Microdeletion Syndrome 22q11

Classification according to ICD-10
Q93.5	Other deletions of a part of a chromosome
D82.1	DiGeorge syndrome
Q93.81	velocardiofacial syndrome
ICD-10 online (WHO version 2019)

The microdeletion syndrome 22q11 (MDS 22q11) belongs to the microdeletion syndromes and has various genetic disorders that are associated with changes on the long arm of chromosome 22 at position 11. This more common form of DiGeorge syndrome is abbreviated as DGS1. The microdeletion syndrome 10p13-14 (or MDS 10p13) with the abbreviation DGS2 is also described; here the short arm (= p) of chromosome 10 at position 13 is affected. In about 90% of the cases it is a new mutation ; in 10% of cases the syndrome becomes autosomal dominantinherited. Occasionally one also finds the names MDS 22q11.2 or MDS 22q11.21 with the 2 as an indication of the second sub-band on the long (= q) chromosome arm .

Epidemiology

Both sexes are equally affected. The incidence is given as one affected person per 2000 to 4000 live births . The syndrome is considered a rare disease . The mean life expectancy is significantly reduced with severe complications. Most patients die in early childhood ; only a few survive into adulthood . Half of the children of those affected are also affected.

Designations

These include, among others, the DiGeorge syndrome (also velocardiofacial syndrome or congenital thymus aplasia ) and the Shprintzen syndrome , which, due to their different forms, show flowing transitions into one another. Important features are a heart defect , a soft palate or a cleft palate , mild features of the facial features, in newborns possibly a tendency to infection due to insufficient development of the thymus and a decreased calcium concentration in the blood due to insufficient development of the parathyroid glands . Partial defects are more common than total thymic aplasia.

The American acronym "CATCH-22-Syndrome", which was previously proposed for the microdeletion syndrome 22q11, based on a successful novel by Joseph Heller , is generally no longer used because its content is inappropriate. CATCH = Cardiac abnormality, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia + Hypoparathyroidism = Cardiac abnormality, facial abnormality, thymus aplasia , cleft palate, hypocalcemia and primary hypoparathyroidism .

Böttiger and Wonstedt were the first to describe it in 1927. It was named after the American pediatrician and endocrinologist Angelo Mario DiGeorge (born April 15, 1921 in Philadelphia , † October 11, 2009 in East Falls in Philadelphia). The disease was formerly known as Sedlackova syndrome, as pharyngeal pouch syndrome and a syndrome of the third and fourth pharyngeal pouch called. In English , the DiGeorge syndrome is also called Cayler cardiofacial syndrome or CTAF ( conotruncal anomaly face syndrome ). The Shprintzen syndrome is named after the speech Robert J. Shprintzen named Service.

Symptoms

Because of microdeletions on the long arm of chromosome 22 (22q11) already occurs during pregnancy in the child developmental disorders (defective development of the 3rd and 4th pharyngeal pouch ). These can vary in severity to heart defects (e.g. ventricular septal defect ), malformations of the vessels (e.g. in the area of ​​the aortic arch , such as aortic hypoplasia ), failure of the parathyroid glands (hypoparathyroidism), lack of development or formation of only a small thymus ( Thymus aplasia or thymus hypoplasia ) and lead to facial malformations (e.g. microgenius , cleft lip and palate or micrognathia ).

Renal involvement (kidney dysplasia up to renal agenesis ) also occurs in about a third of those affected . These congenital malformations of the kidneys and the lower urinary tract are summarized under the English acronym CAKUT (= congenital anomalies of the kidney and urinary tract).

The symptoms are determined by the different strengths of the individual characteristics. Facial malformations such as As a cleft lip and palate are often already under prenatal diagnosis in ultrasound striking. Facial malformations that continue to occur are: comparatively broad nasal root, long nasal bridge, wide nose tip, widely spaced eyes ( hypertelorism ), antimongoloid eyelid axis , strabismus , epicanthus , short philtrum and auricular dysplasia.

Serious heart defects and vascular malformations, if not already prenatal, are usually discovered some time after birth through the typical symptoms and an ultrasound examination of the heart ( echocardiography ). Typically occurring heart defects are primarily aortic arch anomalies, but also a common arterial trunk , a Fallot tetralogy or a ventricular septal defect .

