Related Terms

• Alopecia, anodontia, ectodermal dysplasia, eye defects, GAPO, growth retardation, inherited genetic condition, optic atrophy.

Background

• Growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) 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 syndromes are genetic disorders that can be inherited, or passed down among family members, in an autosomal dominant or recessive manner. GAPO syndrome is hypothesized to be autosomal recessive, based on parental consanguinity (parents who are genetically related) and case reports of affected siblings.

• The GAPO phenotype is characteristically progressive in nature and may be attributed to the accumulation of extracellular connective tissue matrix.

• Symptoms of GAPO affect the hair, teeth, eyes, skin, and face. Specifically, GAPO syndrome is characterized by reduced birth length, alopecia (hair loss from the scalp or body), failure of the teeth to erupt from the gums, and loss of some or all of the fibers of the optic nerve, a condition known as optic atrophy. The optic nerve carries visual information from the eye to the occipital lobe in the brain, which then processes the information. In addition, physical growth is delayed. Symptoms such as reduced birth length can be observed at birth.

• GAPO syndrome is a rare, inherited genetic disorder. Scientists first described the syndrome in 1947, since which time there has been the suggestion of a potential founder effect.

• The genetic mutation or defect that causes GAPO syndrome is located on one of the 22 pairs of autosomes. Because it is a recessive disorder, two copies of the defective gene, one from each parent, are necessary for the disease to appear. GAPO syndrome is extremely rare, with fewer than 30 known cases in the scientific literature. Its exact incidence is unknown, but parents who are consanguineous are more likely to have a child with GAPO syndrome. GAPO syndrome appears to affect males and females and all racial and ethnic groups equally.

• The life expectancy of people with GAPO syndrome may be reduced. In a report of adults with GAPO syndrome who died in their 30s or 40s, heart disease and other tissue changes were observed. The cause of this heart disease and tissue change is yet unknown. People with GAPO syndrome are generally of normal intelligence.

• There is no cure for GAPO syndrome. Instead, treatment aims to reduce symptoms and prevent or treat complications.

Risk Factors

• Because growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome is inherited, the only known risk factor is a family history of the disease. GAPO syndrome 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: Growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome is a rare, inherited genetic disorder, meaning that is passed down among family members. The exact genetic mutation or defect that causes GAPO syndrome is unknown at this time.

• Autosomal recessive inheritance: GAPO syndrome is inherited as an autosomal recessive trait, meaning that an individual must inherit two copies of the defective recessive 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, 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 the disorder.

• Random occurrence: It is unknown whether GAPO syndrome 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 growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome. While the most common symptoms are hair loss, dental and eye problems, and growth delay, there is a wide array of other symptoms that have been observed in patients with GAPO syndrome.

• Eyes: Optic atrophy, or the breakdown of the fibers of the optic nerve, occurs in about 30% of people with GAPO syndrome. The optic nerve connects the eye to the occipital lobe in the brain, which is responsible for processing visual information. Optic atrophy may cause blurred vision, problems with peripheral vision, and reduced color vision. Additional features of GAPO syndrome may include widely spaced eyes, puffy eyelids, and sparse or absent eyebrows and eyelashes. In some people with GAPO syndrome, there may be vision loss.

• Face: People with GAPO syndrome have a distinctive facial appearance, including coarse features, a high or prominent forehead, an abnormal mid-face region, and the appearance of being older than their age. In addition, the chin may be small, the lips may protrude or be abnormally thick, and the ears may stick out or be low-set.

• Growth: Generally, bone development and growth are delayed in people with GAPO syndrome. This often results in short stature.

• Hair: Alopecia, or abnormal hair loss, is a common feature of GAPO syndrome. Hair on the head and other parts of the body tends to be sparse and may be brittle or absent.

• Teeth: Pseudoanodontia, or failure of the teeth to erupt and develop normally, is a common symptom of GAPO syndrome.

• Other: In some patients with GAPO syndrome, veins can be observed through the skin on the head, and the pulse can be heard through the scalp. Additional symptoms that may be associated with GAPO syndrome include loose skin, double jointedness, hernia, short fingers and toes, glaucoma (a buildup of pressure in the eye), delayed sexual development, skin lesions, and brain abnormalities.

• Although rare, other symptoms have been observed in individuals with GAPO syndrome. These include a detached retina, enlarged eyeballs, nearsightedness, involuntary eye movements, a poorly developed skull, deafness, skeletal defects, white eyelashes, irregular skin coloring, skin tumors, and kidney problems. These symptoms are rare in GAPO syndrome, so it is possible that another condition could be responsible for their presence.

Diagnosis

• General: Growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome may be suspected based on the observation of physical stature and the distinctive qualities of the head, face, hair, teeth, and eyes. Specifically, GAPO syndrome is characterized by reduced birth length, alopecia (hair loss from the scalp or body), optic atrophy (loss of some or all of the fibers of the optic nerve), and pseudoanodontia (the failure of the teeth to erupt from the gums). The optic nerve carries visual information from the eye to the occipital lobe in the brain, which then processes the information. In addition, physical growth is delayed. A detailed family history and complete physical exam should be completed. Diagnosis may be made as early as six months of age.

• Eye exam: A thorough examination by an ophthalmologist should be completed to assess the presence and degree of optic atrophy, as well as glaucoma, or pressure in the eye. An ophthalmologist will use an ophthalmoscope to look inside the eye. To assess glaucoma, an intraocular pressure measurement is done.

• Imaging: Cephalometry, which involves the measurement of the human head, may be used to determine fetal growth.

Complications

• Dental problems: People with growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome may experience dental problems due to poorly developed and missing teeth. These may include cavities and further tooth loss.

• Life expectancy: The life expectancy of people with GAPO syndrome may be reduced. In a report of adults with GAPO syndrome who died in their 30s or 40s, heart disease and other tissue changes were observed. The cause of this heart disease and tissue changes is yet unknown.

• Vision loss: Whether due to optic atrophy (breakdown of the fibers of the optic nerve), glaucoma (increased pressure in the eye), or other rare eye problems, people with GAPO syndrome may experience loss of vision.

Treatment

• Corrective lenses: Individuals with growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome may benefit from corrective lenses or glasses to correct vision problems such as nearsightedness. However, neither glasses nor corrective lenses can improve optic atrophy (breakdown of the fibers of the optic nerve), which is common in GAPO, nor can they improve glaucoma (increased pressure in the eye), involuntary eye movements, or a detached retina, which are rare but do occur in this syndrome.

• Corticosteroids: The use of corticosteroids, a class of steroid hormones used to treat a variety of conditions with inflammation, has been studied to treat optic atrophy in GAPO syndrome, but their use remains controversial. There remains no treatment for optic atrophy.

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

Integrative Therapies

• Currently there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome.

Prevention

• Because growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome is inherited, there is no known means of preventing the disorder. Currently, genetic tests are not available for GAPO syndrome. However, genetic counselors may be able to help prospective parents with GAPO syndrome understand the potential of passing the condition on 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

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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