NORD gratefully acknowledges Paula Goldenberg, MD, MSW, MSCE, Massachusetts General Hospital for Children, for assistance in the preparation of this report.
Marshall syndrome is a rare autosomal dominant genetic disorder caused by mutations in the COL11A1 gene. Major symptoms may include a distinctive face with a flattened nasal bridge and nostrils that are tilted upward, widely spaced eyes, nearsightedness, cataracts and hearing loss.
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 dome-like upper portion of the skull (calvaria) is thicker than normal and calcium deposits can be found in the skull (cranium). Frontal sinuses may be absent. 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 than 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 a rare autosomal dominant genetic disorder caused by mutations in the collagen XI, alpha-1 polypeptide (COL11A1) gene located on chromosome 1p21.1. Typically mutations causing Marshall syndrome are splice site mutations involving base pair insertions or deletions of intron 50. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy.
One Saudi family has been reported with two sons with Marshall syndrome with homozygous missense mutations of COL11A1. In this family there was concern for possible autosomal recessive inheritance, as each parent carried one missense mutation with glycine substitution, and these parents had short stature, thick calvaria, and mild hearing loss with normal ophthalmologic examination and did not have a diagnosis of Stickler or Marshall syndrome. Recessive genetic disorders occur when a child inherits two abnormal copies of a gene, one from each parent, who is unaffected. It may be in this family that both parents are mildly affected by Stickler syndrome and in this situation the inheritance would be termed double dominant. In either situation, the recurrence risk would be 25% with each pregnancy. The risk is the same for males and females.
Plastic surgery can improve saddle nose in Marshall syndrome. 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 is recommended for affected individuals 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. Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov.
All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in
Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Contact for additional information about Marshall syndrome:
Paula Goldenberg, MD, MSW, MSCE
Stickler Syndrome Clinic/ Genetics Clinic-Yawkey 6, MGH
Genetics Unit, Massachusetts General Hospital for Children
175 Cambridge Street-5th floor
Boston, MA 02114
Email: [email protected]
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