Noonan's Syndrome

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Classification according to ICD-10
Q87.1 Congenital malformation syndromes that are predominantly associated with short stature
  • Noonan's Syndrome
ICD-10 online (WHO version 2019)

The Noonan syndrome is a genetic disease . The complex syndrome is characterized by a wide variety of genetic developmental disorders . The resulting malformations can affect the external appearance, but also internal organs . Congenital heart defects are typical. Since the identifiable symptoms are very similar to those of Ullrich-Turner syndrome , the Noonan syndrome is also referred to as "Pseudo-Turner syndrome" or "Male Turner syndrome". In contrast to Ullrich-Turner syndrome, however, no special features of the chromosomes (in terms of number and structure) can be detected.

The name "Noonan Syndrome" goes back to the American pediatric cardiologist Jacqueline Noonan , who first described the syndrome in 1963 and described it in detail in 1968.

causes

Half of people with Noonan syndrome have changes ( mutations ) in the PTPN-11 gene, which is on the long arm of chromosome 12 . This gene is responsible for a protein (SHP-2) that plays a central role in growth regulation and influences a large number of metabolic and growth processes. Many of these processes are regulated by activating the mitogen-activated protein kinase cascade ( MAP kinase pathway ). Other genes affected include the SOS1 and KRAS genes. Mutations in the protein kinase RAF1, which is at the upper end of the MAP kinase pathway, have now also been found in Noonan patients.

It is to be expected that further responsible genes in the MAP kinase pathway will be identified for the remaining cases.

Inheritance

Approx. 50% of the cases are sporadic, i. This means that parents of affected children are not themselves carriers of Noonan's syndrome. In other people, Noonan's syndrome is inherited , whereby the inheritance of the gene mutation is autosomal dominant ( autosomes = all chromosomes except the sex chromosomes ). This means that with one affected parent the probability of occurrence for children is 50% (both parents at 75%).

It is usually transmitted through the mother (3: 1), since males with Noonan syndrome are mostly sterile .

frequency

Noonan's syndrome is relatively common. Information about the frequency ranges from 1: 500 to 1: 2500. In Germany about 80,000 people are affected. The syndrome affects both sexes equally and is the second most common genetic cause after Down's syndrome (trisomy 21), which often leads to the occurrence of a heart defect .

Diagnosis and symptoms

The manifold forms that Noonan syndrome can assume make clinical diagnosis difficult. Many of the milder cases are likely to never be diagnosed.

The molecular genetic diagnosis of the PTPN-11 gene can now be used to confirm the suspected diagnosis. However, only about 50% have the mutation they are looking for. Above all, the analysis of the gene in the parents also allows a better assessment of the risk of subsequent pregnancies . A prenatal diagnosis is also possible if there is a specific suspicion in the context of prenatal diagnosis, e.g. B. possible by amniocentesis .

A cardio-facial-cutaneous syndrome , cherubism and Costello syndrome are to be distinguished .

Symptoms

12-year-old girl with Noonan syndrome and pronounced scoliosis

The misinformation on the affected gene triggers various symptoms and diseases . Not all characteristics appear in all children and are equally pronounced and with increasing age the symptoms become increasingly normal. That makes a clear diagnosis even more difficult.

As already mentioned, many symptoms are reminiscent of Ullrich-Turner syndrome . These primarily include short stature , which is less pronounced in Noonan's syndrome, the deep hairline on the neck , and occasionally the pterygium colli or "wing skin". This means a widened neck skin with a fold that pulls towards the shoulder .

The most common possible symptoms are briefly summarized below:

There is an association with juvenile myelomonocytic leukemia .

therapy

Only symptomatic therapy of Noonan syndrome is possible, e.g. B. Surgical correction of heart defects or the pterygium , wearing glasses or hearing aids , treatment of speech disorders through speech therapy or hormone therapy against short stature. There is currently no causal treatment for healing.

Learning difficulties and cognitive limitations

This article or the following section is not adequately provided with supporting documents ( e.g. individual evidence ). Information without sufficient evidence could be removed soon. Please help Wikipedia by researching the information and including good evidence.

While the majority of people with Noonan syndrome have an average IQ , just under 25% have a slight cognitive disability (IQ between 69 and 82): “The most common learning difficulty in children with Noonan syndrome is difficulty in verbal reasoning . No specific behavior pattern has been identified, although affected individuals often show signs of clumsiness, stubbornness and irritability . "

literature

  • G. Neuhäuser, H.-C. Steinhausen (Hrsg.): Intellectual disability - basics, clinical syndromes, treatment and rehabilitation. Stuttgart / Berlin / Cologne 1999, ISBN 3-17-013879-0 .
  • SA Yatsenko, M. del Valle Torrado, PH Fernandes, J. Wiszniewska, M. Gallego, J. Herrera, CA Bacino: Molecular characterization of a balanced rearrangement of chromosome 12 in two siblings with Noonan syndrome . In: American Journal of Medical Genetics Part A . 149A, no. December 12 , 2009, pp. 2723-2730 , doi : 10.1002 / ajmg.a.33112 , PMID 19938085 .
  • AA Romano, JE Allanson, J. Dahlgren, BD Gelb, B. Hall, ME Pierpont, AE Roberts, W. Robinson, CM Takemoto, JA Noonan: Noonan Syndrome: Clinical Features, Diagnosis, and Management Guidelines . In: Pediatrics . tape 126 , no. 4 , October 2010, p. 746-759 , doi : 10.1542 / peds.2009-3207 .

Web links

Individual evidence

  1. ↑ Jacqueline Anne Noonan, Dorothy A. Ehmke: Associated noncardiac malformations in children with congenital heart disease . Midwest Society for Pediatric Research Cincinnati, Ohio, Oct. 25 and 26, 1962. In: The Journal of Pediatrics . tape 63 , no. 3 , September 1963, p. 468-470 , doi : 10.1016 / S0022-3476 (63) 80441-2 .
  2. ↑ Jacqueline A. Noonan: Hypertelorism With Turner Phenotype . In: American Journal of Diseases of Children . tape 116 , no. 4 , October 1968, p. 373-380 , doi : 10.1001 / archpedi.1968.02100020377005 .
  3. ↑ G. Gillessen-Kaesbach, Y. Hellenbroich: Humangenetik . In: Pediatrics . Springer, Berlin / Heidelberg 2019, ISBN 978-3-662-57294-8 , pp. 3-22 , doi : 10.1007 / 978-3-662-57295-5_1 .
  4. ↑ Juvenile Myelomonocytic Leukemia. In: NORD (National Organization for Rare Disorders). Retrieved July 21, 2020 (English).
  5. ↑ Katharina Maidhof-Schmid, Ulrike Wößner, Jörg Klepper: Noonan syndrome - XX-Turner phenotype - Pseudo-Turner syndrome . Ed .: Noonan-Kinder e. V. Aschaffenburg May 2011 ( PDF ).