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

• Spondyloepiphyseal Dysplasia Congenita
• Congenital Syphilis
• Stickler Syndrome
• Wagner Syndrome

Patients with Marshall Syndrome have a distinctive flat sunken midface with a flattened nasal bridge (saddle nose), nostrils that turn upward, and a wide space between the eyes (hypertelorism). The domelike upper portion of the skull (calvaria) is thicker than normal and calcium deposits can be found in the skull (cranium). Eye defects found in patients with Marshall Syndrome are nearsightedness, a disease of the eye in which the lens loses its clarity (cataract), and a wide space between the eyes making the eyeballs appear to be larger then normal. Hearing loss may range from slight to severe; the distortion of the sound is a consequence of the nerve damage (sensorineural).

Other symptoms exhibited by some patients with Marshall Syndrome are: crossed eyes (esotropia), a condition in which the line of vision is higher in one eye than the other (hypertropia), retinal detachment, glaucoma, protruding upper incisors (teeth) and a smaller than normal or missing nasal bone.

Marshall Syndrome is inherited as an autosomal dominant 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. 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.

Marshall Syndrome affects males and females in equal numbers. Only about 21 cases of this disorder are reported in the medical literature.

Symptoms of the following disorders can be similar to those of Marshall Syndrome. Comparisons may be useful for a differential diagnosis:

Spondyloepiphyseal Dysplasia Congenita (SED Congenita) is a rare hereditary disorder with symptoms that can range from mild to severe. It is characterized by flat facial features, nearsightedness (myopia), retinal detachment, cleft palate, clubfoot, short-trunk dwarfism, a waddling gait and normally sized hands and feet. This disorder is inherited as an autosomal dominant trait. (For more information on this disorder, choose "Spondyloepiphyseal Dysplasia Congenita" as your search term in the Rare Disease Database.)

Congenital Syphilis is a chronic infectious disease caused by a spirochete (treponema pallidum) acquired by the fetus in the uterus. Symptoms of this disease may not show up until several weeks or months after birth and in some cases they may take years to appear. Congenital Syphilis is passed on to the child from the mother who acquired the disease prior to or during pregnancy. Symptoms of early congenital Syphilis include fever, skin problems and low birth weight. In Late Congenital Syphilis the symptoms of the disease do not usually become apparent until two to five years of age. Symptoms of Late Congenital Syphilis may be bone pain, peg-shaped upper central incisors (teeth), blurred vision, eye pain and insensitivity to light, saddle nose, bony prominence of the forehead, short upper jaw bone and deafness. In rare cases the disease may remain latent for years with symptoms not being diagnosed until well into adulthood. (For more information on this disorder, choose "Congenital Syphilis" as your search term in the Rare Disease Database.)

Stickler Syndrome is a rare genetic disorder inherited as an autosomal dominant trait. This disorder is characterized by congenital abnormalities of the eye, a small jaw and a cleft palate. Degenerative changes in some joints with bone abnormalities may occur early in life. In the past some scientists felt that Marshall Syndrome and Stickler Syndrome were the same disorder. It is now thought that there are distinct differences between the two. Patients with Stickler Syndrome have flat cheekbones and a small jaw which is often described as a flat midface. Patients with Marshall Syndrome have a retracted midface with abnormal frontal sinuses and calcification in the skull. Patients with Stickler Syndrome have a cleft palate while patients with Marshall Syndrome rarely are afflicted with this condition. Deafness is rarely a part of Stickler Syndrome and is often a major part of Marshall Syndrome. (For more information on this disorder, choose "Stickler Syndrome" as your search term in the Rare Disease Database.)

Wagner Syndrome is a rare disorder inherited as an autosomal dominant trait. This disorder can be expressed in mild, moderate or severe form. It is characterized by facial abnormalities, an underdeveloped jaw, saddle nose, cleft palate, and vision abnormalities. Joint hyperextensibility in the fingers, elbows and knees, and hip deformities may also occur. Patients with Wagner Syndrome do not have retinal detachment as do the patients with Marshall and Stickler Syndromes.

Since the cause of the disorder is unknown, the specific symptoms of Marshall Syndrome are treated; for example, plastic surgery can improve the saddle nose.

Other surgical procedures are used to remove the lenses of eyes affected by cataracts, after which lens implants are used as replacements. Subsequently, contact lenses may help improve sharpness of vision. Laser techniques are used to loosen any material, such as the cornea or the lens capsule, that may adhere to the lens.

The use of a hearing aid may be beneficial in some cases.

Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.

After the removal of the affected lens in children with congenital cataracts, an intraocular lens (IOL) may be implanted. If technically feasible, the IOL is implanted in the lens capsule. More research is needed before this implantation can be used more generally to preserve vision and reduce double vision.

TEXTBOOKS
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University Press; Entry No: 154780. Date Created: 6/2/86. Last Update Date:10/8/99

Jones KL., ed. Smith's Recognizable Patterns of Human Malformation, Philadelphia, PA: W.B. Saunders Co; 1997:252-53.

Buyse ML., ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications: for: Center for Birth Defects Information Services, Inc; 1990:504-5.

REVIEW ARTICLES
Shanske AL, et al., The Marshall syndrome: report of a new family and review of the literature. Am J Med Genet. 1997;70:52-57.

Reinert P, et al., [Periodic fever in the child. Survey of Marshall syndrome. Pediatric Infectious Disease Pathology Group]. Arch Pediatr. 1998;5(Suppl 2):198s-99s. French.

JOURNAL ARTICLES
Shanske AL, et al., Marshall syndrome and a defect at the COL11A1 locus. Am J Hum Genet. 1998;63:1558-61.

Griffith AJ, et al., Marshall syndrome associated with a splicing defect at the COL11A1 locus. Am J Hum Genet. 1998;62:816-23.

Schlote T, et al., [Lens coloboma and lens dislocation in Stickler (Marshall) syndrome]. Klin Monatsbl Augenheilkd. 1997;210:227-28.