loss or blindness if left untreated. It may be treated with prescription eye drops, surgery, or laser treatments. The goal of glaucoma treatments is to reduce the pressure within the eye, thereby reducing the risk of damage to the eye structures and subsequent vision loss.

Some cataracts may be treated with surgery to remove the natural lens of the eye using various procedure options. The ophthalmologist will then replace it with a new, clear artificial lens. Some cataracts, especially those present at birth, may not be treatable and also may not cause serious vision problems for the person.

Facial characteristics seen in ODDS are not treatable and usually cause no medical complications.

Dental and mouth findings

People with ODDS have teeth that are prone to decay and cavities. Dentists can treat these to prevent further decay; teeth left untreated may need to be removed if the decay is too severe. Common treatment for cavities can include fillings, crowns, or root canal procedures in more complicated cases.

Those with a cleft lip may have it corrected with a surgery in the first few months of life. A cleft palate can be repaired through stages with surgery, often first happening in the first year of life. These surgeries usually require a multidisciplinary team consisting of a plastic surgeon, pediatric dentist, pediatric anesthesiologist, nurses, dietician/feeding specialist, and social worker.

Skeletal and digital findings

Many of the internal bone changes in people with ODDS cannot be treated. Those with significant webbing between their fingers and toes may find surgery helpful to gain mobility, the use of their digits, or cosmetic improvement. In cases where the bones are not webbed, surgery to separate the fingers or toes may be possible with the help of an orthopedic surgeon and plastic surgeon.

Children with hips that dislocate may require treatment with a harness or splint that keeps the hips in place. If this is not successful, a plaster cast may be necessary. Sometimes surgery by an orthopedic surgeon is needed to replace a hip in more severe cases.

Neurological findings

A magnetic resonance imaging (MRI) scan or other imaging study of the brain can document the changes sometimes seen in ODDS. Treatments may help those with increased muscle tone and problems with stiffness. Medications, physical therapy involving motion exercises, active stretching exercises, and occupational therapy can help. A combination of these is important in order for the person with ODDS to gain mobility and independence.

Mental delays and retardation may be assessed by a child development team or early childhood program. Extra assistance is sometimes available through early intervention programs and special education in schools. Social workers are useful to connect families to helpful resources.

Other findings

Hearing loss is best assessed and treated by an otolaryngologist and audiologist. Once determined as conductive hearing loss, treatments can include the use of antibiotics if an infection is present, ear drops, or hearing aids.

Skin changes are best assessed and treated by a dermatologist. Treatments may include the use of topical ointments or creams. Oral medications or carefully removing the outermost layer of skin to reduce thickness is helpful in some people. Treatments to change the hair texture or thickness is not usually necessary because it causes no medical complications.

A psychologist, genetic counselor, or therapist can be helpful for some with ODDS. Living with visible skin and digit changes can be difficult, and some may find it easier to talk to an objective person or to other families in a support group.

Prognosis

ODDS can involve a combination of severe medical complications in some cases. Since no two people experience the exact same type of symptoms, it is impossible to predict the ones a child newly diagnosed with the condition will have. No specific lifespan ranges are known, but might be lower in those who have more serious medical concerns. Newer medical treatments continue to offer hope for those with ODDS and their families.

Resources

BOOKS

Gorlin, Robert J., M. Michael Cohen, Jr., and Raoul C. M. Hennekam. Syndromes of the Head and Neck (OxfordMonographs on Medical Genetics, No. 42), Fourth Edition. Oxford University Press, 2001.

WEBSITES

Genetic Alliance. 2005 (March 15, 2005). <http://www.geneticalliance.org>.

Online Mendelian Inheritance in Man. (March 15, 2005.) <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM>.

ORGANIZATIONS

Oculo-Dento-Digital Dysplasia Support Group. 8810 Orchard Road, Pikesville, MD 21208. Phone: (410) 480-0882. Email: jquasneyjr@comcast.net. <http://home.comcast.net/~jquasneyjr>.

Deepti Babu, MS, CGC