3-M syndrome

3-M syndrome (alternative names: dolichospondylic dysplasia, gloomy face syndrome and le Merrer syndrome) is a rare hereditary growth retardation syndrome.^[1][2] The name 3-M originates from the initials of the three authors Miller, McKusick and Malvaux who first reported the syndrome in literature.^[1] Major symptoms of 3M syndrome are dwarfism, facial dysmorphia and skeletal abnormalities.^[1][3] No signs of mental retardation are reported.^[1] 3-M syndrome is thought to be inherited as an autosomal recessive genetic trait.^[1][4][5]

Diagnosis

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. DNA banking is particularly relevant in situations in which molecular genetic testing is available on a research basis only. No laboratories offering molecular genetic testing for prenatal diagnosis of 3-M syndrome are listed in the GeneTests Laboratory Directory. However, prenatal testing may be available for families in which the disease-causing mutations have been identified in an affected family member in a research or clinical laboratory.^[6]

Causes

3-M syndrome is thought to be inherited as an autosomal recessive genetic 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 recessive disorders, the condition does not occur unless an individual inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. (Again, in the case of 3-M syndrome, some carriers may exhibit some mild symptoms associated with the disorder.) The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but usually will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy. Individuals who carry a single copy of the defective gene for 3-M syndrome (heterozygotes) may exhibit some mild physical findings associated with the disorder (e.g., subtle craniofacial abnormalities and/or unusually slender bones).^[7]

Symptoms

3-M syndrome is an extremely rare inherited disorder that appears to affect males and females in equal numbers. Approximately 25 cases have been reported in the medical literature since the disorder was first described in 1972. Many of the symptoms and physical features associated with the disorder are apparent at birth (congenital). In some cases, individuals who carry a single copy of the disease gene (heterozygotes) may exhibit mild symptoms associated with 3-M syndrome.^[7]

Treatment

In most cases, 3-M syndrome is diagnosed shortly after birth, based upon a thorough clinical evaluation, identification of characteristic physical findings (e.g., low birth weight, short stature, characteristic craniofacial and skeletal malformations, etc.), and/or a variety of specialized tests, such as advanced imaging techniques. Specialized x-ray studies may detect, confirm, and/or characterize certain craniofacial malformations (e.g., dolicocephaly, maxillary hypoplasia) as well as other skeletal abnormalities often associated with the disorder such as distinctive malformations of the vertebrae, the long bones, the ribs, and/or the shoulder blades. Identification of the gene that causes 3-M syndrome may eventually lead to molecular genetic testing to confirm a suspected diagnosis. The treatment of 3-M syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who specialize in treating skeletal disorders (orthopedists), dental specialists, and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment. In some cases, orthopedic techniques, surgery, and/or other supportive techniques may be used to help treat certain skeletal abnormalities associated with 3-M syndrome. Surgery and/or supportive measures may also be used to help treat or correct certain craniofacial, digital, and/or other abnormalities associated with the disorder. In addition, in affected individuals with dental abnormalities, braces, oral surgery, and/or other corrective techniques may be used to help treat or correct such malformations. Genetic counseling will be of benefit for affected individuals 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 3-M syndrome or heterozygosity for the disorder. Other treatment for 3-M syndrome is symptomatic and supportive.^[7]

Molecular genetics

3-M syndrome was linked to mutations of the Cullin7 gene that encodes a component of the Cullin7 E3 ubiquitin ligase.^[8]

References

External links

• GeneReviews/NIH/NCBI/UW entry on 3-M syndrome
• OMIM entries on 3-M syndrome