3M syndrome is a rare, inherited disorder that primarily impacts physical growth. Its name is derived from the initials of the three researchers—Miller, McKusick, and Malvaux—who first identified the condition. Also known by other names like Dolglen, Le Merrer, or Glazman syndrome, it is defined by significant short stature that begins before birth. Individuals with this syndrome often have a low birth weight despite being carried to full term, and their intellectual development is normal.
The Genetic Basis of 3M Syndrome
The cause of 3M syndrome is genetic. It is inherited in an autosomal recessive pattern, meaning an individual must receive a mutated gene from both parents to have the condition. The parents are carriers who have one copy of the mutated gene but do not show signs of the syndrome. This inheritance pattern explains why the disorder can appear in a family with no prior history of it.
Three genes have been identified as the cause of 3M syndrome when mutated: CUL7, OBSL1, and CCDC8. These genes provide instructions for making proteins involved in the body’s growth processes. A mutation in any of these genes disrupts the regulation of cell growth and division, which is the underlying reason for the significant growth restriction.
Primary Physical Characteristics
The most prominent feature of 3M syndrome is severe growth restriction. This begins in the womb, a condition known as intrauterine growth restriction, and results in a low birth weight. The slow growth continues throughout infancy, childhood, and adolescence, leading to a final adult height that is significantly below average. Despite the short stature, the body is proportional.
Individuals with 3M syndrome also have distinctive facial features. In infancy, these can include:
- A long, narrow head
- A flat midface
- Thick eyebrows
- A fleshy tip of the nose
- Full lips
As a child grows, their face often becomes more triangular with a pointed chin. Large ears and a prominent forehead are also common.
Beyond stature and facial features, the syndrome is associated with specific skeletal abnormalities. The long bones in the arms and legs are unusually thin and slender. X-rays may reveal that the bones of the spinal column are long and thin, and the neck can appear short and broad. Other findings include prominent heels and squared shoulders.
The Diagnostic Process
Diagnosing 3M syndrome begins with a clinical examination. A physician assesses the individual’s physical traits for the characteristic features, such as short stature and distinctive facial and skeletal markers. The presence of these signs at birth can suggest the disorder, and growth restriction may even be detected via ultrasound before birth.
Following the physical evaluation, radiological studies like X-rays are used to identify the specific skeletal abnormalities. These images can reveal slender long bones, the shape of the vertebrae, and other changes to the ribs and shoulder blades that are characteristic of the condition.
The definitive step in diagnosis is molecular genetic testing. This involves analyzing a blood sample for mutations in one of the three associated genes. Finding a pathogenic variant in one of these genes provides a conclusive diagnosis and helps distinguish 3M syndrome from other growth disorders.
Syndrome Management and Long-Term Outlook
There is no cure for 3M syndrome, so management focuses on monitoring health and addressing symptoms as they arise. Care is handled by a multidisciplinary team of specialists, including pediatricians, endocrinologists, and orthopedic surgeons. Regular check-ups track development and manage complications, and a hip ultrasound is often recommended for newborns to screen for hip dysplasia.
Unlike many other growth disorders, growth hormone treatment is not an effective therapy for the short stature associated with 3M syndrome. For males, an endocrine assessment at puberty may be recommended to check gonadal function. Physical therapy can be beneficial for improving mobility and managing joint-related problems.
The long-term outlook for individuals with 3M syndrome includes a normal lifespan. The primary challenges are related to the physical limitations from severe short stature. Supportive care and adaptive aids can help manage these challenges and improve quality of life. Females with the syndrome are reported to have normal ovarian function.