1.1. General growth and developmental characteristics
Down syndrome is characterised by a general growth deficiency. According to anthropometric standards, deficiency in the rate of growth reduces in late childhood whereas weight is frequently increased during that period⁸. Distal portions of arms and legs are reported to be short in relation to whole body proportions⁹. For the majority, the cause of growth retardation is unknown¹⁰ but it is thought to be of multifactorial origin. Delayed growth has been linked to different anomalies and conditions, including congenital heart disease^11,12, sleep related upper airway obstruction¹³, nutritional inadequacy due to feeding problems and thyroid hormone deficiency^12,14. Growth retardation has also been associated with anomalies of insulin-like growth factors (IGF) and growth hormone (GH)¹⁵.

1.2. General musculoskeletal features
Hypotonia is one of the cardinal features in a newborn with Down syndrome even though general muscular tone improves with age16. Nevertheless, the orofacial complex remains hypotonic into later life producing functional and structural alterations^17,18
Atlantoaxial instability has implications for managing oral care, dental treatment and during general anaesthesia¹⁹. People with Down syndrome have a small risk for acute or chronic neurological problems caused by cervical spine instability^20,21. Between 12 and 20% of individuals with Down syndrome are diagnosed with atlantoaxial instability that can lead to spinal cord damage. Dentists and anaesthetists need to be aware and care must be taken in extending the neck to avoid dislocation^{3, 4, 21}.

1.3. Cardiovascular system
About 40 to 50% of infants with Down syndrome have some form of congenital heart disease, consisting of ventricular septal defects, A/V communications, arterial septal defects and patent ductus arteriosus³. Mitral valve prolapse has been shown to be more prevalent than in the general population and other minor structural and anatomical anomalies have also been described by means of echocardiography²³. There is an increased incidence of mitral valve prolapse and of aortic regurgitation in adults, which has implications for the prevention of infective endocarditis, particularly because of the high incidence of periodontal disease amongst this population^24,25. Antibiotic prophylaxis is advisable for any dental procedure to avoid the risk of bacterial endocarditis. It must also be remembered that despite a normal echocardiogram at birth, children with Down syndrome can develop heart disease at a later stage secondary to airway problems²⁶.

1.4. Haemopoietic system
Immunodeficiency is one of the conditions with the greatest repercussions on the oral health of individuals with Down syndrome. Neutrophil leukocytes are defective and short-lived, cell mediated immunity is impaired and serum immunoglobin patterns are disturbed²⁷. It has been reported that a higher percentage of institutionalised people with Down syndrome are carriers of the hepatitis B virus compared to their peers. This is believed to be related to a poor antibody response to the virus due to immunodeficiency^3,4.
Approximately 1 in 200 children with Down syndrome develop acute leukaemia⁴, particularly of the lymphocytic type. The risk for a person with Down syndrome of developing leukaemia is thought to be 20 to 30 times higher than in the general population²⁸. Dentists should be aware that there is a clinical correlation between the onset of disease and certain oral manifestations. Findings such as acute gingivitis, aggressive oral infection and/or ulceration may alert the professional to arrange further examination.

1.5. Nervous system
Structural anomalies. Most of the deficiencies in brain development occur during the first period of life, producing a reduction in cortical neurones and abnormal neurotransmission. These alterations are mainly related to the basal forebrain, the hippocampus and the cerebellar regions and may explain difficulties in short and long-term memory, speech and learning abilities^29,30.
Cognitive ability. Intellectual deficiency is present in varying degrees for most persons with Down syndrome. The majority has an IQ of between 40 and 60 (moderate retardation) although cognitive ability may range between normal intelligence and severe retardation³¹. Difficulties are greater for speech and expressive language skills than for visuospatial skills. Socialisation skills are high relative to cognition and communication abilities³².
Pain perception. For many years, observational reports suggested that persons with Down syndrome are insensitive to pain. Reduced pain responses following painful stimuli have been reported^33,34, such as lack of cry response, grimacing or retraction from the stimulus. This was initially thought to be due to underlying neurological deficiency³⁴. There is now evidence that persons with Down syndrome are not insensitive to pain but that they express their discomfort more slowly and imprecisely than controls³⁵.
Epilepsy. The prevalence of epilepsy in the Down syndrome population has been reported ranging from 1% to more than 13% according to different authors^36,37. The occurrence of seizures that continue on ageing may be defined as a syndrome feature³⁸. Pharmacological treatment is recommended to minimise detrimental effects.
Autism. There is co-morbidity between autism and Down syndrome, although this relationship might be explained by the strong link between intellectual deficiency and autism. The overall prevalence of autism is of around 5.5 per 10,000 persons, and approximately 1.3% of autists also have Down syndrome³⁹. The prevalence of autistic-like symptoms is higher, however, and up to one in 20 children with ds may be affected, although a diagnosis of true autism cannot always be made^40,41.

Alzheimer disease. Despite the lack of specific tests to determine Alzheimer diagnosis, progressive decrease in memory, speech, motor activities and continence in persons with Down syndrome may represent an analogue type of neuropathology³¹. Evidence of neurological degeneration and senile plaques, even in early adulthood, has strengthened the link between Down syndrome and Alzheimer disease, although conclusive evidence has not been produced for a common mechanism⁴². A high prevalence of the clinical manifestations of Alzheimer-type disease is noted in adults with Down syndrome after the age of 50, also related to depression and hypothyroidism⁴³. An overall tableau of precocious ageing is noted in Down syndrome ^31,34 but further research is needed to elucidate the mechanisms of this clinical observation.

1.6. Ocular and otorhinological characteristics
The commonest alterations of ocular function are strabismus, congenital eversion of the upper eyelids and refraction defects^45,46. However, congenital cataracts and acute keratocone are reported to be the main causes that lead to the loss of vision^47,48.
The chronic nature of ear, nose and throat problems among people with Down syndrome make parents aware of the frequent symptoms of hearing alterations and respiratory infections. In addition, there are anatomical and structural features of the mid-face and inner ear that maycontribute to the development of chronic disease. These conditions should be monitored regularly and be treated rapidly to avoid complications^49,50.
Most children with Down syndrome have mild to moderate hearing loss and there is increased incidence of conductive and sensorineural hearing loss in adolescents and adults^50,53. Hearing impairment can be successfully managed in this population but, if undiagnosed, is a significant cause of preventable secondary handicap^51,54.

1.7. Endocrine system
Although the majority of the population with Down syndrome present a hormonal production within average levels, a higher prevalence of endocrine anomalies is reported in this group, such as hypothyroidism, both compensated and congenital. Early diagnosis may help to reduce neuronal system compromise due to this problem^55,56. At all ages, thyroid disorder occurs more frequently than in the general population^57,58 and the prevalence increases with age⁵⁹. Biochemical screening is essential as, if left undiagnosed, thyroid disorder constitutes a risk of secondary disability⁵⁶.
Most males with Down syndrome are sterile due to hypogonadism, and fertility in the female population is reduced due to decreased ovocyte production⁶⁰. Reproduction is therefore rare but possible.