Marshall-Smith syndrome is a childhood condition involving specific facial characteristics, bone maturation that is advanced for the individual's age, failure to grow and gain weight appropriate for the individual's age, and severe respiratory (breathing) problems.
Marshall-Smith syndrome (MSS) was first described in two males seen in 1971 by Drs. Marshall, Graham, Scott, and Smith. They noticed changes in the skeletal system of these patients. Bones normally mature through several stages, naturally progressing through these stages with time. Specifically, a young child's bones have more cartilage and less calcium deposits than an adult's bones. A child's bones appear less "dense" on an x ray than an adult's bones. A constant feature of MSS is skeletal maturation that is advanced for age. For example, in 1993 a newborn child with MSS was found to have the "bone age" of a three year-old child.
Specific facial features in MSS include a wide and prominent forehead, protruding and widely spaced eyes, a very small chin, and a small, upturned nose. Because individuals may not gain weight or grow well, they are often smaller than other children of the same age. There are often problems with structures in the respiratory tract (such as the larynx and trachea) and this can lead to difficulty with breathing. Pneumonia, or a lung infection, is common because of this; these can occur several times.
Significant mental and physical delays are almost always expected in MSS. Since children with MSS are often hospitalized for long periods of time to help treat respiratory problems, they may also be slower to do physical things like crawling or walking.
No two patients with MSS have the exact same symptoms, as there is some variability with the condition. There are no alternate names for Marshall-Smith syndrome, though it is sometimes incorrectly referred to as Weaver syndrome , a separate condition with similar symptoms.
Families with MSS can be put under a great deal of stress, because long-term hospitalizations in the intensive care unit are common for children with MSS.
The vast majority of people with MSS are unique in their family; there is usually no family history of the condition. Because of this, MSS is thought to be a random, sporadic event when it occurs. No specific gene has been associated with MSS, and other genetic background is still largely unknown. Standard genetic testing , such as chromosome analysis and metabolic studies, typically are normal for patients with MSS.
In 1999, a group in Saudi Arabia reported a young girl with features of MSS who had a chromosome abnormality. She was found to have some duplication of the material on a region of chromosome 2. This has led researchers to believe that the gene for MSS may actually be on chromosome 2. This is the only individual with MSS found to have a chromosome abnormality. Current research is under way to determine the exact genetic cause for MSS.
Marshall-Smith syndrome is very rare in the general population. In fact, no statistical rates are available for the condition. It appears to be present across the world, affecting males and females equally.
Signs and symptoms
The most medically serious complication in MSS is the associated respiratory problems. Structures in the respiratory system, such as the larynx and trachea, may not function properly because they can be "floppy," soft, and less muscular than usual. Because of this, airways can become plugged or clogged, since air does not move through to clear them like usual. Mucus may start collecting, causing an increased amount of bacteria that can lead to pneumonia. Ear infections are common, because the bacteria can spread to the ears as well. Internal nasal passages may be narrower in people with MSS, which can also pose difficulty with breathing.
Children with MSS may have problems with eating, due to similar reasons that they may have difficulty breathing. Additionally, they may have a weak "suck" and "swallowing" reflex, normally controlled by muscular movements. As mentioned earlier, another feature of MSS is lack of proper growth and weight gain. This can be in part due to the difficulty in feeding for these individuals, though they are often very small even at birth.
Advanced bone age is present in all people with MSS. In particular, the bones of someone with MSS appear more dense on an x ray than they should, according to their age. While x rays of their hands and wrists often determine a person's "bone age," people with MSS often have a generalized advanced bone age within their entire skeleton. They may also have broad middle phalanges of the hand, which can be seen on an x ray.
Facial characteristics of people with MSS include those mentioned earlier, but other features may also occasionally be present. These can be blue-tinged sclerae (the white sections of the eyes), a large head circumference (measurement around the head), and a small, triangle-shaped face (with the point of the triangle being at the chin).
Occasionally, creases in the hands are "deeper" than usual in people with MSS. The first ("big") toe can also be longer and bigger than usual. Additional features include hirsuitism and an umbilical hernia. Hearing loss can sometimes occur. Ears may be larger, have a "crumpled" appearance, or be lower on the head than usual.
Changes in the brain can occur in MSS. An individual was reported in 1997 to have a smaller optic nerve (the nerve the connects the eyes to the brain) than usual, and had some vision problems as a result. Some children may be missing the corpus callosum, a structure in the brain. Mental and physical delays are commonly present in MSS, and are usually quite significant. These may in part be due to the brain abnormalities that are sometimes seen. There may be partial to complete lack of speech for individuals with MSS, another sign of the mental delays.
Because there is no genetic testing available for Marshall-Smith syndrome, all individuals have been diagnosed through a careful physical examination and study of their medical history.
Advanced skeletal age can be seen on x rays of the patient's hands and wrists, since this is the typical way to assess bone age. A full x ray survey of the body is a good way to assess age of other bones as well. Advanced bone age is always seen in Marshall-Smith syndrome, but it may also be present in other genetic syndromes. Sotos syndrome involves similar skeletal findings, but individuals are generally larger than usual and can have mental delays. Weaver syndrome includes advanced skeletal maturation, but individuals are often larger than usual and have other specific facial characteristics (such as very narrow, small eyes). These and other conditions can be ruled out if the respiratory complications and facial characteristics seen in MSS are not present.
Treatment and management
As mentioned earlier, long hospitalizations are common for people with MSS. Most of these involve treating severe respiratory complications of MSS. These types of complications often necessitate placing a tracheotomy to assist with breathing. Manual removal of the mucus buildup by suctioning near the tracheotomy is common. Frequent pneumonia is common, and intravenous antibiotics are often the treatment, as in people without MSS. There is no specific treatment for the advanced bone age.
Because feeding can be difficult for children with MSS, a gastrostomy is often needed, and feeding is done directly through the gastrostomy tube. It is a challenge to make sure children with MSS maintain proper growth, and sometimes a gastrostomy is the only way to achieve this.
Marshall-Smith syndrome is considered a childhood condition because affected individuals do not typically survive past childhood. There is no long-term research on the disease due to it being rare and not typically present in adults.
Most children with MSS die in early infancy, often by three years of age, largely due to severe respiratory complications, and infections that may result from them. There have been reports of children surviving until age seven oreight, but these children did not have severe respiratory problems. These children give hope that the condition is variable, and not every person diagnosed with the condition will have a severely shortened life span.
Little People's Research Fund, Inc. 80 Sister Pierre Dr., Towson, MD 21204-7534. (800) 232-5773 or (410) 494-0055, Fax: (410) 494-0062. <http://pixelscapes.com/lprf>.
"Marshall-Smith syndrome." Health Library. <http://hvlib.integris-health.com/Library/HealthGuide/IllnessConditions>.
Deepti Babu, MS, CGC