The thymic hypoplasia may be due to the lack of formation of T-lymphocytes (isolated T cell deficiency ) to serious infections of the child and generally lead to an increased susceptibility to infection (see immunodeficiency ). If there is sufficient residual function of the thymus, there is often no increased susceptibility to infection to be observed. Because of the T-cell defect, vaccinations with live attenuated pathogens are prohibited. Life - threatening complications in the context of a graft-versus-host reaction in blood transfusions can be reduced by prior radioactive irradiation of the blood products .

The lack or deficiency of parathyroid hormone , which is formed in the parathyroid gland, can lead to seizures ( tetany ) due to the resulting calcium deficiency (see also hypoparathyroidism ).

It also comes to developmental delays to a reduced muscle tone , frequent respiratory infections, hearing loss , to increased constipation , to mental retardation to learning disabilities to mental changes to behavioral problems , to reactive depression and significantly more likely to schizophrenia or other psychosis .

Since microdeletion syndrome 22q11 is a collective term for various deletions, not all symptoms have to occur in every case, and they can be of different severity.

diagnosis

A suspected diagnosis can be made through the combined occurrence of typical malformations. Certain congenital malformations of the heart are often the first clue. The suspicion can be confirmed by molecular cytogenetic diagnostics and detection of the 22q11 deletion in the context of human genetics . Fluorescence in situ hybridization ( FISH test ) is the method of choice here. A 22q11 deletion can be familial, so the parents of an affected child should also be examined if they so wish, as the risk of recurrence for further pregnancies can be weighed in this way.

Differential diagnoses

Not to be confused with the microdeletion syndrome 22q11 (Shprintzen syndrome) is Shprintzen-Goldberg syndrome , a Marfan syndrome- like craniosynostosis syndrome. The spectrum also includes the possibly independent Kousseff syndrome . The Takao syndrome , the floating harbor syndrome , the Alagille syndrome , the Smith-Lemli-Opitz syndrome and the VACTERL association (also known as the VATER syndrome) are to be distinguished. Pinski-DiGeorge-Harley-Baird syndrome (or Pinski-George-Harley-Baird syndrome or, more correctly, Pinsky-DiGeorge-Harley-Baird syndrome) must also be distinguished as a complex oculocerebral malformation syndrome . The Pinski-DiGeorge-Harley syndrome (which is identical to it?) Is a microphthalmia with mental retardation . It is not to be confused with oculo-cerebro-renal syndrome ( Lowe's syndrome ).

therapy

Due to the genetic cause, a causal cure is not possible. However, a multidisciplinary symptomatic therapy depending on the severity is indicated, in particular the surgical correction of the malformations that occur and the therapy of the concomitant diseases . This includes facial corrections, surgical correction of heart defects and kidney abnormalities, an oral calcium substitution, vitamin D3 substitution with cholecalciferol and any transplantation of bone marrow and fetal thymus tissue.

As innovation since 2017, the daily applies subcutaneous injection of the nature-identical recombinant parathyroid hormone with the trade name Natpar ( portmanteau word :; frequent natural parathyroid hormone misspelling Naptár ) in terms of hormone replacement therapy . Natpar is considered an orphan drug from Shire plc with daily therapy costs of almost 250 euros regardless of the dose (DDD = Defined Daily Dose ). It is cheaper to treat a tetany, for example with "AT 10 pearls" (AT = anti-tetany, dihydrotachysterol ) with daily therapy costs of less than € 1 in a low dose. Calcidiol and calcitriol are available as drugs. There used to be attempts at therapy with thymosin .

Infections are treated with an antibiotic , a virostat or an antifungal agent .

Self-help groups and relatives groups as well as neurological and psychotherapeutic treatment are recommended . If necessary, speech therapy is indicated.

literature

• Christian P. Speer, Manfred Gahr: Pediatrics. Springer-Verlag, Berlin et al. 2001, ISBN 3-540-67333-4 .
• Berthold Koletzko (Ed.): Paediatrics and Adolescent Medicine , 12th edition, Springer, Berlin 2004, ISBN 3-540-44365-7 .
• Willibald Pschyrembel: Clinical Dictionary , 267th edition, de Gruyter , Berlin, Boston 2017, ISBN 978-3-11-049497-6 , p. 1155 (keyword: microdeletion ).

