Down’s syndrome

Published on 02/04/2015 by admin

Filed under Internal Medicine

Last modified 22/04/2025

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236 Down’s syndrome

Instruction

Look at this patient.

Salient features

History

• Ask the mother at what age she delivered the child (it occurs once in 1550 live births in women under the age of 20 years, in contrast to 1 in 25 live births for mothers over the age of 45 years).

Examination

• Collapse of the bridge of the nose

• Low-set ears

• Epicanthic folds

• Look at the iris for Brushfield’s spots: yellow speckles seen in young children

• Tell the examiner that you would like to:

• examine the hands for simian palmar crease (Fig. 236.1)
• examine for short inward curving of the little finger (Siegert’s sign)
• examine the heart for murmur of mitral regurgitation (endocardial cushion defects) and atrial septal defect (ASD; ostium primum type)
• check mental status quotient (MSQ) and formal IQ testing (80% have an IQ between 25 and 50)
• examine the foot for ankle pronation and pars planus (Fig. 236.2).

• Tell the examiner that you would like to check for hypothyroidism and thyroid antibodies

image

Fig. 236.1 Simian crease.

image

Fig. 236.2 Ankle pronation, loss of arch as a result of ligamentous laxity and pes planus.

(With permission from Davidson 2008.)

Diagnosis

This patient has features of Down syndrome (lesion), which is usually caused by trisomy 21 (aetiology) and is associated with a reduced life expectancy (functional status).

Questions

What complications can be seen in such patients?

• Increased incidence of acute leukaemia

• Presenile dementia of Alzheimer type (occurs in the fourth and fifth decades and reduces life expectancy)

• Atlantoaxial subluxation

• Duodenal atresia in children.

What are the broad management principles of such a patient?

• Evaluation:

• Echocardiography
• Sight
• Hearing.

• Prevention:

• Obesity
• Periodontal disease.

• Monitoring:

• Coeliac disease
• Thyroid function.

• Vigilance:

• Diabetes
• Leukaemia
• Arthritis
• Obstructive sleep apnoea
• Seizures
• Atlantoaxial subluxation.

• Other:

• Sexual and reproductive health
• Skin problems
• Behaviour problems
• Development.

Advanced-level questions

Mention two chromosomal abnormalities seen in this condition

• Trisomy 21 (N Engl J Med 1991;324:872)

• Mosaicism (46,XY/47,XY, +21). Approximately 1% are mosaics from mitotic non-dysjunction.

What are the underlying genetic mechanisms?

• Non-dysjunction (occurs during meiosis, particularly in the ovum, and correlates with maternal age)

• De novo translocation

• Familial translocation, usually robertsonian translocation of the long arm of chromosome 21 to another acrocentric chromosome, e.g. 22 or 14.

A 41-year-old woman, gravida 1, seeks prenatal care at 8 weeks of gestation. Her family history and medical history are unremarkable. What would you advise regarding her risk of foetal chromosomal abnormalities such as Down syndrome and her options for prenatal screening and diagnosis?

First trimester screening:

• Measurements of two biochemical markers: pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotrophin (hCG)

• Measurement of nuchal translucency

• Non-visualization of the nasal bone on ultrasonographic examination in the first trimester has been associated with an increased risk of Down syndrome and other aneuploidies.

Second trimester screening

Quadraple screening: maternal α-fetoprotein levels, hCG, unconjugated oestriol, inhibin A. Trisomy 21 is associated with high maternal levels of hCG and inhibin A and low levels of α-fetoprotein and unconjugated oestriol. Quadraple screening has a detection rate of 80% for trisomy 21 at a positive screening rate of 5% (a rate at or below this level is considered to be acceptable for aneuploidy screening).

Stepwise sequential screening during trimesters one and two

Stepwise sequential screening keeps the false positive rate low and provides early results to women with a positive test, but it combines the results of both the first-trimester and the second-trimester measurements into a final second-trimester risk assessment.

If a woman prefers to know with certainty that the foetus does not have Down syndrome or another form of aneuploidy, she may decide to bypass screening and choose either chorionic-villus sampling at 10 to 12 weeks of gestation (if available) or amniocentesis at 15 and 20 weeks of gestation.

Which maternal serum markers are used for prenatal screening of Down syndrome?

Serum α-fetoprotein, hCG and oestriol.

J Langdon Down (1828–1896) wrote an article in Clinical Lectures and Reports of the London Infirmary (now the Royal London Hospital) in 1866 entitled ‘The ethnic classification of idiots’. The extrachromosome was discovered by Lejeune in 1959.

T Brushfield (1858–1937), a British physician.

Ferdinand Siegert (1865–1946), a German paediatrician.

Mitchell in 1876 observed the increased incidence with maternal age and Penrose in 1933 confirmed it statisitically.

Hyman Isaac Goldstein (1887–1954), an American physician, described Goldstein’s sign, which is a wide space between the great toe and the adjoining toe seen in Down syndrome.

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