What is Three M syndrome?
Three M syndrome is a rare genetic syndrome that causes skeletal abnormalities primarily. Slow growth is also a defining characteristic of the syndrome and this slow growth continues throughout childhood and into adulthood. There are currently around 100 reported cases of the syndrome worldwide.
A variant of the syndrome known as Yakut short stature syndrome has been reported in the isolated Yakut population in Siberia, Russia. This variant of the syndrome also presents with breathing difficulties and issues that can be life-threatening in infancy.
This syndrome is also known as:
3M Syndrome; Dolichospondylic Dysplasia; Gloomy Face Syndrome; Le Merrer Syndrome; Slender boned nanism
What gene changes cause Three M syndrome?
Changes in the CUL7 gene are responsible for the majority of cases of the syndrome, around ¾ of all diagnosed cases are caused by this particular gene. Around 16% of cases of the syndrome are caused by mutations in the OBSL1 gene. And some patients have been found to have mutations in the CCDC8 gene, although there are probably other unidentified genes remaining.
The syndrome is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms but have a 25% chance of passing the copies of the gene mutations onto each of their children.
What are the main symptoms of Three M syndrome?
- Very slow growth is a defining characteristic of the syndrome, and this continues into adolescence. Generally affected individuals do not grow taller than 4 feet to 4 feet 6 inches.
- Unique facial features of the syndrome can vary. Some individuals have a head that measures a normal size but which looks larger in proportion to the rest of the body. In other individuals, their head may be unusually long and narrow.
- Other facial features include a triangular face, a broad and prominent forehead, pointed chin, a sunken midface, large ears, full eyebrows, an upturned nose and a long philtrum, prominent mouth and full lips.
An abnormal curving of the spine is another feature of the syndrome, as is the curving of the fingers.
Possible clinical traits/features:
Postnatal growth retardation, Short stature, Depressed nasal bridge, Short 5th finger, Hypospadias, Short ribs, Hypoplastic pelvis, Hyperlordosis, Scapular winging, Short thorax, Slender long bone, Spina bifida occulta, Frontal bossing, Thick eyebrow, Triangular face, Thick lower lip vermilion, Short neck, Pes planus, Pointed chin, Autosomal recessive inheritance, Intellectual disability, Intrauterine growth retardation, Mandibular prognathia, Pectus excavatum, Long philtrum, Increased vertebral height, Joint hypermobility, Neonatal respiratory distress, Anteverted nares, Malar flattening, Decreased testicular size, Delayed skeletal maturation, Small for gestational age, Clinodactyly of the 5th finger, Hip dislocation, Dolichocephaly.
How is it diagnosed?
To find out if someone has a diagnosis of Three M syndrome, it is important to have a consultation and evaluation with a clinical genetic specialist. Specialists may also suggest specific genetic testing or other types of tests to help reach a diagnosis. FDNA’s AI technology can help speed up the diagnostic process by analyzing facial features and other health information.
