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Partial Trisomy 21

Partial Trisomy 21 Down's

Partial trisomy 21 (PT21) is a type of trisomy 21 where only a part of chromosome 21 is present in three copies. Individuals with PT21 may exhibit a smaller number of Down's syndrome (DS) characteristics. The existence of PT21 is helpful in identifying the gene loci responsible for the Down's syndrome phenotypes.


Presentation

Partial trisomy 21 is a rare clinical entity. It is characterized by the presence of only a part of chromosome 21 as an extra copy. Usually, through non-disjunction during meiosis or mitosis, there are three complete copies of chromosome 21. In the case of mosaicism, some of the cells of the body express the trisomy. PT21 has been used in Down's syndrome research, to try and locate the genes responsible for the typical Down's syndrome phenotype, with the discovery of regions such as the Down syndrome critical region (DSCR) [1]. PT21 shows a heterogeneous expression of phenotypes, as well as genetic variation.

Studies have shown that several genes on chromosome 21 are able to code for abnormalities expressed, such as cognitive impairment [2] [3]. Furthermore, it has been shown that the DSCR region is not solely responsible for the phenotypes observed, but may have an input in their expression [2] [3].

Typically, children with PT21 exhibit fewer features of DS or none at all. Some cases only experience mental impairment [4].

DS is the most frequently reported birth defect, with the incidence increasing with maternal age [5]. The typical features of the condition include intellectual impairment, hypotonia during the neonatal period, flat profile, flattening of the nasal bridge and occiput, epicanthal folds, upward slanted eyes, microcephaly, macroglossia with lack of a central fissure, and small ears. Brushfield spots may be observed in the iris.

In addition, children with DS may have a single palmar crease, short hands and fingers, clinodactyly, sandal gap deformity, and plantar furrow. Growth delay, short stature, decreased intelligence quotient (IQ) may be detected during development, as well as traits of depression, autism, and attention deficit hyperactivity disorder may be seen.

Systemic effects of DS include a higher incidence of duodenal atresia, duodenal stenosis, intestinal obstruction, leukemia, Hirschsprung's disease, Alzheimer's disease, and congenital heart diseases such as ventricular septal defect and atrioventricular canal defect.

Down Syndrome
  • PT21 has been used in Down's syndrome research, to try and locate the genes responsible for the typical Down's syndrome phenotype, with the discovery of regions such as the Down syndrome critical region (DSCR).[symptoma.com]
  • The phenotype of the patient was not typical for Down's syndrome, providing additional evidence that trisomy of band 21q22 is pathogenetic for the phenotype of Down's syndrome.[ncbi.nlm.nih.gov]
  • KEYWORDS: APP; Array comparative genome hybridization (aCGH); Chromosome 21; DNAJB6; DSCR1; DYRK1; DYRK1A; DnaJ/HSP40 homolog subfamily B member 6; Down syndrome; Down syndrome critical region gene 1; MX1; NCAPG2; OMIM; Online Mendelian Inheritance in[ncbi.nlm.nih.gov]
  • Despite trisomy for a substantial portion of chromosome 21, the patient showed only minor stigmata compatible with Down syndrome.[ncbi.nlm.nih.gov]
  • Last updated Sept. 13, 2017 The topic Partial Trisomy 21 Down Syndrome you are seeking is a synonym, or alternative name, or is closely related to the medical condition Down Syndrome . Quick Summary: Down syndrome is the trisomy of chromosome 21.[dovemed.com]
Multiple Congenital Anomalies
  • Abstract A patient with a double partial trisomy 20 and 21 with mild mental retardation and multiple congenital anomalies is presented.[ncbi.nlm.nih.gov]
Intestinal Atresia
  • There was no history of intestinal atresia or other gastrointestinal malformations. Thyroid studies were normal, as was her tone, with no abnormal joint laxity or herniae.[nature.com]
Heart Murmur
  • Many phenotypic features of DS were present including hypotonia, flat occiput, flat facies, up-slanted palpebral fissures, epicanthic folds, flat nasal bridge, macroglossia, open mouth, small ears and a heart murmur.[ncbi.nlm.nih.gov]
Receding Chin
  • Abstract A female patient with mild mental retardation with spatial perceptual difficulties, microcephaly, depressed nasal root, receding chin, webbed neck, low hairline, shield chest, cubitus valgus, scoliosis and dermatoglyphic findings not characteristic[ncbi.nlm.nih.gov]
Prominent Cheeks
  • The proband postnatally displayed by dysmorphic features of a round flat face with prominent cheeks and high forehead, upward slanting palpebral fissures, epicanthic folds, hypertelorism, a short nose, a broad and depressed nasal bridge, anteverted nares[ncbi.nlm.nih.gov]
Suggestibility
  • Results from phenotypic, chromosome banding and superoxide dismutase (SOD) gene dosage studies suggest a karyotype of 46,XX,-12, t(12pter to 12qter::21q21 to 21q22.?2).[ncbi.nlm.nih.gov]
  • We suggest a DS CHD candidate region on 21q22.2 (0.96Mb), being shared by most PT21 cases with CHD and containing three known protein-coding genes (DSCAM, BACE2, PLAC4) and four known non-coding RNAs (DSCAM-AS1, DSCAM-IT1, LINC00323, MIR3197).[ncbi.nlm.nih.gov]
  • In particular, the face and the presence of hypotonia and keratoconus were suggestive for the DS although the condition remained unnoticed until his adult age array comparative genomic hybridization (aCGH) revealed a 10.1 Mb duplication in 21q22.13q22.3[ncbi.nlm.nih.gov]
  • Postnatal clinical evaluation The patient was referred to Medical Genetics at 4 years of age with physical features suggestive of DS.[nature.com]
  • It has been suggested that advanced maternal age can pose a greater risk for bearing a child with Trisomy 21. For a woman that is under the age of 35 the chances of having a child with Trisomy 21 are 1 in 1ooo.[ucdreprosurvey.wordpress.com]

