Answers: Vitiligo and Hashimoto thyroiditis
Table 1: Reported prevalence of medical complications in adults with DS Medical Complication
Prevalence in Adult DS Population
<70% 4
Hearing loss
Obstructive sleep apnea
50% 4
Congenital Heart Defects
40 - 50%
Seizures
46% over 50 years 5
Thyroid disfunction Alzheimer’s disease
10%-40% 6,7
10% by 40 years 8 75% by 70 years
Mitral valve prolapse
57% 9
Celiac disease
10% 10
Cataract
8%-13% 11
Alopecia
3% 12
Down syndrome (DS) is themost common chromosome abnormality among liveborn neonates, occurring in 1 out of nearly every 700 live births. 1 Individuals with DS have a specific combination of phenotypic features that universally includes mental retardation. In 95% of cases, the cause of DS is chromosomal aneuploidy, Trisomy 21, but rare cases of DS can arise from either chromosomal translocation or from mosaicism. 2 DS is characterized by a wide variety of well- recognized dysmorphic features and many, well-known, congenital malformations including congenital heart defects in 40%-50% of cases. Though life expectancy in DS is shorter than that in the general population, survival has improved substantially, with a median age at death nearly doubling over the past 20 years to 56.8 years. 3 As such, awareness of adult-onset conditions and provision of medical services for adults with DS are becoming increasingly important. The patient reported here and the documented findings at autopsy further substantiate the need for a review of the more common pathologic features potentially seen in the adult DS population. A listing of medical problems, and their estimated prevalence, found more frequently in the adult DS population is shown in Table 1. A wide array of immunologic abnormalities have been associatedwith DS, including thymic atrophy, susceptibility to infections, and a higher incidence of autoimmune diseases that affect both endocrine (thyroid, pancreas, adrenal) and nonendocrine (stomach, small bowel) organs, including thyroiditis, diabetes, Addison disease, autoimmune hepa- titis, primary sclerosing cholangitis, and alopecia areata (occasionally in combination with vitiligo). 12-14 The link between DS and thyroid dysfunction is well established as the most common endocrine disorder in the DS population. 6 Studies suggest a lifetime prevalence of thyroid disorders on the order of 25%-30%, compared to a prevalence in the general population of less than 2%. 7 The variety of disorders ranges from congenital hypothyroid-
ism to autoimmune thyroiditis, including both Graves and Hashimoto disease. 7,15 Hashimoto thyroiditis, or chronic lymphocytic thyroiditis, as seen in the current case, however, is by the far the most common acquired thyroid disorder in DS and typically causes hypothyroidismwith or without detectable serum anti-thyroid antibodies at a median age of onset of 12.3 years and with an equal distribution in both male and female DS individuals. 16 The link betweenDS and vitiligo is less well-defined and appears to be tied not only to the concomitant presence of cutaneous alopecia areata (AA) but also to thyroiditis. The milder AA is reported in nearly 9% of DS individuals, while the more severe form of alopecia universalis, as was seen in the current case, is relatively rare at only 2% of DS patients. 12 The mechanismbehind the autoimmune predisposition in the DS population has yet to be determined; however, there are two proposed mechanisms that implicate the additional copy of chromosome 21. 15 There is a strong as- sociation between autoimmune hypothyroidism and the coding genes for the major histocompatibility complex (MHC) antigens expressed on B cells. While the MHC gene family region occurs on chromosome 6, it is postulated that genes on chromosome 21 participate in the upregulation of the MHC gene complex. 15 The second proposedmechanism involves the autoimmune regulatory gene (AIRE) located on chromosome 21. This gene is selectively expressed in the thymicmedulla and is hypothesized to be a protector against organ specific autoimmune disease. Inactivating mutations in the AIRE gene cause the rare autosomal recessive disease autoimmune polyendocrine syndrome type 1, a condition with a similar autoimmune profile to Down syndrome. Despite the additional AIRE gene copy in the DS, AIRE expression has recently been found to be paradoxically reduced in DS. 13,17 The current case illustrates many of the comorbid condi- tions known to challenge the adult DS community, which is
J La State Med Soc VOL 166 November/December 2014 273
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