Down Syndrome

Down Syndrome (Trisomy 21)

Down syndrome or Down’s syndrome is a genetic disorder caused by an additional chromosome 21 material.

 

Epidemiology and Genetics

  • Incidence: The incidence is approximately 1 in 1000 live births in the UK, although this can vary by region. The risk remains higher with increasing maternal age, especially above 35 years.

  • Genetics:

    • Trisomy 21 (95%): Caused by meiotic non-disjunction, resulting in an extra copy of chromosome 21 (47, XX,+21 or 47,XY,+21).

    • Translocation (4%): A minority have a translocation of a chr21, most commonly a Robertsonian translocation, e.g., t(14;21). These individuals have a total of 46 chromosomes, but the risk of recurrence is higher, especially if a parent is a carrier.

    • Mosaicism (1%): A smaller percentage of individuals have mosaicism, with some cells having trisomy 21 and others having a normal karyotype.

 

Clinical Features

  • Features at birth:

    • Hypotonia

    • Brachycephaly with a flat occiput and excess neck skin

    • Upslanting palpebral fissures, epicanthic folds, and Brushfield spots in the iris

    • Short broad hands with a single palmar crease and clinodactyly (incurving of the fifth finger)

    • Wide sandal gap

    • Protruding tongue and high-arched palate

    • GI issues: Increased risk of duodenal atresia, annular pancreas, and Hirschsprung’s disease.

    • Haematological: Transient abnormal myelopoiesis (TAM) is common in newborns and can progress to congenital leukaemia (ML-DS). Polycythaemia may also be present.

    • Cardiac anomalies: Occur in around 40-50% of cases. The most common are atrioventricular septal defect (AVSD), followed by ventricular septal defect (VSD) and atrial septal defect (ASD).

 

Initial Investigations and Management

  • Newborn screening: The UK newborn blood spot screening programme screens for congenital hypothyroidism.

  • Diagnosis confirmation: A definitive diagnosis is made via karyotype analysis, or FISH (Fluorescence In Situ Hybridisation) for a rapid result.

  • Key investigations at birth/early infancy:

    • Full Blood Count (FBC): To screen for polycythaemia or transient abnormal myelopoiesis (TAM).

    • Thyroid Function Tests (TFTs): Repeat TFTs are recommended at 6 months, 12 months, and annually thereafter, or more frequently if clinically indicated.

    • Echocardiogram (ECHO): All newborns with a confirmed or suspected diagnosis should have an ECHO to exclude congenital cardiac disease, ideally before hospital discharge or within the first 6 weeks of life.

    • Hearing screen: All newborns are offered the Newborn Hearing Screening Programme. Given the high incidence of otitis media with effusion (glue ear), regular audiology follow-up is essential.

    • Vision screening: Screen for congenital cataracts and other anomalies. Referral to ophthalmology is recommended by 6 months of age.

  • Admission to NICU/SCBU (Special Care Baby Unit):

    • For cardiac failure or cyanosis.

    • For feeding difficulties, vomiting, or delayed meconium passage (to assess for GI issues).

    • For significant haematological concerns (e.g., symptomatic polycythaemia).

 

Ongoing Management and Surveillance

  • Signposting and counselling:

    • Provide up-to-date and balanced information. Use person-first language (“a child with Down Syndrome”).

    • Signpost families to national and local support groups like the Down’s Syndrome Association (DSA) and Down Syndrome UK (DSUK).

  • Growth monitoring: Use Down Syndrome-specific growth charts (DSMIG/RCPCH charts) to plot height, weight, and head circumference. This is crucial as their growth pattern differs from the general population.

  • Community and developmental clinic follow-up:

    • Hearing: Regular audiology follow-up is vital due to the high risk of conductive and sensorineural hearing loss.

    • Vision: Regular ophthalmology reviews are necessary to screen for common issues like cataracts, refractive errors, and nystagmus.

    • Hypothyroidism: Annual thyroid screening (TSH and T4) is required throughout life.

    • Coeliac Disease: The prevalence is much higher (up to 1 in 20). Screening should be performed with a low threshold for clinical suspicion, especially if there are new gastrointestinal symptoms or poor growth. Some guidelines recommend routine screening with TTG antibodies and total IgA from age 2 years.

    • Developmental support: Early intervention teams (Physiotherapy, Speech and Language Therapy, Occupational Therapy, Portage) are crucial for developmental support.

    • Cardiac monitoring: Continued cardiac follow-up if a defect is present.

    • Sleep: A sleep oximetry study should be considered if there are symptoms of Obstructive Sleep Apnoea (OSA).

    • Immunisation: Ensure the child is up-to-date with all routine UK immunisations, and advise on the annual influenza vaccine.

    • Atlantoaxial Instability: Discuss the signs and symptoms of cervical spine instability, a rare but important complication to be aware of.