Oculodentodigital dysplasia

Oculodentodigital dysplasia is a genetic condition affecting the eyes, teeth, and fingers, with symptoms that vary widely among affected individuals.

Overview

Oculodentodigital dysplasia is a condition that affects many parts of the body, particularly the eyes (oculo-), teeth (dento-), and fingers (digital). The signs and symptoms of the condition vary widely among affected individuals. Some features of oculodentodigital dysplasia are evident at birth, while others become apparent with age.

People with oculodentodigital dysplasia often have eye abnormalities that can lead to vision loss. These eye problems can include underdeveloped and small eyes (microphthalmia) and clouding of the lenses of the eyes (cataracts). People with oculodentodigital dysplasia may also have a condition called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.

The tooth abnormalities seen in people with oculodentodigital dysplasia often include missing or small teeth, weak enamel, and early tooth loss.

The condition can also affect the fingers and toes. Individuals with oculodentodigital dysplasia may have permanently bent fingers (camptodactyly), fingers that are unusually curved (clinodactyly), webbing of the skin (syndactyly) between the fourth and fifth fingers.

Individuals who have oculodentodigital dysplasia may also have abnormalities of the head and face (craniofacial anomalies), which can include a narrow nose, a small head size (microcephaly), and an opening in the roof of the mouth (cleft palate).

Less common features of oculodentodigital dysplasia include sparse hair growth (hypotrichosis); brittle nails; and a skin condition called palmoplantar keratoderma that causes the skin on the palms of the hands and the soles of the feet to become thick, scaly, and calloused.

Approximately 30 percent of people with oculodentodigital dysplasia experience neurological problems such as a lack of bladder or bowel control (incontinence), difficulty coordinating movements (ataxia), abnormal muscle stiffness (spasticity), and impaired speech (dysarthria). Some affected individuals develop abnormalities of the brain’s white matter that can be detected with medical imaging (leukodystrophy). Hearing loss and heart problems have also been reported in people with oculodentodigital dysplasia.

Frequency

The exact prevalence of oculodentodigital dysplasia is unknown. It has been diagnosed in fewer than 1,000 people worldwide, although it is likely that some affected individuals never receive a diagnosis.

Causes

Many different variants (also called mutations) in the GJA1 gene cause oculodentodigital dysplasia. The GJA1 gene provides instructions for making a protein called gap junction alpha-1 protein, which is commonly known as connexin 43. This protein is a building block for important channels called gap junctions. These channels are found on the cell surface and allow direct communication between cells. Gap junctions that contain connexin 43 proteins are found in many cells throughout the body.

Most of the GJA1 gene variants that cause oculodentodigital dysplasia result in the substitution of one protein building block (amino acid) for another in the connexin 43 protein. These altered proteins disrupt the structure or function of the gap junction channels. As a result, communication between cells is impaired. Lack of cell communication early in development likely interferes with normal cell growth and cell specialization. These two processes determine the shape and function of many different parts of the body. These developmental problems cause the signs and symptoms seen in people with oculodentodigital dysplasia.

Gene Associated with Oculodentodigital Dysplasia

• GJA1

Inheritance

Most cases of oculodentodigital dysplasia are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Some cases of this condition result from new (de novo) variants in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

Rarely, oculodentodigital dysplasia is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.