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- Weijerman, M.E. & de Winter, J.P. Eur J Pediatr (2010) 169: 1445. doi:10.1007/s00431-010-1253-0
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Down syndrome (DS) is one of the most common chromosomal abnormalities. Because of medical advances and improvements in overall medical care, the median survival of individuals with DS has increased considerably. This longer life expectancy requires giving the necessary care to the individual with DS over their total longer lifespan. DS medical guidelines are designed for the optimal care of the child in whom a diagnosis of DS has been confirmed. We present an overview of the most important issues related to children with DS based on the most relevant literature currently available.
KeywordsDown syndrome Children Guideline Care Trisomy 21 Congenital abnormalities
Obstructive sleep apnea syndrome
Respiratory syncytial virus
Urinary tract anomalies
Anti-tissue transglutaminase antibodies
Human leukocyte antibodies
Down syndrome (DS) is the most common chromosomal malformation in newborns. In Europe, DS accounts for 8% of all registered cases of congenital anomalies. Throughout the world, the overall prevalence of DS is 10 per 10,000 live births, although in recent years this figure has been increasing. To a large extent, the prevalence of DS depends on several socio-cultural variables. In countries where abortion is illegal such as Ireland and the United Arab Emirates, its prevalence is higher. Conversely, in France, DS prevalence is low, and this is probably due to a high percentage of DS pregnancy terminations [6, 21, 33]. In The Netherlands, the most recent measure of DS prevalence was 16 per 10,000 live births . In the United Kingdom, the prevalence of pregnancies affected by DS has increased significantly, but there has been no overall change in the live birth prevalence of DS. Increasing maternal age and improved survival rates for infants with Down syndrome have outweighed the effects of prenatal diagnosis followed by the termination of pregnancy and a declining general birth rate [6, 14, 24, 33, 36].
DS is characterized by several dysmorphic features and delayed psychomotor development. Children with DS also have an increased risk of concomitant congenital defects and organic disorders such as congenital heart and gastrointestinal defects, celiac disease and hypothyroidism . The median age at death of individuals with DS has risen significantly in the US, from 25 years in 1983 to 49 years in 1997. Congenital heart defects (CHD) and respiratory infections are the most frequently reported medical disorders on death certificates for individuals with DS . Standardized mortality odds ratios (SMORs) in DS were low for malignancies except for leukaemia and testicular cancer, which were seen more often in individuals with DS [21, 39]. Recent decades have seen a substantial increase in the life expectancy of children with DS. In The Netherlands, the infant mortality rate in children with DS dropped from 7.07% in 1992 to 4% in 2003 (this is in contrast with the 0.48% infant mortality of the reference population in The Netherlands in 2003) . The fall in DS mortality was mainly related to the successful early surgical treatment of CHD and to the improved treatment of congenital anomalies of the gastrointestinal tract . The life expectancy of children with DS is primarily dependent on the risk of mortality in the first year of life. While modern medical care has reduced the mortality rate to more acceptable values, both morbidity and mortality could be further reduced. In this respect, respiratory infections and neonatal problems are the most important issues to be solved.
Since children with DS now have an improved life expectancy, the total population of individuals with DS is expected to grow substantially. Preventive health care programmes for these children will contribute to the improvement of their overall outcome and quality of life; therefore, it is very important to keep the medical guidelines updated [11, 21].
Characteristics of Down syndrome and specific clinical signs at birth
Most reliable and discriminative signs
Wide space in between the 1st and 2nd toe (“Sandal gap”)
Small internipple distance
Nuchal skin fold
Reliable and discriminative signs
Upward slant of the eye split
Transverse line in the palm of the hand (“Simian fold”)
Difficult to differentiate
Low, flat nose bridge
Initial postnatal support
Prevalence of medical problems in children with Down syndrome
Congenital heart defects
Obstructive sleep apnoea syndrome
Wheezing airway disorders
Congenital defects of gastrointestinal tract
Transient myeloproliferative disorder
Urinary tract anomalies
The prevalence of CHD in neonates with DS is about 44–58% worldwide. Atrioventricular septal defect and ventricular septal defect are the most common forms of CHD, constituting up to 54% for ASD and to 33% for VSD, of all CHDs in children with DS [31, 33]. A normal neonatal examination in children with DS does not exclude a serious CHD. Because of the high incidence of significant CHD in children with Down syndrome, early recognition of CHD is necessary as it can lead to the optimal management of the defect and can sometimes prevent the development of pulmonary hypertension. The surgical correction of significant defects usually takes place at the age of 2–4 months, though it is sometimes performed earlier (e.g. in cases of Tetralogy of Fallot). An elevated incidence (5.2–13.7%) of persistent pulmonary hypertension of the neonate (PPHN) with DS has recently been established, and there should be a specific focus on this condition after birth . Early assessment of the cardiac condition of neonates with DS should always be performed by echocardiography in the first month of life [8, 21, 35].