Workup

Prenatal diagnosis of Down's syndrome, and hence some cases of partial trisomy 21, can be achieved through amniocentesis or chorionic villus sampling [6]. Abnormal features can be distinguished in a fetus, through ultrasound, usually between 14 and 24 weeks gestation [7]. These include flattened nasal bridge, thickened nuchal fold and dilated ventricles. The prenatal screening is extremely effective in detecting DS [8].

Prenatal biochemical markers include abnormally high levels of alpha-fetoprotein, inhibin, estriol, and beta HCG (human chorionic gonadotropin), which are tested in the first and second trimesters. Fetal DNA present in maternal blood can also be tested for trisomy 21 and PT21 in noninvasive prenatal screening (NIPS).

After birth, features of DS may be present, and additional chromosome or karyotype analysis will reveal PT21 [9]. A correlation of the clinical characteristics of DS is needed in order to make a clinical diagnosis.

Treatment

  • […] wide array of specialties-including neurology, cardiology, hematology, nephrology, genetics, endocrinology, oncology, dermatology, and psychiatry-revealing the underlying molecular mechanisms of disease, as well as novel routes to the unprecedented treatments[books.google.com]
  • […] means that the individual has 3 copies of chromosome 21 in some, but not every cell of the body Please find comprehensive information on Down Syndrome regarding definition, distribution, risk factors, causes, signs & symptoms, diagnosis, complications, treatment[dovemed.com]
  • The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.[orpha.net]
  • Adolescents or teens with developmental delays live in community-based group homes at our treatment center that provide a normal living environment and increase chances for success.[ascentchs.com]
  • New treatment prospects The application of novel molecular techniques on one of the genes in this presumed critical region is starting to open up interesting prospects for treatment of the syndrome at the gene level.[bbvaopenmind.com]

Prognosis

  • […] has 3 copies of chromosome 21 in some, but not every cell of the body Please find comprehensive information on Down Syndrome regarding definition, distribution, risk factors, causes, signs & symptoms, diagnosis, complications, treatment, prevention, prognosis[dovemed.com]
  • PROGNOSIS life expectancy, formerly poor, has greatly increased, due to antibiotherapy and surgery. prognosis can be impaired by: 1 - the extreme susceptibility to infections. 2 - malformations, cardiac malformations in particular. 3 - acute leukemia[atlasgeneticsoncology.org]
  • Prognosis Median life expectancy is now above the age of 55 years. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • […] cataracts Seizures (5-10%) Correlation between age and prevalence Peaks at infancy and 4th-5th decade of life Short stature (average at 3rd percentile) Obesity Wide gap between first and second toes Hypotonia Clinodactyly of the 5th fingers Natural History/Prognosis[en.wikibooks.org]
  • We called in a clergyperson for one case who candidly said he’d end the pregnancy, so bleak was the prognosis.[blogs.plos.org]

