Smith–Magenis syndrome

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

Cause

The Smith - Magenis syndrome is a genetically determined syndrome in which affected people a small piece of chromosome 17 and thus the genetic information present there is missing. This absence is described in medicine as deletion 17p11.2. The "p " as "petit " ( = small) stands for the short arm of the chromosome. As the missing piece may vary in length, the syndrome can vary widely pronounced.

The missing region contains several different genes. According to previous studies, however, is above all the loss of a particular gene, RAI1 responsible for the typical symptoms of the syndrome. The other missing genes may help to explain why the individual difference in the characteristic value is so great. It studies are underway to establish a relationship between the size of the information loss and the severity of their symptoms.

There are known the case examples, where people have with Smith - Magenis syndrome no deletion, but a mutation in the gene RAI1. These changes at the RAI1 gene or its loss will likely result in production of a non-functioning RAI1 protein, whose actual function is, however, not yet clarified.

The Smith - Magenis syndrome arises spontaneously according to current knowledge and is not a malfunction and during pregnancy nor to environmental influences directly traceable. The mutation of the 17th chromosome is formed at random and before fertilization of the oocyte, or during the formation of the sperm. The mutation can occur in the father or the mother. The children of a parent whose genetic material has the deletion get, not automatically the syndrome, but can also come completely healthy.

The disease is said to occur with an incidence of 1:25,000 births, according to American studies, yet only a few case examples are known in German-speaking documented.

Symptoms

  • Learning disability, cognitive disability (IQ 20-78, usually 40-54 )
  • Developmental delay
  • Short stature
  • Underdeveloped (flat ) midface
  • Of protruding lower jaw
  • Cleft lip and / or cleft palate
  • Downward curved mouth
  • Abnormally shaped ears
  • Chronic ear infections
  • Language delay
  • Deep, hoarse voice
  • Hearing loss
  • 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 (muscle weakness), unusual thin lower leg
  • Striking passage ( sequence of steps )
  • Deep tendon reflexes triggered heavy
  • Diminished sensitivity to pain
  • Disturbed temperature sensation
  • Difficulty chewing
  • Sensitive scalp
  • Some major initiating and maintaining sleep disturbance, daytime often very tired
  • Behavioral disorders, such as: hyperactivity, self- injurious behavior such as hitting the head against walls, etc., biting into his hands, picking at skin and scars, removal of the finger and toenails, insertion of foreign bodies in ears and nose, temper tantrums, destructive and aggressive behavior, irritability, self hug / pressing the hand with excitement.
  • Behavior, as observed, for example, in many people with autism (fear of contact, inability to speak, strong need for routine and uniformity in daily life)

( from: " What is Smith - Magenis Syndrome". . Raeburn JA et al The Smith - Magenis Syndrome Foundation, London 1999)

Diagnosis

The typical symptoms of Smith - Magenis syndrome are not sufficient for a reliable diagnosis. There are differential diagnostically relevant syndromes, which are quite similar to the SMS, such as Prader- Willi syndrome. A pure counting or looking at the chromosomes alone is also not sufficient to ensure the diagnosis. Therefore, genetic testing must be performed for a secured findings necessarily, referred to as fluorescence in situ hybridization ( FISH test ). Here, blood cells, which can be obtained as part of a normal blood sample, tested for the absence of certain sections of the chromosome 17. Because of the new studies on gene RAI1 the carriage of a specific probe for RAI1 seems mandatory. Further studies on this topic are but certainly necessary.

The small number of people with SMS can be explained well with the fact that the syndrome is often not diagnosed as such, and the children often different - get diagnosis, such as autism or a Aufmerksamkeits-Defizit/Hyperaktivitäts-Syndrom ( ADHD) - similar.

Treatment

Due to the genetic cause a cure is not possible, so that the therapy involves the treatment of the symptoms. May be helpful therapies such as physiotherapy, occupational therapy or speech therapy. A communication training with sign language or GuK may be helpful. Often people with the Smith - Magenis syndrome are life- long need of help and therapy.

There are several approaches to drug therapy available, however, the interventions will be limited here to mitigating the symptoms, not to a shutdown of the cause. Thus, the sleep problems in some people could be improved through the evening administration of melatonin, other medicines (such as Risperdal ) may be used to attenuate the self-injurious behavior.

History

It has been described scientifically in the early 1980s by the geneticist Ann Smith and Ellen Magenis and named after them.

Deletion (genetics) Intelligence quotient Prader–Willi syndrome
735127
de