Ear, nose and throat disorders
Hearing impairment and otologic problems are prevalent in children with DS, and these problems correlate substantially with developmental problems. Midface hypoplasia is common in children with DS and consists of abnormalities of the nasopharynx, abnormal Eustachian tube anatomy, abnormal tooth development and agenesis of the teeth. These mid-face problems, together with hypotonia and macroglossia (children with DS have a relatively large tongue compared to the oral cavity), are responsible for chronic middle ear disease and chronic rhinorrhoea.
Gastrointestinal tract disorders
Congenital defects of the gastrointestinal tract are present in 4–10% of children with DS and play an important role in morbidity during the first year of life. These defects include oesophageal atresia/trachea-oesophageal fistula (0.3–0.8%), pyloric stenosis (0.3%), duodenal stenosis/atresia (1–5%), Hirschsprung disease (1–3%) and anal stenosis/atresia (<1–4%).These defects are more frequent in the DS population, as much as 25–30% of all cases of duodenal defects are in children with DS . Coeliac disease (CD) is another DS-specific disorder and is seen in 5–7% of children with DS, a rate that is ten times higher than in the normal population . Screening for early detection of CD in the DS population, with the aim of starting treatment and preventing complications from untreated CD such as failure to thrive, anaemia, osteoporosis and malignancy, seems to be justified. For CD screening in children with DS, we recommend human leukocyte antibodies (HLA)-DQ2 and HLA-DQ8 typing in the first year of life with buccal swabs, if available, which have the benefit of avoiding the unpleasant collection of blood. Children who have negative results for HLA-DQ2 or DQ8 (approximately 60%) can be excluded from further screening, and parents can be reassured that their child has no risk of CD. The remaining children need to be monitored for CD by using IgA anti-endomysium (EMA) and anti-tissue transglutaminase antibodies (anti-tTGA) beginning at 3 years of age [15, 38].
The prenatal occurrence of an aberrant right subclavian artery (ARSA, arteria lusoria) is substantially increased in patients with DS where it is found in up to 19–36%. ARSA may cause problems with the passage of solid food through the oesophagus and dysphagia. Moreover, impaired oral motor function, gastro-oesophageal reflux or congenital disorders have to be considered as a cause in feeding problems in children with DS [9, 22].
Constipation is a serious problem in children with DS and is mainly a consequence of the hypotonia; however, in serious cases, Hirschprung disease must be excluded .
Breastfeeding should be promoted not only because of the psycho-emotional or immunity benefits but particularly because breastfeeding has specific advantages for children with DS in terms of stimulating the development of the oral motor system . However, because of their impaired oral motor function, children with DS can have problems with drinking, swallowing and chewing.
Overweight and overnutrition deserve serious attention in children with DS .
Haemato-oncological and immunological disorders
In neonates with DS, the Gaussian distribution of thyroxin and TSH values are shifted to the left, and there may be a DS-specific thyroid dysregulation. Thyroxin has been given to newborns during the first 24 months, and although short-term follow-up showed some benefit to development and growth, there is no data available on the long-term benefit of treating these children with thyroxin [10, 28, 29]. Therefore, this treatment is not commonly used.
Thyroid disorders have been reported in up to 28–40% of children with DS, and they increase in frequency, up to 54%, as the children age [10, 15, 28]. Thyroid abnormalities in children with DS range from congenital hypothyroidism (1.8–3.6%) to primary hypothyroidism, autoimmune (Hashimoto) thyreoiditis (0.3–1.4%) and compensated hypothyroidism (25.3–32.9%). In addition, hyperthyroidism (Graves’ disease) (0–2%) occurs in children with DS as well. Compensated hypothyroidism or isolated raised thyroid stimulating hormone (IR-TSH) is most frequently present in children with DS and is characterized by mildly elevated TSH with normal or low normal free T4; it often has a self-limiting natural history . These thyroid antibodies are the second most frequently present, and when present, they can cause manifest hypo-or hyperthyroidism within 2 years in almost 30%, but these antibodies are as such not primary related to abnormal thyroid function [10, 15, 28]. Most predictive of the development of hypothyroidism is the presence of both elevated TSH and antibodies, and those children should be tested more frequently than other children with DS . When both are normal in the first decade of life, there is a low probability of hypothyroidism in the second decade . Interestingly, diabetes mellitus develops more frequently (1%) in children with Down syndrome [21, 30].
Children with DS have their own growth pattern and DS-specific growth curves .The follow-up of length and weight in children with DS should be part of the regular medical screening and special attention for the weight is warranted because children with DS are prone to overweight. Their lack of feeling of satisfaction and their unlimited food intake, as well as their moderate exercise pattern, need special attention .
Acquired hip dislocation occurs in up to 30% of children with DS and needs special attention. Patellofemoral instability is estimated to occur in 10–20% of children with DS; slipped capital femoral epiphysis is seen more often in children with DS and has a poor prognosis . Most of these disorders manifest themselves once children with DS start walking, around 2–3 years of age . An arthropathy similar to juvenile rheumatoid arthritis can develop in children with DS but is rare . The delay in motor development in children with DS is more pronounced than the delay in mental development. Delays in motor development appear to be particularly related to the degree of hypotonia, which negatively influences development and leads to problems in postural control and to typically static and symmetrical movement patterns, compensatory movement strategies, and lack of movement variability. Limitations in the functional activities of 5 to 7-year-old children with Down syndrome seem to be more related to the level of motor ability than to the level of performance of mental ability . Special attention to motor development and counselling by a physiotherapist is advised.
