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Down syndrome
ОглавлениеThe availability of prenatal diagnosis and maternal serum screening for chromosomal abnormalities has also affected the birth frequency of Down syndrome. One French study of the impact of prenatal diagnosis over a 21‐year period (1979–1999) in a well‐defined population showed a drop of 80 percent in the birth prevalence of Down syndrome.110 A later report from the Paris Registry of Congenital Anomalies (2001–2005) noted a “fairly stable prevalence of Down syndrome (7.1 per 10,000 livebirths) over time.”111 A Scottish study aimed to assess the impact of prenatal diagnosis on the prevalence of Down syndrome from 1980 to 1996. Both births and pregnancy terminations were included. Pregnancy terminations for Down syndrome rose from 29 percent to about 60 percent.112 In contrast, the prevalence of Down syndrome noted by the Dutch Paediatric Surveillance Unit in 2003 was 16 per 10,000 livebirths, exceeding earlier reports and thought to reflect an older maternal age cohort.113 In the United States, a prevalence rate of 8.27 per 10,000 was reported in 2013 with an estimated 250,700 individuals.114, 115 In Europe, the 2009–2012 prevalence rate was 10.2 per 100,000 livebirths.116 In Japan, the estimated prevalence rate approximates 22 per 10,000 births.117 Many more babies with Down syndrome are born to women under rather than over 35 years of age. There is some evidence that the risk of having Down syndrome offspring in very young mothers is increased,118–121 but not in twin pregnancies.122
The special problems and associated defects in Down syndrome are well known, as is the increasing life expectancy. Studies from Japan,123 Denmark,124 England,125 Australia,126 and Canada127 highlight the increased life expectancy with Down syndrome. Baird and Sadovnick127 reported a large study of 1,610 individuals with Down syndrome identified in more than 1,500,000 consecutive livebirths in British Columbia from 1908 to 1981. They constructed survival curves and a life table for Down syndrome (Table 1.2) and for the general population.128 Their estimates show that 44.4 percent and 13.6 percent of liveborn individuals with Down syndrome will survive to 60 and 68 years, respectively, compared with 86.4 percent and 78.4 percent of the general population. In another report,129 the authors have analyzed the causes of death in Down syndrome, highlighting congenital defects and cardiovascular and respiratory illnesses as the most important. A UK population prevalence study noted a median life expectancy of 58 years in 2011.130
Table 1.2 Life expectancy with Down syndrome, between 1908–1981, to age 68 years.
| Age | Total | Survival at start of age interval (percent) |
|---|---|---|
| 5 | 1,020 | 81.05 |
| 10 | 841 | 78.40 |
| 20 | 497 | 75.34 |
| 30 | 91 | 72.12 |
| 40 | 136 | 69.78 |
| 50 | 57 | 60.68 |
| 55 | 31 | 53.96 |
| 60 | 16 | 44.44 |
| 68 | 1 | 13.57 |
Source: Baird and Sadovnick 1989.127 With permission from John Wiley and Sons.
Additional studies of mortality rates in individuals with Down syndrome revealed that those up to about 35 years of age were little different from others with intellectual disability. Thereafter, however, mortality rates in Down syndrome doubled every 6.4 years, compared with 9.6 years for other intellectually disabled individuals.129 Life tables constructed by these authors indicated a life expectancy of 55 years for a 1‐year‐old patient with Down syndrome and mild/moderate developmental delay and a life expectancy of 43 years for a 1‐year‐old patient with Down syndrome more profoundly affected.
A study from the CDC focused on the death certificates of 17,897 individuals with Down syndrome born between 1983 and 1997.131 These authors reported that the median age at death for those with Down syndrome increased from 25 years in 1983 to 49 years in 1997 (Figure 1.2).
Figure 1.2 Median age at death of people with Down syndrome by sex (upper), by racial group (middle), and with or without congenital heart defects (CHD) by racial group (lower).
