Marshall-Smith syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at September 6, 2016
StartDiseasesMarshall-Smith syndrome

An individual with Marshall-Smith syndrome (MSS) will experience rapid physical growth along with bone development. The accelerated growth may begin before birth, and symptoms include respiratory problems, intellectual disability, and physical deformities. Failure to thrive is a common symptom, and people with this disorder typically have high mortality rates.

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Definition & Facts

Despite the rapid development of bones, individuals with this syndrome typically fail to thrive and will be underweight for their overall size. They are slow to develop gross motor skills and fine motor skills, and brain abnormalities are possible. The exact cause is unknown, and treatments focus on addressing the related symptoms.

According to the Marshall Smith Syndrome Research Foundation, the first diagnosed case was in 1971. Since that time, roughly 50 children and adults have been diagnosed. The condition is so rare that comprehensive statistical information does not exist for it.

Symptoms & Complaints

The disorder is serious and can result in life-threatening complications. One of the greatest concerns is respiratory problems. Individuals with this syndrome may make high-pitched noises when breathing, and their tongues may obstruct their air passages. It is also common for them to hyperextend their necks beyond the normal and safe limits. Bone fractures are also common with this disorder.

Another physical deformity may present in the epiglottis which is a flap in the larynx that prevents food and liquids from entering the windpipe (trachea) and opens during eating to allow food into the esophagus. People with Marshall-Smith syndrome may not have a properly developed flap, and that increases the risk that they will choke on their food.

Weakened immune systems are also common, so they are at a higher risk of infections and other complications. They may also have smaller optic nerves and vision problems as a result of MSS.

In addition to excessive bone development, another common symptom is excessive hair growth or hirsutism. People with MSS may have a marked physical appearance with a prominent forehead and eyes, a low nasal bridge, and upturned nose. They typically have long faces, and the whites of their eyes (sclera) may appear bluish.

Their hands are also unique with broad bones in the first finger segments and smaller fingertips. They have poor life expectancy, and most children suffering with this disorder will not survive past the age of two years.

Causes

MSS is present before birth, and boys and girls are affected at the same rate. Most people with MMS will be the only ones in their families to have this condition.

Researchers have found the gene for MMS, yet it is not passed from parent to child. It appears to be a random, spontaneous mutation with any one group having the same risk as another. Some researchers are defining it as a new dominant mutation due to the rarity and randomness of identified cases.

The gene associated with MMS has been identified and named: the NFIX gene. Parents who currently have a child with MMS can have more children without worrying that they will also have the disorder. This is a spontaneous genetic mutation, and it is highly unlikely to occur twice in the same family; that is, there is typically no family history associated with the syndrome.

Diagnosis & Tests

Diagnosis is made through careful examination by a doctor. The medical history will also be reviewed. The accelerated skeletal growth is most commonly seen in the hands and wrists, but a full X-ray may be done to determine the age of bones throughout the body.

In the case of infants, the symptoms may be more readily visible because the young child will appear much older physically. A baby that’s only a few weeks old can appear to be over a year old due to the rapid bone growth. Additionally, children who have unexplained fractures before the age of five may be checked for this condition.

Physicians may also ask about the milestones that young infants reach. Children with Marshall-Smith syndrome typically do not reach the normal milestones, and they will have delays in walking and crawling as a result of their physical challenges or intellectual disability.

Doctors typically look for a triad before making this diagnosis. In addition to the accelerated bone development, they will also check for failure to thrive and the syndrome's characteristic facial deformities. There are other diseases that feature advanced bone development, so doctors may also look for these other symptoms to ensure that the diagnosis is correct.

There are several related medical conditions that physicians may decide to look for or rule out. These include Greig cephalopolysyndactyly syndrome, psychomotor retardation, and polysyndactyly.

Treatment & Therapy

Many people with MMS will face long periods of hospitalization in their lives. There is no treatment for the syndrome itself, so the medical community will focus on managing and controlling the associated symptoms. Early aggressive management of the feeding and respiratory problems may improve the overall prognosis for patients.

The breathing difficulties may result in patients receiving a tracheotomy to normalize breathing. Mucus and fluid can build up in this area and will have to be suctioned out frequently. Pneumonia commonly occurs due to the defective flap above the windpipe, and it is typically treated with IV antibiotics to fight the infection.

Feeding can also be difficult, and the constant threat of choking leads many patients to have a feeding tube inserted directly into the stomach. This eliminates the risk of choking while still allowing the patient to receive the necessary nutrition.

Support groups have developed through the internet, so families of individuals who are struggling with this disorder can share stories and resources.

Prevention & Prophylaxis

There is no cure for this syndrome, and it cannot be prevented. In the past, people with the disorder would not survive past three years of age, but this is improving with the ability to better treat the symptoms and prevent choking and other respiratory problems. Currently, some patients with MMS have survived into adulthood. It is unknown what can be expected as this population ages.