Cohort Definition Name: “Down Syndrome”
Contributor name: Jill Hardin
Contributor OrcId: 0000-0003-2682-2187
Logic Description: Condition occurrence of Down Syndrome, starting between 0 days before and 0 days after cohort entry start date and ending between 0 days before and 0 days after cohort entry start date. Having at least 1 additional condition occurrence of ‘Down syndrome’, starting between 1 days after and 365 days after cohort entry start date; having no condition eras of ‘Condition_Era Pregnancy Codes’, starting between 0 days before and 0 days after ‘Down syndrome’ start date and ending between 0 days after and 0 days after ‘Down syndrome’ start date.
Recommended study application: outcome
Assertion statement: This cohort definition was executed on at least one real person-level observational health data source and resulted in a cohort with at least 1 person.
Submitted cohort definition:
DownSyndrome.txt (6.3 KB)
Target Clinical Description
Overview:
Down syndrome, also known as trisomy 21, is a chromosomal disorder caused by the presence of an extra copy of chromosome 21. It is the most common chromosomal anomaly and a leading cause of intellectual and developmental disabilities. Down syndrome is characterized by a range of physical features, developmental delays, and potential health issues that may vary in severity among individuals.
Presentation:
Down syndrome can be diagnosed during pregnancy, or diagnosed after birth.
If Down syndrome is diagnosed after birth, it is suspected based upon distinct physical features, including almond-shaped eyes, flattened nasal bridge, and small ears; short stature; and hypotonia (low muscle tone). Down syndrome is associated with intellectual and developmental disabilities, ranging from mild to moderate. People with Down syndrome are at increased risk of structural heart abnormalities, such as atrioventricular septal defects and ventricular septal defects. There is also increased risk for gastroesophageal reflux disease (GERD), feeding difficulties, celiac disease, duodenal atresia, and Hirschsprung’s disease. Hypothyroidism is common among individuals with Down syndrome. People with Down syndrome have increased susceptibility to respiratory infections and obstructive sleep apnea. There is also increased risk of developing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
Assessment:
Assessment of Down syndrome involves both screening and confirmatory testing. Screening tests include tests of the mother’s blood (eg, MS-AFP, Triple Screen, Quad-screen), and an ultrasound of the fetus evaluating for polyhydramnios. After a positive screening test, fetal blood is sampled via chorionic villus sampling, amniocentesis, or percutaneous umbilical cord sampling. Then a karyotype or chromosomal microarray analysis is performed to detect the presence of an extra chromosome 21.
Plan:
Following diagnosis, further evaluation is performed to assess for associated conditions, including echocardiography to screen for congenital heart defects, evaluation of thyroid function through blood tests, and assessment of cognitive and developmental milestones. Management includes monitoring of growth and nutrition. Speech, physical, occupational, and behavioral therapists are involved in management. Medical specialists are needed, depending upon the presence of associated conditions, and may include a pediatric cardiologist, endocrinologist, geneticist, and ophthalmologist.
Prognosis:
People with Down Syndrome are at risk for a variety of associated conditions, including cognitive delays, behavioral disorders, heart problems, thyroid disease, gastrointestinal problems, autism, and Alzheimer’s disease. People with Down syndrome need support and care throughout their life.
Diagnostics Evaluation:
Assessment of Down syndrome involves:
- Chromosome Analysis: Karyotyping or chromosomal microarray analysis to detect the presence of an extra chromosome 21.
- Physical Examination: Identification of characteristic physical features and associated health issues.
- Cardiac Evaluation: Echocardiography to screen for congenital heart defects.
- Thyroid Function Tests: Evaluation of thyroid function through blood tests.
- Developmental Assessment: Assessment of cognitive and developmental milestones.
Differential Diagnoses:
Conditions that could be mistaken for Down syndrome include:
- Other chromosomal disorders (e.g., trisomy 13, trisomy 18)
- Genetic syndromes with overlapping features (e.g., Noonan syndrome)
Treatment Plan:
The treatment plan for Down syndrome includes:
- Early Intervention: Occupational therapy, physical therapy, speech therapy, and special education to support developmental milestones.
- Healthcare Monitoring: Regular medical check-ups to manage associated health issues, including cardiac and thyroid evaluations.
- Surgical Interventions: Surgical correction of congenital heart defects and other surgical interventions as needed.
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Supportive Care: Addressing feeding difficulties, managing thyroid dysfunction, and providing care for respiratory and other health issues.
Prognosis: - Short-term Prognosis: Infants with Down syndrome may require medical interventions for associated health issues, such as congenital heart defects. Early intervention and supportive care can significantly improve developmental outcomes.
- Long-term Prognosis: With appropriate medical care, educational support, and social interventions, individuals with Down syndrome can lead fulfilling lives. Their prognosis depends on the severity of cognitive and health challenges, as well as the availability of comprehensive care.
Exclusions:
Conditions or treatments to rule out:
- Other chromosomal disorders
- Genetic syndromes with similar features
#Ambiguity:
Noonan Syndrome: A genetic disorder with some overlapping features but distinct genetic and clinical characteristics from Down syndrome.
Subtypes:
There are no specific subtypes of Down syndrome for this report.
References:
- Bull MJ, the Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics. 2011;128(2):393-406.
- Roizen NJ, Patterson D. Down’s syndrome. Lancet. 2003;361(9365):1281-1289.
- de Graaf G, Buckley F, Skotko BG. Estimation of the number of people with Down syndrome in the United States. Genet Med. 2017;19(4):439-447.
- Allanson JE. Noonan syndrome. J Med Genet. 1987;24(1):9-13.
- Skotko BG, Capone GT, Kishnani PS. Down syndrome diagnosis and treatment: The earlier the better. Pediatrics. 2020;145(4):e20193959.
- Antonarakis SE, Lyle R, Dermitzakis ET, Reymond A, Deutsch S. Chromosome 21 and down syndrome: from genomics to pathophysiology. Nat Rev Genet. 2021;22(4):235-251.
- Morris JK, Springett A. Greenlees R, et al. Trends in congenital anomalies in Europe from 1980 to 2012. PLoS One. 2018;13(4):e0194986.
Phevaluator results overview:
Phevaluator results shows the highest PPV results for the phenotype requiring a second code within 180 days of the first code. This definition decreases the sensitivity compared to the phenotype definition which requires only 1 code. The numbers of subjects identified in the two code phenotype is reduced by ~40% compared to the one code definition. There is a high degree of overlap between the two definitions.
We recommend use of cohort that requires two codes for Down syndrome.