Cat's Eye Syndrome

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The typical, congenital vertical-oval cleft formation on the iris

The cat's eye syndrome (synonym: Schmid-Fraccaro syndrome and coloboma anal atresia syndrome ) is a rare hereditary disease in humans, the main symptoms of which are changes in the eyes ( coloboma ) and a malformation of the rectum ( anal atresia ).

The severity of the symptoms does not depend on the severity of the genetic damage. In classic cases , the analysis of the genetic material reveals an excess chromosome , which consists of a fragment of chromosome 22 . Names refer to occurring in almost all cases vertically oval gap formation (coloboma) on the iris ( Iris ) attached to the slit pupils of cat reminds eye.

Epidemiology

The cat's eye syndrome is a congenital disease that is caused by a change in the genetic make-up . The inheritance is autosomal - dominant . The incidence of cat's eye syndrome is 1.35 cases per 100,000 people. As of 2009, 105 cases had been published.

root cause

The classic cause of this syndrome is an abnormality in chromosome 22 ( region q11.2). In 83% of cases, a small extra chromosome that can be found in all cells of the body is characteristic, in which part of the genetic information of chromosome 22 is found. It is believed that this by inversion - duplication arises is therefore bicentric and carries at both ends satellites. Since the genetic information of the affected region is more than duplicated in the patient's genetic makeup , one speaks of a tri- or tetrasomy .

However, an extra chromosome cannot be detected in all cases. An (unrecognized) mosaic , a gene mutation or an unrecognized translocation are then discussed as the cause .

Clinical appearance

X-ray of anal atresia.
It can be seen that the large intestine ends blindly, i.e. the anus is missing.

The recognizable physical effects ( phenotype ) of the genetic defects are not the same for all affected persons. The congenital vertical-oval gap formation on the iris, which is responsible for the name cat's eye syndrome, is also not present in all of the cases described.

Typical symptoms are anal atresia and other anorectal malformations, unilateral and bilateral iris colobomas and preauricular appendages - lobule-like appendages, usually made of skin - or connective tissue close to the auricle . The eyelid axes of those affected often run obliquely outwards and downwards ( laterocaudal ). Often the phenotypic changes are accompanied by a mostly minor intellectual disability .

Malformations of the urinary and reproductive system , such as double ureters , water sac kidney and displacement of the urethral orifice, are rarer .

The skeletal system can also be affected, including short stature , missing thumb , deformation of the ribs , sirenomelia and spina bifida .

There are also a number of symptoms observed in the eyes , for example long eye relief , strabismus , Mongolian fold , cataracts , retinal dysplasia and pathological reduction in the size of the eyeball .

Also, heart failure such as tetralogy of Fallot or isolated septal defects of atrial and chamber , as well as the involvement of other organs such as the brain ( oligophrenia ), biliary ( atresia of the gallbladder ) and colon ( Hirschsprung's disease ) are described.

Diagnosis and differential diagnosis

Classification according to ICD-10
Q92.8 Other specified trisomies and partial trisomies of the autosomes
Q13.0 Congenital malformations of the anterior segment of the eye - iris coloboma
Q42.- Congenital absence, atresia and stenosis of the large intestine
ICD-10 online (WHO version 2019)

diagnosis

If the typical main symptoms (coloboma and anal atresia) are present, the diagnosis of cat's eye syndrome can be made clinically - i.e. without analyzing the genetic material.

The diagnosis of the type and extent of the genetic defect in individual cases is carried out by means of chromosome analysis . The most reliable criterion for diagnosis is the presence of the extra chromosome.

If a genetic analysis is carried out in one case and a corresponding tri- or tetrasomy 22 is found, then the term is also used in the absence of the typical main symptoms, but one speaks of an “incomplete” cat's eye syndrome. Conversely, this diagnosis can be made in patients with typical clinical signs but without verifiable genetic changes, especially if the thumbs are noticeably long and the hands and feet are in a position that deviates from the norm.

Differential diagnosis

Congenital disorders, which are usually associated with a lack of talent and malformations, are caused by mutations in larger genome sections and thus lead to a dose effect of numerous genes, are also called genomic diseases . Mutations that encompass several megabase pairs can often be characterized cytogenetically , since whole chromosome bands are changed by such an event . Such disturbances are by no means rare occurrences. They make up about 1% of all congenital disorders. The most common disorder of this type is DiGeorge syndrome (syn .: Velocardiofaciales syndrome), which is caused by a mutation in the area of ​​chromosome band 22q11, similar to the cat's eye syndrome.

The DiGeorge syndrome and the conotruncal anomaly face syndrome , together with the very rare (22) syndrome and the cat's eye syndrome, represent a cluster of disorders that is described by the term “genomic disorders in the range of 22q11”. These three congenital diseases are the ones most commonly associated with changes in the area of ​​chromosome 22q11.

