Little is known about the pathogenesis of the phenotype in individuals with trisomy 21 mosaicism and Down syndrome. The primary goal of this study was to identify factors contributing to the observed phenotypic variation by evaluating 107 individuals having trisomy 21 mosaicism. To investigate a potential “threshold” effect due to trisomic imbalance, lymphocyte and buccal mucosa nuclei were scored using FISH. Overall, buccal cells showed a significantly higher frequency of trisomy than lymphocytes (P< 0.0001). Using latent class analysis, two phenotypic classes were identified based on the clinical findings of the propositi. Patients from class 1 had significantly fewer traits and a lower percentage of trisomic cells (mean of 37.3% lymphocytes; 34.5% buccal mucosa cells) when compared to those stratified into class 2 (54.0% lymphocytes; 53.4% buccal mucosa cells). Tissue-specific influences were also detected, with buccal mucosa trisomy levels being significantly correlated with IQ (P = 0.0094; both ectodermal derivatives), while congenital heart defects were significantly correlated with lymphocytes (P = 0.0286; both mesodermal embryonic derivatives). In conclusion, allowing for the distinction of two groups, we observed variation in phenotype, associated with the percentage of trisomic cells. We also observed tissue-specific effects on phenotype. The results of this study should enable geneticists and other health care professionals to provide information regarding optimal diagnostic approaches and anticipated clinical outcomes.

We investigated the association between seafood consumption and symptoms related to potential mercury toxicity in patients presenting to specialty medical clinics at Stony Brook Medical Center on Long Island, New York. We surveyed 118 patients from April–August 2012 about their seafood consumption patterns, specifically how frequently they were eating each type of fish, to assess mercury exposure. We also asked about symptoms associated with mercury toxicity including depression, fatigue, balance difficulties, or tingling around the mouth. Of the 118 adults surveyed, 14 consumed high mercury seafood (tuna steak, marlin, swordfish, or shark) at least weekly. This group was more likely to suffer from fatigue than other patients (p = 0.02). Logistic regression confirmed this association of fatigue with frequent high mercury fish consumption in both unadjusted analysis (OR = 5.53; 95% CI: 1.40–21.90) and analysis adjusted for age, race, sex, income, and clinic type (OR = 7.89; 95% CI: 1.63–38.15). No associations were observed between fish intake and depression, balance difficulties, or tingling around the mouth. Findings suggest that fatigue may be associated with eating high mercury fish but sample size is small. Larger studies are needed to determine whether fish intake patterns or blood mercury tests warrant consideration as part of the clinical work-up in coastal regions.

There was no evidence for gonadal mosaicism. It is important to confirm clinical hypotheses whenever possible.