Source: Yang et al. 2002.131 Reproduced with permission of Elsevier.
A 2009 Australian study found an overall survival figure for Down syndrome of 90 percent to at least 5 years of age.132 The known comorbidities of Down syndrome116, 133–149 and earlier onset Alzheimer disease133 cast a longer shadow. In individuals with Down syndrome over 40 years of age, increasing neuropsychological dysfunction and loss of adaptive skills have been noted.149 Between 50 and 70 percent develop Alzheimer disease by 60 years of age,139 and up to 84 percent of those with dementia develop seizures.136 People with Down syndrome who are APOEε4 carriers and/or have multiple comorbid disorders are at an increased risk of both dementia and death.150 A French study between 1979 and 1999 found a sixfold decreased risk of death from urological cancer in those with Down syndrome.146 People with Down syndrome have an overall decreased incidence of solid tumors.151
Table 1.3 reflects the common associated defects and complications that occur in Down syndrome, some of which can be anticipated, monitored, prevented, and treated.132–165 A EUROCAT population‐based register study between 2000 and 2010 in 12 countries analyzed 7,044 livebirths and fetal deaths with Down syndrome. That report152 noted that 43.6 percent of births with Down syndrome had congenital heart disease while 15 percent had another congenital malformation. The National Society of Genetic Counselors published valuable guidelines for communicating both prenatal and postnatal diagnoses of Down syndrome.166
Table 1.3 Defects and complications associated with Down syndrome132–165.
| Defect or complication | Prevalence (percent) |
|---|---|
| Neurologic | |
| Intellectual disability | 100 |
| Hypotonia | 100 |
| Alzheimer disease and dementia | 68–80 |
| Sleep disorders | 65 |
| Autism | 7–16 |
| Hearing impairment | |
| Conductive | 84 |
| Sensorineural | 2.7 |
| Mixed | 7.8 |
| Epilepsy | 5–13 |
| Psychiatric disorders | 11–30 |
| ADHD | 34 |
| Moyamoya disease | 3.8 |
| Unexplained regression | Unknown |
| Heart | |
| Mitral valve prolapse | 57 |
| Congenital heart disease | 44 |
| Aortic valve regurgitation | 17 |
| Pulmonary hypertension | 1.2–5.2 |
| Respiratory | |
| Airway problems | >16 |
| Immune system | |
| Susceptibility to infection | 100 |
| Juvenile rheumatoid‐like arthritis | 1.2 |
| Gastrointestinal | |
| Congenital defects of the gastrointestinal tract | 6 |
| Celiac disease | 5.4 |
| Dysphagia | 55 |
| Endocrine/metabolic | |
| Overweight/obesity | 23–70 |
| Hypothyroidism | 50 |
| Diabetes mellitus | 1.4–10.6 |
| Hyperthyroidism | 1–3 |
| Ophthalmologic | |
| Eye disorders a | 80 |
| Cataract | 17–29 |
| Keratoconus | 8–10 |
| Hematologic/oncologic | |
| Leukemia | 2–3 (>20‐fold excess) |
| Testicular cancer | Standardized incidence ratio of 2.9 |
| Transient myeloproliferative disorder | <10 (20–30% risk of AML) |
| Retroperitoneal teratoma | Increased |
| Anemia | 2.6–10.5 |
| Musculoskeletal | |
| Atlantoaxial instability | 10–30 |
| Osteoarthritis/low bone density | 8–28 |
| Atlantoaxial subluxation | 1–2 |
| Dental | |
| Tooth agenesis | 54 |
| Orthodontic problems | ±all |
| Periodontal disease | ±all |
| Dermatologic | |
| Hidradenitis suppurativa | 2 |
| Dermatologic disorders | 1.9–39.2 |
| Urinary tract | |
| Urinary tract anomalies | 3.2 |
a Includes strabismus, nystagmus, refractive errors, glaucoma, and lens opacities.