Schizophrenia and bipolar disorders are also indirectly associated with changes in 22q11, since this is where the gene for the enzyme catechol-O-methyltransferase is located and patients with a 22q11 deletion and DiGeorge syndrome have psychosis in about 30% of cases develop. A similar situation as in the case of DiGeorge syndrome (congenital disorder with haploinsufficiency and psychosis) can also be found in Williams-Beuren syndrome . A syndrome of microduplications and microtriplications of a 22q11.2 region appears to be a separate syndrome. Other disorders associated with this region are the autosomal dominant "giant platelet syndrome", Fechtner syndrome and rhabdoid predisposition syndrome .

Due to the variety of disorders described, only the presumed mechanism of Cat's Eye, DiGeorge and (22) syndrome will be briefly described at this point. In all three diseases there is a maldistribution of the region 22q11. In DiGeorge syndrome there is a so-called haploinsufficiency of the affected genes. There is only one healthy allele from region 22q11 . More precisely, there is a deletion of the segment of 22q11 facing the telomere . In the (22) syndrome, the affected individuals have an additional copy of the region of 22q11 facing the centromere . In cat-eye syndrome, two additional copies of the centromeric segment of 22q11 are regularly found. These extra copies are usually in the form of an extra bicentric chromosome . There are three different variants of this additional chromosome. An analysis of the genes in this region indicated that the dose effect affects around 24 genes in DiGeorge syndrome and around 14 genes in cat's eye syndrome.

Prognosis and therapy

The prognosis of the cat's eye syndrome depends largely on the severity and type of malformations of the heart and kidneys as well as the extent of the mental development disorder. Life expectancy is not restricted in patients with few or mild symptoms .

Family counseling after chromosome analysis is recommended as a preventive measure. A distinction must be made between cases with evidence of an extra chromosome and those without evidence. The siblings of the former are not considered to be at risk of passing on the disease , provided they do not have an extra chromosome and no further cases (even with more distant blood relatives ) are known. In all other cases there is a potentially increased risk of this.

Anal atresia and malformations of the heart and kidneys , if any, are of central interest in therapy . Anal atresia is corrected surgically as it would lead to rapid death of the newborn. The treatment of malformations of the heart and kidneys depends on their type. Incorrectable errors can significantly reduce life expectancy.

History and origin of the name

The name cat-eye syndrome refers to the congenital vertical-oval fissures on the iris, which are particularly typical for this disease pattern and present in almost all cases, which give the eyes of those affected a "cat-like" appearance.

An independent syndrome consisting of iris coloboma and anal atresia was first described by Otto Haab in 1878 (hence the name coloboma-anal atresia syndrome ), but it was not defined as an independent disease until 1969. At this point in time, however, the possible presence of an extra chromosome was already known; the first description of an extra chromosome that appeared in a patient with coloboma and anal atresia was published in 1965. Werner Schmid ( Zurich ) and Marco Fraccaro ( Pavia ) were instrumental in this discovery (hence the name Schmid-Fraccaro syndrome ). In 1972, Erica Bühler and co-workers first recognized that the extra chromosome originates from chromosome 22 and that it is at least a partial trisomy 22 .

Web links

literature

  • J. Kunze: Atlas of the clinical syndromes: for clinic and practice. Schattauer Verlag, 2009, ISBN 978-3-7945-2657-4 , pp. 94-95.
  • H. Chen: Atlas of Genetic Diagnosis and Counseling. Humana Press, 2006, ISBN 1-58829-681-4 , pp. 136-138.
  • AJ Augustin: Ophthalmology. Springer, 2007, ISBN 978-3-540-30454-8 , p. 493.