Etiology

  • Etiology In 95% of the cases, trisomy 21 is free'': the extra chromosome is due to an accidental non-disjunction during meiosis. 2-3% of those cases are in a mosaic state.[orpha.net]
  • : nondisjunction in meiosis; craniofacial, ocular and cerebral malformations, limb and cardiovascular anomalies, defects of heart, diaphragm and kidneys Edwards Syndrome-most die within a year; etiology: nondisjunction in meiosis; low birth weight, multiple[quizlet.com]
  • Jump to navigation Jump to search Down Syndrome - Trisomy 21 Genetics [ edit ] 3 possible etiologies: Full trisomy 21 (95% of the cases) Due to nondisjunction during meiosis Usually maternal nondisjunction (90-95% of these cases) 75% of maternal nondisjunction[en.wikibooks.org]
  • Down syndrome was described in 1861 by Seguin in 1866 by Langdon-Down who specify the clinical features of this syndrome and in 1959, Lejeune specifies the chromosomal etiology.[doctortipster.com]
  • In Etiology and Pathogenesis of Down Syndrome, Wiley-Liss, 1995, p 43-55. Hernandez D and Fisher EMC. Down syndrome genetics: unravelling a multifactorial disorder. Hum. mol. Genet., 5: 1411-1416, 1996. Shapiro, BL.[ds-health.com]

Epidemiology

  • EPIDEMIOLOGY (a question on epidemiology would also include recurrence risks according to the karyotypic findings: see paragraph on the karyotype). 1,5 /1 000 births. Sex ratio: 3 males/2 females. Increased median maternal age (34 years).[atlasgeneticsoncology.org]
  • Epidemiology Incidence Down's syndrome is one of the most common genetic disorders, affecting 1 in 650-1,000 [ 5 ]. The underlying genetic defect is trisomy 21 in 94% of cases.[patient.info]
Sex distribution
Age distribution

Pathophysiology

  • Within the framework of clinical internal medicine, they will gain critical knowledge of the many powerful molecular biology-based developments now so rapidly enhancing our understanding of the pathophysiology of disease, improving the feasibility and[books.google.com]

Prevention

  • […] individual has 3 copies of chromosome 21 in some, but not every cell of the body Please find comprehensive information on Down Syndrome regarding definition, distribution, risk factors, causes, signs & symptoms, diagnosis, complications, treatment, prevention[dovemed.com]
  • These are made up of a protein called tau that builds up inside of neurons in the brain and prevents them from functioning properly.[theconversation.com]
  • Accounting for nearly 20% of all infant deaths, birth defects are the leading cause of infant mortality, according to the Centers for Disease Control And Prevention . Three of the most common newborn aneuplodies are trisomies 13, 18, and 21.[blog.geneticslab.emory.edu]
  • If Your Baby Has Trisomy 22 If you have been told that a baby you miscarried had trisomy 22, rest assured that the miscarriage was not your fault and there was nothing you could have done to prevent it.[verywell.com]
  • Health Care Guidelines for Individuals with Down Syndrome: 1999 Revision (Down Syndrome Preventive Medical Check List). Down Syndrome Quarterly.[en.wikibooks.org]

References

Article

  1. Sinet PM, Théophile D, Rahmani Z, et al. Mapping of the Down syndrome phenotype on chromosome 21 at the molecular level. Biomed Pharmacother. 1994;48(5-6):247-252.
  2. Korbel JO, Tirosh-Wagner T, Urban AE, et al. The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies. Proc Natl Acad Sci U S A. 2009;106(29):12031-12036.
  3. Lyle R, Béna F, Gagos S, et al. Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21. Eur J Hum Genet. 2009;17(4):454-466.
  4. Park JP, Wurster-Hill DH, Andrews PA, Cooley WC, Graham JM Jr. Free proximal trisomy 21 without the Down syndrome. Clin Genet. 1987;32(5):342-348.
  5. Prandini P, Deutsch S, Lyle R, et al. Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance. Am J Hum Genet. 2007;81(2):252-263.
  6. Renna MD, Pisani P, Conversano F, et al. Sonographic markers for early diagnosis of fetal malformations. World J Radiol. 2013;5(10):356–371.
  7. Agathokleous M, Chaveeva P, Poon LC, Kosinski P, Nicolaides KH. Meta-analysis of second-trimester markers for trisomy 21. Ultrasound Obstetrics Gynecol. 2013;41(3):247–261.
  8. Kagan KO, Wright D, Baker A, Sahota D, Nicolaides KH. Screening for trisomy 21 by maternal age, fetal nuchal translucency thickness, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol. 2008;31(6):618-624.
  9. Summerfield P. Prenatal screening for Down's syndrome: balanced debate needed. Lancet. 2009;373(9665):722.

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Last updated: 2018-06-22 05:42