DS directed physiotherapy supports the development of the basic gross motor skills properly by challenging the children with DS and giving them confidence in their own physical abilities by making use of the knowledge of the typically movement patterns of DS, furthermore to support parents to start active play and sports.
Urinary tract disorders
Children with DS have significantly more risk of urinary tract anomalies (UTAs) (3.2%). Symptoms may be masked because voiding disturbances and delayed toilet training are usually interpreted as a consequence of delayed psychomotor development. UTAs such as hydronephrosis, hydroureter, renal agenesis and hypospadias must be considered in children with DS. Routine screening by ultrasound is not yet standard, but paediatricians should not overlook this problem .
There are no specific guidelines towards the attitude in delay in daytime and nighttime continence in children with DS; besides the standard treatment, visual instruction is helpful as well as showing them how to do. The advice is to start training at the moment the child can sit properly and understand the items stool, urine and toilet.
In adolescent girls with DS, the onset of puberty is similar to that of other adolescents. In boys with DS, the primary and secondary sexual characteristics and pituitary and testicular hormone concentrations are similar to those in typical adolescents . Females with DS are able to have children, but males with DS have a diminished capacity to reproduce . Education to prevent pregnancies is warranted, specific in children with DS who discuss sexuality open-hearted. In girls, contraception can only be discussed when their mental development enables them to understand the subject.
Furthermore, contraception can be given to prevent pregnancy or when there are problems with the menstrual cycle, for fear of blood or problems with the hygiene.
Unfortunately one must be cautious for sexual abuse in girls with DS.
Dermatologic diseases are often present and are especially troublesome in adolescents . Alopecia areata (2.9–20%), vitiligo (1.9%), seborrhoeic eczema (8–36%), folliculitis (10.3–26%) and syringoma (12.3–39.2%) are more frequently seen in children with DS. Rare but DS-specific problems are elastosis perforans serpiginosa and milia-like idiopathic calcinosis cutis [18, 23]. A previously reported high prevalence of atopic dermatitis (AD) in up to 56.5% of children with DS is probably an overestimation, as more recent studies suggest a lower prevalence of 1.4–3%. This could be the result of new and different diagnostic criteria for AD. This observation also notes a lower allergy risk in children with DS, which is in concordance with the studies on allergic rhinitis [17, 18, 23].
Most children with DS function in the low range of typical development, and their intelligence quotient decreases in the first decade of life. In adolescence, cognitive function may reach a plateau that persists in adulthood. Mental development shows a deceleration between the ages of 6 months and 2 years . IQ values vary, usually ranging from 35 to 70, indicating mild to moderate mental impairment; severe mental impairment is only occasionally seen in children with DS . Counterproductive behaviour and avoidance tactics can impede learning, and language production is often substantially impaired. Delayed verbal short-term memory and expressive language indicate the need for a special approach to teaching these children to speak (for example, learning to speak by first learning to read) [15, 21]. Furthermore, impaired oral motor function can influence articulation.
Children with DS have more pronounced neuro-behavioural and psychiatric problems, found in 18% to 38%. The most frequent problems are disruptive behaviour disorders, such as attention deficit hyperactivity disorder (6.1%), conduct/oppositional disorder (5.4%) or aggressive behaviour (6.5%), and obsessive–compulsive disorders. More than 25% of adults with DS have a psychiatric disorder, most frequently a major depressive disorder (6.1%) or aggressive behaviour (6.1%) [15, 21]. A diagnosis of autism or autism spectrum disorders in children with DS is found in 7%. This diagnosis is not easily made in children with DS mainly because of the resemblance and overlap of DS-specific behaviours and autism.
Epilepsy is seen in 8% of children with DS, with 40% occurring in infancy and often presenting as infantile spasms. Alzheimer’s disease which is associated with DS appears later in life, not in childhood .
Education and school
Early intervention education systems are programmes that can be used from the first months of life and provide tools to stimulate the development of children with DS, especially in the preschool period. Children with DS often begin primary school with extra support; successful outcomes are mainly in the area of social skills as a result of the ability to copy and mirror behaviour. The outcome for adult social independence depends largely on the development of abilities to complete tasks without assistance, the willingness to separate emotionally from parents and access to personal recreational activities .
Conclusion and recommendations
Screening schedule for children with Down syndrome 0–18 years
Timeline for medical assessment of children with Down syndrome
Once, after birth
Follow-up depends on the heart defect
Every 3 years
Polysomnography at 3–4 years
Every 3 years TGA, once HLA-DQ2 and 8b
Specific Downcurves- length/weight
TMD at first, leukaemia mainly first 5 years
neurologic screening, care during intubation
Most impact in first 4 years
Until speech is well established
The authors would like to thank Roel Borstlap, former paediatrician of the Assen Down clinic, for his constructive remarks. The authors were pleased to use the photos of the children with Down syndrome. Parental permission was obtained to publish the photos of the children, photography by www.fluitekruidje.nl.
There are no conflicts of interest.
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