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

• Cataracts, Inherited Congenital (General)
• Lenz Microphthalmia Syndrome

In affected males, the primary physical characteristic associated with Cataract-Dental Syndrome is the presence of dense clouding (opacities) of the lens of both eyes at birth (congenital bilateral nuclear cataracts). Such cataracts may result in blurred vision and severely decreased clearness or clarity of vision (visual acuity).

Males with Cataract-Dental Syndrome may have additional eye abnormalities. The front (anterior), clear portion of the eye through which light passes (cornea) may be unusually small (microcornea). In addition, affected males with poor vision may have recurrent, involuntary, "to-and-fro" movements of the eyes (pendular nystagmus) and/or abnormal deviation of one eye in relation to the other (strabismus). In some cases, the entire eye may be abnormally small (microphthalmia) and/or the upper eyelid may droop (ptosis).

Males with Cataract-Dental Syndrome may also have several dental abnormalities, such as extra front teeth (supernumerary incisors) that are tapered and "screwdriver shaped" (Hutchinsonian incisors), similar in appearance to a tooth abnormality often associated with Congenital Syphilis (i.e., Hutchinson's teeth). In some cases, affected males may have an extra (supernumerary), centrally located front tooth in the upper jaw. The tooth may be "cone shaped" with an abnormally short root (mesiodens). Such supernumerary incisors may prevent or disrupt the normal eruption of permanent incisors in some cases. In addition, some affected males may also have unusually wide spaces (irregular diastema) between some of the teeth.

In many males with Cataract-Dental Syndrome, other physical findings may also be present. The ears may be flared forward (anteverted) and unusually prominent, with folded lobes. In addition, the bones within the body of the hands (metacarpals) may be abnormally short (brachymetacarpia). Some affected males may also have an unusually large nose, a high nasal bridge, and/or other abnormalities.

Some males with Cataract-Dental Syndrome may also experience delays in the acquisition of skills requiring the coordination of muscular and mental activity (psychomotor retardation). In addition, some reports suggest that approximately 20 to 30 percent of affected males may have varying levels of mental retardation. In most such cases, mild to moderate mental retardation is present. However, in rare instances, profound mental retardation has been observed.

As mentioned above, females who carry a single copy of the disease gene for Cataract-Dental Syndrome (heterozygotes) may manifest some symptoms of the disorder. Such symptoms are usually milder and more variable than those associated with the fully expressed disorder. Affected females may have abnormally small corneas (microcornea) and/or Y-shaped clouding (opacities) in the back portion of the lens of the eyes at birth (congenital posterior sutural cataracts). Vision may be normal, or there may be slightly decreased clearness or clarity of vision (visual acuity). Without appropriate treatment, posterior sutural cataracts may progress to total clouding of the lens of the eyes (total cataracts) later in life. Some heterozygous females may also have dental abnormalities, such as "cone-shaped" front teeth (incisors) and/or unusually wide spaces (irregular diastema) between some of the teeth.
.

Cataract-Dental Syndrome is inherited as an X-linked recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

X-linked recessive disorders are conditions that result from changes (mutations) of a gene on an X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. In females, disease traits on the X chromosome can be "masked" by the normal gene on the other X chromosome. (For more, see below.) However, since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will likely be fully 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. Thus, in summary, because Cataract-Dental Syndrome is transmitted as an X-linked recessive trait, the disorder is usually fully expressed in males only.

As mentioned above, in females who carry a copy of a disease gene for an X-linked recessive trait, disease traits on the X chromosome may essentially be "masked" by the normal gene on the other X chromosome. More specifically, because only one functioning X chromosome is required in males and females, one of the X chromosomes in each cell of a female is essentially "turned off," usually in a random pattern (random X chromosome inactivation). Therefore, if the X chromosome with the gene mutation is activated in some cells, female carriers may manifest certain, typically more variable or mild features of the disorder as discussed above (see "Symptoms").

