Information on the following diseases can be found in the Related Disorders section of this report:

• Waardenburg Syndrome

Telecanthus With Associated Abnormalities is apparent at birth. The more obvious signs are very widely spaced eyes (hypertelorism) that may be crossed or misaligned (strabismus) combined with a high broad nasal bridge (telecanthus). This is often accompanied by difficulty in swallowing due to an impairment of the esophagus (esophageal dysmotility), urinary tract deformities such as the opening of the urethra set very low on the underside of the male penis (hypospadias) or opening into the vagina of females. Often the testicles of the affected males are undescended (cryptorchidism). There may be clefting of the palate (laryngotracheal clefts), lips and back of the mouth (uvula) and often patients show one or more congenital heart defects (coarctation of the aorta). Approximately 38 percent of affected males experience mental retardation.
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The genetic origins of Telecanthus With Associated Abnormalities are complicated. The people who study the genetic origins of disorders characterized by skeletal anomalies (dysmorphologists) appear to have agreed that there are at least two forms of TCAA. Type I is thought to be an X-linked form and Type II is thought to exhibit autosomal dominance in hereditary transmission, with the defective gene located on Chromosome 22 at 22q11.2. (Autosomal means that the disorder is caused by a problem on a chromosome other than those labeled X or Y, the sex chromosomes).

Chromosomes, which are present in the nucleus of human cells, carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13 refers to band 13 on the short arm of chromosome 11.

X-linked disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a 50 percent risk of transmitting the carrier condition to their daughters, and a 50 percent risk of transmitting the disease to their sons.

In X-linked dominant disorders, the female with only one X chromosome affected will develop the disease. However, the affected male always has a more severe condition. Sometimes, affected males die before birth so that only female patients survive.

In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The risk is the same for each pregnancy.

Further complicating the genetic picture is the fact that there are several other disorders linked to 22q11.2 deletion. These include DiGeorge Syndrome, velocardiofacial syndrome, and conotruncal anomaly/face syndrome, among others. There is not yet a good explanation to explain these phenomena.
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Telecanthus With Associated Abnormalities affects males more often and more seriously than females.

Symptoms of the following disorders can be similar to those of Telecanthus With Associated Abnormalities. Comparisons may be useful for a differential diagnosis:

Waardenburg Syndrome is characterized by displacement of the inner folds of the eyelids, prominence of the nose, and overdevelopment of the eyebrows. The patient may have two different colored eyes or two colors in one iris of the eye. Congenital nerve deafness may also occur. A white streak of hair in the front (forelock) of the head or early greying of the hair may characterize this disorder. A thin nose with flaring nostrils, a "cupid bow" configuration of the lips, wide-set eyes, inflammation of the tear sac and drooping of the upper eyelids may occur. A lack of an indent between the nose and the forehead, prominent lower jaw and a clefted or high-arched palate may also be present. (For more information on this disorder, choose "Waardenburg" as your search term in the Rare Disease Database.)
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Diagnosis
Ultrasonography of the fetus as early as 19 weeks of pregnancy usually will show signs of abnormally widely spaced eyes and eyebrows.

Treatment
Telecanthus With Associated Abnormalities is usually treated by corrective surgery. Such surgery may include reconstructive surgery to correct the spacing between the eyes as well as straightening the eyes themselves. Surgical correction of the urinary deformities as well as the cleft palate, lips and uvula may also be recommended. If heart deformities are present, surgery may be necessary.

Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 145410; Last Update: 6/27/02 (mini-MIM).

TEXTBOOKS
Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:132-35.

Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:792-96.

JOURNAL ARTICLES
Fryburg JS, Lin KY, Golden WL. Chromosome 22q11.2 deletion in a boy with Opitz (G/BBB) syndrome. Am J Med Genet. 1996;62:274-75.

Robin NH, Opitz JM, Muenke M. Opitz G/BBB syndrome: clinical comparisons of families linked to Xp22 and 22.q, and a review of the literature. Am J Med Genet. 1996;62:305-17.

Zackai EH, McDonald-McGinn DM, Driscoll DA. Respiratory symptoms may be the first presenting sign of a 22q11.2 deletion: a study of vascular rings. (Abstract). Proc Greenwood Genet Center. 1996;15:137.

Verloes A, David A, Odent S, et al. Opitz GBBB syndrome: chromosomal evidence of an X-linked form. Am J Med Genet. 1995;59:123-28.

McDonald-McGinn DM, Driscoll DA, Bason L, et al. Autosomal dominant ‘Opitz’ GBBB syndrome due to a 22q11.2 deletion. Am J Med Genet. 1995;59:103-13.

Robin NH, Feldman GJ, Aronson AL, et al. Opitz syndrome is genetically heterogeneous with one locus on Xp22 and a second locus on 22q11.2. Nature Genet. 1995;11:459-61.

Guion-Almeida ML, Richieri-Costa A. CNS midline anomalies in the Opitz G/BBB syndrome: report on 12 Brazilian patients. Am J Med Genet. 1992;43:918-28.

Leichtman LG, Werner A, Bass WT, et al. Apparent Opitz BBBG syndrome with partial duplication of 5p. Am J Med Genet. 1991;40:173-76.