SCIENTIFIC BACKGROUND

17p11.2

Category:

Scientific background

Smith-Magenis syndrome (SMS) is a global developmental delay disorder associated with typical behaviors and discrete external features, such as brachycephaly, flat midface, broad nasal bridge, M-shaped curved upper lip with distinct philtrum, brachydactyly, and forearm limitations in infancy and early childhood. The voice is often low and hoarse. Up to 70% of patients have hearing loss, often as a result of chronic middle ear infections (80-90%). About 30% have congenital malformations of the heart and/or kidneys. Foot deformities are common. Approximately 50% have myopia and occasionally related retinal detachment. Tantrums, self-harming behavior and significant sleep disorders are typical in SMS and can be very stressful for families. Many children with SMS are described as musical and most are good with computers, which can be used for support. The prevalence is reported to be 1:15,000 to 1:25,000. However, SMS is probably underdiagnosed.

 

SMS is caused by a microdeletion of variable size (ranging from 1.5 to 9 Mb, usually about 3.7 Mb) on the short arm of chromosome 17 (17p11.2) involving the RAI1 gene in 90% of cases and a pathogenic variant in the RAI1 gene in 10% of cases. The RAI1 gene is responsible for most of the symptoms of SMS. An additional 13 genes located in the deleted region modify the severity (contiguous gene syndrome). The microdeletion or variant almost always occurs de novo. Consequently, the risk of recurrence is low if a parental chromosomal structural change in chromosome 17 or a rare parental mosaic for a RAI1 variant have been ruled out. Large deletions can be found with conventional chromosomal analysis, and the more common small ones with FISH analysis or a chromosomal microarray.

 

References

Nag et al. 2019, J Intellect Disab 23(3):359 / Goldenberg 2018, Pediatr Ann 47(5):e198 / Elsea et al. 2008, Eur J Hum Genet 16:412 / Rost 2000, Monatsschr Kinderheilkd 148:55 / Greenberg et al. 1996, Am J Med Genet 62:247

GENES

17p11.2
How to order

LATEST ARTICLES

Duchenne muscular dystrophy, a rare inherited muscle disorder characterized by progressive muscle weakness and degeneration that leads to difficultie...

Read more

May 12 is International Nurses Day. It is celebrated on Florence Nightingale’s birthday. She pioneered the field of modern nursing through her dedi...

Read more

Hair loss is a common problem that affects millions of men and women around the world. While genetics is believed to be the most significant factor c...

Read more

Depression is a serious mental health issue affecting over 280 million people worldwide. Recent research has revealed a potential link between gut he...

Read more

If you are unlucky enough to suffer from migraines, you will know that a migraine is not just a bad headache. The headache and accompanying symptoms ...

Read more

Autism spectrum disorder (ASD) is a neurological developmental disorder that affects brain development and function. This affects how people learn, b...

Read more

Researchers have developed a method called "Mendelian Phenotype Search Engine" (MPSE) to identify which sick infants in the neonatal intensive care u...

Read more

Did you know that wisdom teeth are actually an evolutionary leftover from our ancient ancestors that no longer serve their original purpose? These mo...

Read more

Azoospermia is a medical condition characterized by the absence of sperm in the ejaculate and is a major cause of male infertility. It affects 1 in 1...

Read more

Science has traditionally been a male dominated subject; however, women have also been hard at work in this field for decades. We put together this i...

Read more