Smith-Magenis Syndrome

Classification according to ICD-10
Q93.5	Other deletions of a part of a chromosome
ICD-10 online (WHO version 2019)

The Smith-Magenis syndrome ( SMS ) is a rare genetic disease , the loss of a piece (micro deletion ) of material on the short arm of chromosome 17 (17p11.2 del) in the human genome originated and is one of the microdeletion syndromes .

Microdeletion syndrome 17p11.2 is a synonym for SMS.

root cause

Smith-Magenis syndrome is a genetic syndrome in which the affected person lacks a small piece of chromosome 17 and thus the genetic information available there . This lack is described in medicine as deletion 17p11.2 . The "p" for "petit" (= small) stands for the short arm of the chromosome. Since the missing piece can be of different lengths, the syndrome can be very different.

The missing region contains several different genes. According to previous studies, however, the loss of a certain gene, RAI1 , is primarily responsible for the typical symptoms of the syndrome. The other missing genes may help explain why the individual difference in the expression of traits is so great. Studies are ongoing to establish a connection between the size of the information loss and the severity of the symptoms.

Case studies are known in which people with Smith-Magenis syndrome do not have a deletion but only a mutation in the RAI1 gene. These changes to the RAI1 gene or its loss probably leads to the production of a non-functioning RAI1 protein, the actual function of which has not yet been clarified.

According to the current state of knowledge, the Smith-Magenis syndrome develops spontaneously and cannot be directly traced back to misconduct during pregnancy or to environmental influences. The mutation of the 17th chromosome occurs accidentally and even before fertilization during the formation of the egg or sperm . The mutation can occur in the father or in the mother. The children of a parent whose genome shows the deletion do not automatically get the syndrome, but can also be born completely healthy.

According to American studies, the disease occurs with a frequency of 1: 25,000 births, but only individual case studies are known in German-speaking countries.

Symptoms

• Learning disabilities , cognitive disabilities ( IQ 20–78, mostly 40–54)
• Developmental delay
• short stature
• underdeveloped (flat) middle face
• protruding lower jaw
• Cleft lip and / or cleft palate
• downward curved mouth
• unusually shaped ears
• chronic ear infections
• linguistic delay
• deep, hoarse voice
• Hearing impairment
• myopia
• Retinal detachment
• Strabismus (squint)
• Brushfield spots
• small, broad hands; short fingers and toes
• Heart defect , heart murmur
• Kidney, ureter and bladder problems
• Scoliosis (lateral curvature of the spine)
• Hypotonia (weak muscles), unusually thin lower legs
• noticeable gait (sequence of steps)
• deep tendon reflexes difficult to trigger
• decreased sensitivity to pain
• disturbed temperature sensation
• Difficulty chewing
• sensitive scalp
• sometimes considerable difficulty falling asleep and staying asleep, often very tired during the day
• Behavioral disorders, e.g. E.g .: hyperactivity , self-injurious behavior such as hitting the head against walls etc., biting the hands, pecking at skin and scars, pulling off fingernails and toenails, introducing foreign bodies into ears and nose, outbursts of anger, destructive and aggressive behaviors, Excitability, self-hugging / hand squeezing when excited.
• Behaviors such as B. observed in many people with autism (fear of being touched, inability to speak, strong need for routine and uniformity in everyday life)

diagnosis

The typical symptoms of Smith-Magenis syndrome are insufficient for a reliable diagnosis. There are syndromes that are relevant for differential diagnosis and are quite similar to SMS, e.g. B. the Prader-Willi syndrome . A mere counting or viewing of the chromosomes alone is also not sufficient to be able to ensure the diagnosis. A genetic test called fluorescence in situ hybridization ( FISH test ) must therefore be carried out in order to obtain a reliable result . Blood cells, which can be obtained as part of a normal blood sample, are examined for the absence of certain sections of chromosome 17. Due to the new investigations into the RAI1 gene, it seems essential to carry a specific probe for RAI1 . Further research on this subject is certainly still necessary.

The small number of people with SMS is probably also explained by the fact that the syndrome is often not diagnosed as such, and the children often receive a different - similar - diagnosis, such as autism or attention deficit / hyperactivity disorder ( ADHD ).

Differential diagnosis

To be delimited is u. a. the Kleefstra syndrome (9q34 deletion syndrome), but other syndromes such as Down syndrome , Williams syndrome , microdeletion 2q37 , Prader-Willi syndrome , 22q11 deletion syndrome or Sotos syndrome differential diagnosis clarified.

treatment

Due to the genetic cause, a cure is not possible, so therapy refers to treating the symptoms. Therapies such as physiotherapy , occupational therapy or speech therapy can be helpful . Communication training with sign language or GuK can also be helpful. Often people with Smith-Magenis syndrome are dependent on help and therapy for life.

There are currently some approaches to drug therapy, but here too the interventions are limited to alleviating the symptoms, not eliminating the cause. For example, the sleep problems of some people could be improved by the evening administration of melatonin , other drugs (such as Risperdal ) can be used to dampen self-injurious behavior.

history

The syndrome was scientifically described in the early 1980s by geneticists Ann Smith and Ellen Magenis and named after them.

literature

• Ann CM Smith, R. Ellen Magenis, Sarah H. Elsea: Overview of Smith-Magenis Syndrome. In: The Journal of the Association of Genetic Technologists. 31 (4) 2005, PMID 16354942
• Ann CM Smith: Two Decades Since Discovery - An Interdisciplinary Approach to Understanding Smith-Magenis Syndrome (SMS) . Lecture at the SMS meeting 2006, Heidelberg, [1]
• Andrea L. Gropman, Wallace C. Duncan, Ann CM Smith: Neurologic and Developmental Features of the Smith-Magenis Syndrome (del 17p11.2). In: Pediatric Neurology. Vol. 34 No. 5, PMID 16647992
• Andrea L. Gropman, Sarah Elsea, Wallace C. Duncan Jr, Ann CM Smith: New developments in Smith-Magenis syndrome (del 17p11.2). In: Current Opinion in Neurology . 2007, 20, pp. 125-134, PMID 17351481
• Hélène De Leersnyder, Marie Christine de Blois, Jean Louis Bresson, Daniel Sidi, Bruno Claustrat, Arnold Munnich: Inversion du rythme circadien de la mélatonine dans le syndrome de Smith-Magenis. In: Revue neurologique. 2003; Vol 159 (11), pp. 6S21-6S26, PMID 14646795

Individual evidence

1. ↑ JA Raeburn et al: What is Smith-Magenis Syndrome ?. The Smith-Magenis Syndrome Foundation, London 1999.
2. ↑ Association for self-help, information and advice in dealing with Smith-Magenis-Syndrom eV (Sirius): http://www.smith-magenis.de/was-ist-sms/symptome/
3. ↑ INSERM US14-- ALL RIGHTS RESERVED: Orphanet: Smith Magenis Syndrome. Retrieved April 8, 2019 . 

Web links

• Parents and Researchers Interested in Smith-Magenis Syndrome - the American society around SMS
• the website of the German association SIRIUS SIRIUS = self-help, information and advice in dealing with the Smith-Magenis syndrome
• the Austrian information site on Smith-Magenis syndrome
• Smith-Magenis Syndrome.  In: Online Mendelian Inheritance in Man . (English).
• Smith-Magenis Syndrome . In: Orphanet

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !