Sindrome di Down

What is Down's syndrome?

Children with Down's syndrome have multiple malformations, medical conditions and cognitive impairment because of the presence of extra genetic material from chromosome 21. The Down's syndrome phenotype is variable and the degree of cognitive impairment may be mild, moderate or severe. Children with Down's syndrome often function more effectively in social situations than would be predicted on the basis of their cognitive assessment results.¹

Primary care can play an integral role in parental support, diagnosis, initial management, treatment of common medical problems and health promotion for children with Down's syndrome.²

The most common cause of Down's syndrome is the additional copy of an entire chromosome 21. In about 88% of cases, the extra copy is maternally derived, through an error in cell division called non-dysjunction. The extra chromosomal content can occur through different mechanisms and at different points during the formation of germ cells. Non-dysjunction can occur during meiosis or from a mitotic error.

Down's syndrome can also occur when only a segment of chromosome 21 has three copies (partial trisomy) or when the whole chromosome is triplicated but only a proportion of the cells are trisomic (mosaicism) with other cells being normal. Mosaicism is found in about 1.3-5% of cases but it is possible that mosaicism occurs more frequently.

Translocation is another mechanism leading to Down's syndrome. Some of the genetic material from chromosome 21, usually from the long arm, is moved to chromosome 14 or 22, or from the long to the short arm of chromosome 21. Translocation occurs in about 4% of cases of Down's syndrome.

Incidenza

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.

• Mosaicism (2.4%) and translocations (3.3%) also occur.

• 75% of these translocations are de novo errors.

Fattori di rischio

• Family history of Down's syndrome.

• Maternal age is the strongest risk factor for Down's syndrome and the maternal age-specific risk of having a baby with Down's syndrome.

• The average maternal age-specific risk was calculated from live births in England and Wales between 1938 and 2010 for each age group and found to be:⁶

  • 0.66 per 1,000 for maternal age under 20 years of age.

  • 0.70 per 1,000 for ages 20-24.

  • 0.84 per 1,000 for ages 25-29.

  • 1.48 per 1,000 for ages 30-34.

  • 4.72 per 1,000 for ages 35-39.

  • 15.22 per 1,000 for ages 40-44.

  • 30.71 per 1,000 for 45 years and older.

At birth there is a wide range of associated physical features with Down's syndrome. Not all babies have typical facies. Frequently the first feature noticed is hypotonia.

Neonatal features of Down's syndrome⁷

• All newborns with Down's syndrome should undergo screening for cardiac, feeding, vision, hearing, thyroid and haematological abnormalities as soon as possible.

• 50% of newborns with Down's syndrome have a congenital heart defect that is often undetectable on prenatal ultrasonography; an echocardiogram is essential.

• Marked hypotonia or other feeding difficulties should prompt a radiographic swallowing assessment.

• Red reflex testing should be performed to check for congenital cataracts.

• A standard objective hearing screening using brainstem auditory evoked response or otoacoustic emission is recommended.

• Screening for subclinical thyroid disease using TSH and free thyroxine levels should be performed.

• FBC should be performed because of the increased risk of transient myeloproliferative disorder, leukaemoid reaction and polycythaemia.

Children and adults with Down's syndrome will often need regular reviews with regard to specific associated conditions (see below). People with Down's syndrome should also have an annual review to include an assessment of feeding, bowel and bladder function, any behavioural disturbance, vision and hearing and any other health concern.

There is a significant risk of a number of conditions, including hearing loss, obstructive sleep apnoea, otitis media, eye disease (including cataracts and severe refractive errors), congenital heart defects, neurological dysfunction, gastrointestinal atresias, hip dislocation, thyroid disease and (less commonly), transient myeloproliferative disorder, leukaemia and Malattia di Hirschsprung.¹

Cardiological disorders

The most common cardiac abnormalities are:

• Atrioventricular canal defects.

• Ventricular septal defect.

• Isolated secundum atrial septal defects.

• Isolated persistent patent ductus arteriosus.

• Fallot's tetralogy.

Adult patients, without known cardiopatia congenita, may develop mitral valve prolapse o aortic regurgitation. A second assessment in early adulthood may be appropriate.

Ear, nose and throat disorders

• 90% of patients with Down's syndrome may have conductive, sensorineural, or mixed hearing loss.⁵

• They are more susceptible to otitis media, sinusitis and pharyngitis.

• Obstructive sleep apnoea may develop.

Ophthalmological disorders

Most commonly:

• Cataracts

• Refractive errors

• Strabismus

• Nystagmus

• Congenital glaucoma

• Keratoconus

Gastrointestinal disorders

• Oesophageal atresia or tracheo-oesophageal fistula (tracheal abnormalities also¹² ).

• Duodenal atresia.

• Stenosi pilorica.

• Meckel's diverticulum.

• Malattia di Hirschsprung.

• Imperforate anus.

• Gastro-oesophageal reflux.

• Dental problems - delayed and unusual patterns of eruption; missing teeth.

• Malattia celiaca occurs frequently enough for screening to be recommended.

Orthopaedic disorders

• Atlanto-axial instability*.

• Hyperflexibility.

• Scoliosis.

• Hip dislocation after two years.

• Patellar subluxation or dislocation.

• Foot deformities.

*Few need treatment.¹³ They present with neck pain, limited movements or symptoms/signs suggestive of cord compression. Less specific symptoms - eg, bladder problems, gait abnormalities or clumsiness - may also indicate need for further investigation.

Disturbi endocrini

These are common, particularly ipotiroidismo. Annual TFTs are indicated.² Screening for diabetes is also recommended.⁹

Neurological and psychiatric disorders

• Learning difficulties (these range from severe, to those with 'low normal' IQ).

• Behavioural problems.

• Seizures occur in 5-10%.

• In older patients an Alzheimer's-type picture develops in >60% of those over 60 years of age.

Haematological disorders

• Patients have approximately 12 x greater risk of infections (eg, polmonite) due to impaired cellular immunity.

• They also have increased risk of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and acute megakaryoblastic leukaemia (AMegL).

• Polycythaemia and transient myeloproliferative disorder (a self-limiting type of leukaemia which regresses spontaneously by the age of 2 months) may occur in newborns.

• The survival of people with Down's syndrome has dramatically increased in the past few decades, largely as a result of improved surgical repair of congenital heart defects.

• Until the 1970s, the median age at death for children with Down's syndrome was less than 10 years leading up to the 1970s but 80% of affected individuals now survive into adolescence, with a median age at death in their mid-50s.

• Increased longevity increases the likelihood of fertility issues requiring support.¹⁴

• The leading causes of death in adults with Down's syndrome are respiratory infections and cardiac causes (including the consequences of congenital heart disease).

• The development of dementia is particularly common between the age of 30-40 years, contributing to nearly one third of deaths.¹⁵

• Apart from childhood leukaemia, the incidence of malignancy (haematological and solid tumours) is low in all age groups with Down's syndrome.

• The risk of cardiovascular disease remains lower than in the general population without Down's syndrome but increases to 13% in adults aged 50 years or older.

Vedi il Prenatal Screening for Down's Syndrome articolo.