The gene responsible for Cataract-Dental Syndrome has been mapped to the short arm (p) of chromosome X (Xp22.31-p22.13). Chromosomes are found in the nucleus of all body cells. They 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 subdivided into bands that are numbered. Therefore, "Xp22.13" refers to band 22.13 on the short arm of chromosome X.
.


.

As discussed above, Cataract-Dental Syndrome is usually fully expressed in males only, although females who carry a single copy of the disease gene (heterozygotes) may manifest certain features. Since the disorder was described in 1974 in two extended families (kindreds), several additional kindreds have been reported in the medical literature. In addition to the name Cataract-Dental Syndrome, the disorder is sometimes referred to as Nance-Horan Syndrome. The latter term is derived from the names of investigators who first described the disease entity in detail.
.

Symptoms of the following disorders may be similar to those of Cataract-Dental Syndrome. Comparisons may be useful for a differential diagnosis:

There are several other rare inherited disorders in which clouding of the lens of the eyes at or shortly after birth (congenital or postnatal cataracts) occurs in association with other abnormalities of the eye. In some cases, the front (anterior), clear portion of the eye through which light passes (cornea) may be unusually small and/or the entire eye may be smaller than normal (microphthalmia). In addition, affected individuals may exhibit rapid, involuntary movements of the eyes (nystagmus); nearsightedness (myopia); crossing of the eyes (strabismus); and/or other abnormalities of the eyes. Visual impairment may range from slight to severe, depending upon the extent of cataracts and/or any additional eye abnormalities that are present. These rare cataract disorders are typically isolated and/or may be inherited as autosomal dominant, autosomal recessive, and/or X-linked genetic traits, depending upon the disorder in question. Such disorders include Congenital Cataract with Microcornea or Slight Microphthalmia; Total Congenital Cataract with Posterior Sutural Opacities in Heterozygotes; Cataract-Microcornea Syndrome; Cataract, Microphthalmia, and Nystagmus; and Microphthalmia-Cataract.

Lenz Microphthalmia Syndrome is an extremely rare inherited disorder characterized by abnormal smallness of one or both eyes (unilateral or bilateral microphthalmia) and/or droopy eyelids (blepharoptosis), resulting in visual impairment. In rare cases, affected infants may exhibit complete absence or rudimentary (vestigial) portions of the eyes (anophthalmia). Most affected infants also exhibit developmental retardation, ranging from mild to severe, as well as mental retardation. Additional physical abnormalities associated with this disorder may include an unusually small head (microcephaly); teeth that are widely spaced or abnormally crowded; ears that flare forward (anteverted) and/or are underdeveloped (hypoplastic); and/or malformations of the fingers and/or toes (digits). Some affected individuals may also exhibit incomplete closure of the roof of the mouth (cleft palate); a vertical groove in the upper lip (cleft lip); a sideways and front-to-back curvature of the spine (kyphoscoliosis); and/or abnormalities of the reproductive and urinary (genitourinary) tract, such as failure of the testes to descend into the scrotum in males (cryptorchidism) and/or underdevelopment (hypoplasia) or absence of a kidney (renal agenesis). Lenz Microphthalmia Syndrome, which is inherited as an X-linked genetic trait, is fully expressed in males only. However, females who carry one copy of the disease gene (heterozygotes) may exhibit some of the signs associated with the disorder, such as an abnormally small head (microcephaly) and/or malformations of the fingers and/or toes.

Diagnosis
Cataract-Dental Syndrome may be diagnosed based upon a thorough clinical evaluation, detection of characteristic physical findings, and specialized testing, including the use of an illuminated microscope to examine the interior of the eyes (slit-lamp examination) and dental x-ray series.

Treatment
The treatment of Cataract-Dental Syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists, such as pediatricians; physicians who diagnose and treat diseases of the eye (ophthalmologists); dental specialists who diagnose, prevent, and/or correct misalignment (malocclusion) and other abnormalities of the teeth (orthodontists); and other health care professionals.

