trisomy 21
Down syndrome (or trisomy 21) is the most common trisomy and also the commonest chromosomal disorder. It is a major cause of intellectual disability, and also has numerous multisystem manifestations.
Epidemiology
The approximate worldwide incidence is approximately 1 in 800live births . The individual risk is strongly dependent on maternal risk, and therefore incidence varies with regional and temporal variation in maternal age distribution and the implementation of antenatal screening.
Risk factors
- increased incidence with increasing maternal age
- translocation Down syndrome gene carriers
- previous pregnancy with Down syndrome
Clinical presentation
Diagnosis is often made antenatally and this must occur in conjunction with genetic counseling, which should begin prior to the testing.
In the postnatal period, characteristic phenotypical features point to the diagnosis:
- depressed nasal bridge
- epicanthal folds
- abundant neck skin
- macroglossia
- simian crease (single palmar crease)
- hypotonia
Intellectual disability becomes evident in early childhood as the failure to reach developmental milestones in an expected timeframe.
Pathology
In ~95% of cases, the chromosomal abnormality is trisomy of chromosome 21 due to meiotic non-disjunction (i.e. failure of a chromosome pair to separate during meiosis, so that both go to one daughter cell, and none to the other). Thus, the individual’s chromosome count is 47, rather than 46. Maternal non-disjunction accounts for ~95% of such cases.
An alternative chromosomal abnormality that results in the syndrome involves Robertsonian translocation of paternal chromosomal material, such that the overall number of chromosomes remains the same. This happens in ~3% of cases . Very rarely (~2%) some individuals have mosaic trisomy 21.
Clinicopathological spectrum
Neurological manifestations
Cognitive disability and epilepsy are the most common neurological manifestations . Structurally evident abnormalities include:
- cerebellar and vermian hypoplasia
- moyamoya syndrome
- Alzheimer disease developing in virtually all patients older than 40 years
- hippocampal volume loss: independent of age/dementia
- hearing loss from inner ear anomalies, e.g. semicircular canal dysplasia and dehiscence, narrowed internal acoustic canal, cochlear nerve canal stenosis, enlarged vestibular aqueduct
- intellectual disability: average IQ ranges ~50-70
Cardiovascular
Congenital heart disease affects ~40%. In particular, defects affecting the endocardial cushion are common:
- atrioventricular septal defect (AVSD): considered the commonest cardiac defect associated with Down syndrome
- ostium primum atrial septal defect (ASD)
- ventricular septal defect (VSD)
Respiratory
Gastrointestinal
- anal atresia
- celiac disease
- duodenal atresia
- Hirschsprung disease
- omphalocele
- diaphragmatic herniation
Musculoskeletal
- eleven ribs
- hypersegmented sternum
- joint laxity/dislocation(s)
- developmental dysplasia of the hip (DDH)
- atlantoaxial subluxation and atlantooccipital instability
- hypoplastic posterior arch of C1
- "mickey mouse" pelvis with flaring of iliac wings
- Kirner deformity
Endocrine
- thyroid dysfunction (4-8%)
- hypothyroidism (congenital, subclinical or acquired autoimmune and non-autoimmune)
- hyperthyroidism
- thyroid aplasia
Others
- significantly increased incidence of leukemia (although the individual may be protected against other solid organ tumors)
Radiographic features
The manifestations of Down syndrome are protean and can affect multiple systems. Some of these are better discussed under individual features in the wide clinicopathological spectrum of the condition (listed above).
Antenatal features
These are discussed in detail in a separate article.
Treatment and prognosis
Survival can be variable with the mean survival often considered at ~20 years-. Respiratory infections stay considerably predominant cause of death. Moreover, other causes of early mortality, include congenital heart defects and dementia
History and etymology
Down syndrome was named after John Langdon Haydon Down (1828-1896), an English physician .
Siehe auch:
- Atriumseptumdefekt
- Hüftdysplasie
- Lungenhypoplasie
- Herzfehler
- Analatresie
- Morbus Hirschsprung
- Duodenalatresie
- Moyamoya-Erkrankung
- Omphalozele
- trisomies
- atrioventricular septal defect (AVSD)
- atlantoaxiale Subluxation
- Trachealbronchus
- Makroglossie
- Morbus Alzheimer
- venricular septal defect
und weiter:
- Pätau-Syndrom
- Persistierender Ductus arteriosus
- Hypertelorismus
- obstetric curriculum
- Mikrolithiasis testis
- Ösophagusatresie
- Ebstein anomaly
- congenital tracheo-oesophageal fistula
- Tuberculum conoideum der Klavikula
- Hydrops fetalis
- Chylothorax
- Pancreas anulare
- Varianten der Herzanatomie
- anterior vertebral body beaking
- Klinodaktylie
- Auftreibung Metaphysen
- antenatal features of Down syndrome
- Kamptodaktylie
- chromosomale Anomalien
- fetal pleural effusion
- absent nasal bone
- CXR approach to congenital heart disease
- fetal hepatomegaly
- fetal hydronephrosis
- aneuploidy
- Brachymetatarsie
- fetal pyelectasis
- abnormal ductus venosus waveforms
- chest x-ray appeoach to congenital heart disease
- hypoplastic nasal bone
- Golfballphänomen
- nuchal thickness
- microtia
- orbital hypertelorism
- congenital heart disease - chest x-ray approach
- altered alpha fetoprotein levels
- choline:creatine ratio
- fetal hepatosplenomegaly
- kongenitale Kniegelenksluxation
- short umbilical cord
- antenatal screening
- endocardial cushion defect
- Erlenmeyer flask deformity of the femur
- verzögerte Skelettreifung
- Brachyzephalie
- dens erosion
- short maxillary length
- shortened fetal femoral length
- myo-inositol
- Acetabulumwinkel
- H-type tracheo-oesophageal fistula with no atresia
- shortened fetal humerus
- Ventrikelseptumdefekt
- atlantookzipitale Subluxation
- transient abnormal myelopoiesis
- Moyamoya-Muster
- Grisel-Syndrom
- prominentes Tuberculum conoideum der Klavikula
- Dottersacktumor der Glandula pinealis
- Mickey Maus Beckenschaufeln
- eponymous syndromes
- präpylorische Webstenose des Magens
- kongenitaler Hydrozephalus
- kongenitale Pulmonalstenose