Web links

Microdeletion Syndrome 22q11.  In: Online Mendelian Inheritance in Man . (English)

Individual evidence

1. ^ Maxim Zetkin , Herbert Schaldach: Lexikon der Medizin , 16th edition, Ullstein Medical , Wiesbaden 1999, ISBN 3-86126-126-X , p. 438 f.
2. ↑ RD Burnside: 22q11.21 Deletion syndromes: a review of proximal, central, and distal deletions and their associated features , Cytogenetic and Genome Research , 2015; 146, pp. 89-99.
3. ↑ Harrison's Internal Medicine , 19th edition, Volume 3, Thieme-Verlag , Berlin 2016, ISBN 978-3-88624-560-4 , p. 3042 f.
4. ↑ Peter Reuter: Springer Clinical Dictionary , 1st edition, Springer-Verlag, Heidelberg 2007, ISBN 978-3-540-34601-2 , p. 423.
5. ↑ Other information: 75 percent. Source: Gerd Herold et alii: Internal Medicine 2020 , self-published , Cologne 2019, ISBN 978-3-9814660-9-6 , p. 71.
6. ^ The Merck Manual , 20th Edition, Kenilworth (New Jersey) 2018, ISBN 978-0-911910-42-1 , p. 2492.
7. ^ Harrison's internal medicine , 19th edition, volume 3, Thieme-Verlag , Berlin 2016, ISBN 978-3-88624-560-4 , p. 3042.
8. ↑ Latin : velum palatinum = soft palate; cardia = heart ; facies = face .
9. ^ LJ Kobrynski, KE Sullivan: Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes , in: The Lancet 2007; 370, pp. 1443-1452.
10. ^ Robert J. Shprintzen , Anne Marie Higgins, Kevin Antshel, Wanda Fremont, Nancy Roizen, Wendy Kates: “Velo-cardio-facial syndrome”, Current Opinion in Pediatrics , Volume 17, 2005, pp. 725–730.
11. ^ A comment on another paper , M. Cooper, R. Peterson, R. Good (1965): "A new concept of the cellular basis of immunity". The Journal of Pediatrics . 67 (5): 907. doi: 10.1016 / S0022-3476 (65) 81796-6 .
12. ↑ Angelo Mario DiGeorge : Congenital absence of the thymus and its immunologic consequences: concurrence with congenital hypoparathyroidism . IV (1). White Plains , New York: March of Dimes - Birth Defects Foundation; 1968, pp. 116-121.
13. ↑ Peter Reuter: Springer Clinical Dictionary , 1st edition, Springer-Verlag, Heidelberg 2007, ISBN 978-3-540-34601-2 , p. 423.
14. ↑ In the English-speaking countries, in embryonic heart development, the upper section of the bulb cordis is called the conotruncus (in Germany: conus cordis ).
15. ↑ DocCheck Flexikon: Keyword Bulbus cordis .
16. ↑ Walter Siegenthaler : Differentialdiagnose inner Kranken , 15th edition, Georg Thieme Verlag , Stuttgart, New York 1984, ISBN 3-13-344815-3 , p. 6.61.
17. ↑ Angelo Restivo, Anna Sarkozy, Maria Cristina Digilio, Bruno Dallapiccola, Bruno Marino (February 2006): 22q11 Deletion syndrome: a review of some developmental biology aspects of the cardiovascular system . Journal of Cardiovascular Medicine 7 (2), pp. 77-85. PMID 16645366 . doi: 10.2459 / 01.JCM.0000203848.90267.3e .
18. ↑ Jörg Dötsch, Lutz T. Weber (Ed.): Kidney Diseases in Childhood and Adolescence , Springer-Verlag, Berlin 2017, ISBN 978-3-662-48788-4 , p. 157.
19. ↑ L. Pinsky, Angelo Mario DiGeorge , RD Harley, HW Baird: Microphthalmos, Corneal Opacity, Mental Retardation, and Spastic Cerebral Palsy: an Oculocerebral Syndrome, in: The Journal of Pediatrics , 67th year, September 1965, p. 387– 398; doi: 10.1016 / s0022-3476 (65) 80399-7 .
20. ^ Günter Thiele (ed.): Handlexikon der Medizin, Volume 3 (L – R), Urban & Schwarzenberg , Munich, Vienna, Baltimore without year, p. 1912.
21. ↑ Rote Liste 2019, 59th edition, Frankfurt am Main 2018, ISBN 978-3-946057-42-0 , p. 1016, number 68 028: two cartridges for 28 days cost € 6968.26.
22. ↑ Dieter Palitzsch: Pädiatrie , Ferdinand Enke Verlag , Stuttgart 1983, ISBN 3-432-93131-X , p. 261.

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 !