A variety of methods may be used to treat, prevent, and/or correct eye defects associated with Cataract-Dental Syndrome, depending upon the specific combination of abnormalities present, their severity, and/or other factors. In affected males with cataracts, surgery may be recommended to remove the cataracts and, in some cases, to implant artificial lenses. In addition, corrective glasses, contact lenses, and/or other measures may be used to help improve vision.

Carrier females and at-risk females should receive regular examinations from an ophthalmologist to ensure early detection of eye abnormalities potentially associated with the disorder. In many cases, cataract surgery may be recommended to improve or preserve visual acuity.

In affected individuals with extra front teeth (supernumerary incisors), surgery may be advised to remove the additional incisors. Braces, dental surgery, and/or other corrective procedures may also be undertaken to correct other dental abnormalities, such as unusually wide spaces (diastema) between some of the teeth.

Early intervention is important in ensuring that affected children reach their potential. Special services that may be beneficial may include special remedial education and other medical, social, and/or vocational services.

Genetic counseling will be of benefit for affected individuals, at-risk females, and their families. Family members of affected individuals should also receive regular clinical evaluations to detect any symptoms and physical characteristics that may be potentially associated with Cataract-Dental Syndrome or heterozygosity for the disorder. Other treatment for this disorder is symptomatic and supportive.
.

Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 302350; 11/7/94. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?302350.

TEXTBOOKS
Behrman RE, et al., eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:1783-84.

Gorlin RJ, et al, eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:866-868.

Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:290-91, 294, 296, 1043-44, 1652.

JOURNAL ARTICLES
Walpole SM, et al. Exclusion of RAI2 as the causative gene for Nance-Horan syndrome. Hum Genet. 1999;104:410-11.

Montini E, et al. Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region. Genomics. 1998;51:427-33.

Toutain A, et al. Nance-Horan syndrome: linkage analysis in 4 families refines localization in Xp22.31-p22.13 region. Hum Genet. 1997;99:256-61.

Franco E, et al. Nance-Horan syndrome: a contiguous gene syndrome involving deletion of the amelogenin gene? A case report and molecular analysis. Oral Dis. 1995;1:8-11.

Bergen AA, et al. Nance-Horan syndrome: linkage analysis in a family from the Netherlands. Genomics. 1994;21:238-40.

Stambolian D, et al. Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis. Am J Hum Genet. 1990;47:13-19.

Zhu D, et al. Assignment of the Nance-Horan syndrome to the distal short arm of the X chromosome. Hum Genet. 1990;86:54-58.

Walpole IR, et al. The Nance-Horan syndrome. J Med Genet. 1990;27:632-34.

Lewis RA, et al. Mapping X-linked ophthalmic diseases. IV. Provisional assignment of the locus for X-linked congenital cataracts and microcornea (the Nance-Horan syndrome) to Xp22.2-p22.3. Ophthalmology. 1990;97:110-20, Discussion 120-21.

Lewis RA. Mapping the gene for X-linked cataracts and microcornea with facial, dental, and skeletal features to Xp22: an appraisal of the Nance-Horan syndrome. Trans Am Ophthalmol Soc. 1989;87:658-728.

Seow WK, et al. The Nance-Horan syndrome of dental anomalies, congenital cataracts, microphthalmia, and anteverted pinna: case report. Pediatr Dent. 1985;7:307-11.

Bixler D, et al. The Nance-Horan syndrome: a rare X-linked ocular-dental trait with expression in heterozygous females. Clin Genet. 1984;26:30-35.

van Dorp DB, et al. A family with X-chromosomal recessive congenital cataract, microphthalmia, a peculiar form of the ear and dental anomalies. J Pediatr Ophthalmol Strabismus. 1979;16:166-71.

Horan MB, et al. X-linked cataract and Hutchinsonian teeth. Aust Paediat J. 1974;10:98-102.

Nance WE, et al. Congenital X-linked cataract, dental anomalies and brachymetacarpalia. Birth Defects. 1974;10:285-91.