Individual evidence

  1. ↑ a b c Orphanet: Cat Eye Syndrome
  2. ↑ Orphanet Report Series: Rare Diseases - Data Collection. Edition August 2008, p. 6 (PDF) ( Memento from November 18, 2008 in the Internet Archive )
  3. ↑ Report on the ECRD2005 conference, p. 21 (PDF)
  4. ↑ a b c d e f J. Kunze: Atlas of the clinical syndromes: For clinic and practice. Schattauer Verlag, 2009, ISBN 978-3-7945-2657-4 , pp. 94–95 ( limited preview in Google book search).
  5. ↑ a b c d e f R. Witkowski et al: Lexicon of syndromes and malformations: causes, genetics, risks. Springer, 2003, ISBN 3-540-44305-3 , p. 664ff ( limited preview in the Google book search).
  6. ↑ a b A. Wischermann et al .: Partial polysomy 22 without cat eye. In: Monthly Pediatrics. 144, No. 9, 1996, ISSN  0026-9298 , pp. 924-926, doi: 10.1007 / s001120050061 .
  7. ↑ Wolfgang Hammerstein, Walter Lisch: Ophthalmologische Genetik. Enke Verlag, Stuttgart, 1985, ISBN 3-432-94941-3 , p. 168.
  8. ↑ a b c A. J. Augustin: Ophthalmology. Springer, 2007, ISBN 978-3-540-30454-8 , p. 493 ( limited preview in the Google book search).
  9. ↑ Wolfgang Hammerstein, Walter Lisch: Ophthalmologische Genetik. Enke Verlag, Stuttgart 1985, ISBN 3-432-94941-3 , p. 40.
  10. ↑ M. Lerone et al: The Genetics of Anorectal Malformations: A complex matter. In: Semin Pediatr Surg 1997, 6, pp. 170-179.
  11. ↑ Alphabetical directory for the ICD-10-WHO Version 2019, Volume 3. German Institute for Medical Documentation and Information (DIMDI), Cologne, 2019, p. 443
  12. ↑ J. Kunze et al.: Cat Eye Syndrome. In: Human Genetics. 144, No. 9, 1975, ISSN  0340-6717 , pp. 271-289, doi: 10.1007 / BF00285379 .
  13. ↑ a b G. Lüleci et al: A hereditary bisatellite-dicentric supernumerary chromosome in a case of cat-eye syndrome. In: Hereditas, 111/1/1989, pp. 7-10, doi: 10.1111 / j.1601-5223.1989.tb00369.x .
  14. ↑ H. Chen: Atlas of genetic diagnosis and counseling. Humana Press, 2006, ISBN 1-58829-681-4 , pp. 136-138 ( limited preview in Google book search); Note: A picture of the typical extra chromosome as part of a chromosome analysis can be found on page 138 at the bottom right
  15. ↑ H. Yamagishi: The 22q11.2 deletion syndrome. In: Keio J Med. 51, 2002, pp. 77-88. PMID 12125909 (Review)
  16. ↑ HH McDermid, BE Morrow: Genomic disorders on 22q11. In: Am J Hum Genet. 70, 2002, pp. 1077-1088. PMID 11925570 (Review)
  17. ^ N. Craddock et al .: The genetics of schizophrenia and bipolar disorder: dissecting psychosis. In: J Med Genet 42, 2005, pp. 193-204. PMID 15744031
  18. ↑ D. Ivanov et al .: Chromosome 22q11 deletions, velo-cardio-facial syndrome and early-onset psychosis. Molecular genetic study. In: Br J Psychiatry. 183, 2003, pp. 409-413. PMID 14594915
  19. ↑ M. Tassabehji: Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. In: Hum Mol Genet 12, 2003, pp. R229-237. PMID 12952863 (Review)
  20. ↑ TM Yobb include: Microduplication and triplication of 22q11.2: a highly variable syndrome. In: Am J Hum Genet. 76, 2005, pp. 865-876. PMID 15800846
  21. ↑ A. Toren et al .: Autosomal-dominant giant platelet syndromes: a hint of the same genetic defect as in Fechtner syndrome owing to a similar genetic linkage to chromosome 22q11-13. In: Blood 96, 2000, pp. 3447-3451. PMID 11071640 .
  22. ↑ A. Toren et al .: Genetic linkage of autosomal-dominant Alport syndrome with leukocyte inclusions and macrothrombocytopenia (Fechtner syndrome) to chromosome 22q11-13. In: Am J Hum Genet. 65, 1999, pp. 1711-1717. PMID 10577925
  23. ^ HE McDermid, BE Morrow: Genomic disorders on 22q11. In: Am J Hum Genet. 70, 2002, pp. 1077-1088. PMID 11925570 (Review)
  24. ↑ C. Thomas, J. Cordier, S. Gilgenkrantz, A. Reny, A. Raspiller: An unusual syndrome: colobomatous disorder of the eyeball, anal atresia, multiple congenital anomalies and presence of an extra chromosome. In: Annales D'oculistique. 202, No. 10, 1969, pp. 1021-1031, PMID 4983376 .
  25. ^ A b G. Schachenmann, W. Schmid, M. Fraccaro, A. Mannini, L. Tiepolo, GP Perona, E. Sartori: Chromosomes in coloboma and anal atresia. In: Lancet. 2, No. 7406, 1965, p. 290, PMID 14330081 ; quoted in: H. Chen: Atlas of genetic diagnosis and counseling. Humana Press, 2006, ISBN 1-58829-681-4 , pp. 136-137 ( limited preview in Google book search).
  26. ↑ Erica M. Bühler, Károly Méhes, Hansjakob Müller, Gerhard R. Stalder: Cat-eye syndrome, a partial trisomy 22. In: Human Genetics. 15, No. 2, 1972, pp. 150-162, doi: 10.1007 / BF00295742 , PMID 5049068 ; quoted from: Güven Lüleci, Gülseren Bagci, Mürüvet Kivran, Ersin Lüleci, Sirri Bektaş, Seher Başaran: A hereditary bisatellite-dicentric supernumerary chromosome in a case of cat-eye syndrome. In: Hereditas. 111, No. 1, 1989, pp. 7-10, doi: 10.1111 / j.1601-5223.1989.tb00369.x .
This article was added to the list of excellent articles on February 24, 2010 in this version .