This is a growth disorder characterized by dwarfism, skeletal abnormalities and characteristic facial features. This syndrome is named after the three researchers who identified this condition and hence is also known as the 3M syndrome. The individuals affected continue to grow extremely slowly before and after birth reaching an average adult height of around 4 feet to 4 feet 6 inches. These people exhibit normal sized head and their intelligence remains normal as well. Most of the affected children are born with the respiratory problem which can be life-threatening in infancy.
Causes
This condition develops as the result of a mutation in the gene identified as CUL7 which produces a protein known as cullin-7. This protein is essential for the naturally degrading process of the unwanted proteins. The cullin-7 protein assembles the complex that is known as an E3 ubiquitin ligase that is responsible for the tagging of excess or damaged proteins which are then degraded and disposed. The ubiquitin-proteasome system is the cell machinery that controls the disposing of the proteins that are not required such as the misshaped or the damaged proteins. This system is also responsible for the regulation of the level of proteins that are involved in various activities of the cell such as the timing of cell division and their growth. The genetic mutation disrupts the function of the cullin-7 protein. This condition is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell from the parents are defective.
Symptoms
The symptoms of this condition include low birth weight, short stature, malformations of the head and the face, digital or skeletal abnormalities and delayed bone age. In most cases, the low birth weight is associated with the delayed growth during fetal development which can continue after birth resulting in short stature. The distinctive abnormalities of the head include a prominent forehead, triangular face, prominent pointed chin, large ears, underdeveloped upper jaw bones and abnormally crowded together teeth. The skeletal problems include malformations of the spinal column bones, abnormally smallness of hip bones and spine bifida which is the incomplete closure of certain bone of the spinal cord.
Diagnosis
In some of the cases, the characteristic features of this condition can be detected prenatally by ultrasound. In most cases, this syndrome is evident shortly after the birth based on the identification of features associated with this condition and with various specialized tests. The X-rays images can detect various craniofacial malformations and the skeletal abnormalities of this condition. Molecular genetic testing responsible for the mutation of the gene can confirm the diagnosis of this syndrome.
Treatment
The treatment of 3M syndrome is based on the symptoms evident in each case. The skeletal abnormalities may require the surgery or orthopedic techniques as treatment options. To correct the craniofacial, digital and other abnormalities, supportive measures or surgery may be required. An additional form of treatment is providing supportive care. In some cases, the genetic counseling may be beneficial for some of the affected individuals and their family members.
References
https://rarediseases.org/rare-diseases/three-m-syndrome/
https://ghr.nlm.nih.gov/condition/3-m-syndrome#inheritance
https://rarediseases.info.nih.gov/diseases/5667/3m-syndrome
