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DYRK1A syndrome results from a reduction in copy number of the DYRK1A gene, which resides on human chromosome 21 (Hsa21). DYRK1A has been implicated in the development of cognitive phenotypes associated with many genetic disorders, including Down syndrome (DS) and Alzheimer's disease (AD). Additionally, overexpression of DYRK1A in DS has been implicated in the development of abnormal skeletal phenotypes in these individuals. Analyses of mouse models with Dyrk1a dosage imbalance (overexpression and underexpression) show skeletal deficits and abnormalities. Normalization of Dyrk1a copy number in an otherwise trisomic animal rescues some skeletal health parameters, and reduction of Dyrk1a copy number in an otherwise euploid (control) animal results in altered skeletal health measurements, including reduced bone mineral density (BMD) in the femur, mandible, and skull. However, little research has been conducted thus far on the implications of DYRK1A reduction on human skeletal health, specifically in individuals with DYRK1A syndrome. This review highlights the skeletal phenotypes of individuals with DYRK1A syndrome, as well as in murine models with reduced Dyrk1a copy number, and provides potential pathways altered by a reduction of DYRK1A copy number, which may impact skeletal health and phenotypes in these individuals. Understanding how decreased expression of DYRK1A in individuals with DYRK1A syndrome impacts bone health may increase awareness of skeletal traits and assist in the development of therapies to improve quality of life for these individuals. [ABSTRACT FROM AUTHOR]

Ts65Dn mice inherit a marker chromosome, T([17.sup.16]) 65Dn, producing segmental trisomy for orthologs of about half of the genes on human chromosome 21. These mice display a number of phenotypes that are directly comparable to those in humans with trisomy 21 and are the most widely used animal model of Down syndrome (DS). However, the husbandry of Ts65Dn mice is complicated. Males are sterile, and only 20-40% of the offspring of Ts65Dn mothers are trisomic at weaning. The lower-than-expected frequency of trisomic offspring has been attributed to losses at meiosis, during gestation and at postnatal stages, but no systematic studies support any of these suppositions. We show that the T([17.sup.16])65Dn marker chromosome is inherited at expected frequency and is fully compatible with development to midgestation. Disproportional loss of trisomic offspring occurs in late gestation and continues through birth to weaning. Different maternal H2 haplotypes are significantly associated with the frequency of trisomy at weaning in patterns different from those reported previously. The proportion of trisomic mice per litter decreases with age of the Ts65Dn mother. These results provide the first statistical and numerical evidence supporting the prenatal and perinatal pattern of loss in the Ts65Dn mouse model of DS.

Susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination (TMEVD), a mouse model for multiple sclerosis (MS), is genetically controlled. Through a mouse-human comparative mapping approach, identification of candidate susceptibility loci for MS based on the location of TMEVD susceptibility loci may be possible. Composite interval mapping (CIM) identified quantitative trait loci (QTL) controlling TMEVD severity in male and female backcross populations derived from susceptible DBA/2J and resistant BALBc/ByJ mice. We report QTL on chromosomes 1, 5, 15, and 16 affecting male mice. In addition, we identified two QTL in female mice located on chromosome 1. Our results support the existence of three linked sex-specific QTL on chromosome 1 with opposing effects on the severity of the clinical signs of TMEV-induced disease in male and female mice.

Feeding and swallowing disorders have been described in children with a variety of neurodevelopmental disabilities, including Down syndrome (DS). Abnormal feeding and swallowing can be associated with serious sequelae such as failure to thrive and respiratory complications, including aspiration pneumonia. Incidence of dysphagia in young infants with DS has not previously been reported. To assess the identification and incidence of feeding and swallowing problems in young infants with DS, a retrospective chart review of 174 infants, ages 0–6 months was conducted at a single specialty clinic. Fifty‐seven percent (100/174) of infants had clinical concerns for feeding and swallowing disorders that warranted referral for Videofluroscopic Swallow Study (VFSS); 96/174 (55%) had some degree of oral and/or pharyngeal phase dysphagia and 69/174 (39%) had dysphagia severe enough to warrant recommendation for alteration of breast milk/formula consistency or nonoral feeds. Infants with certain comorbidities had significant risk for significant dysphagia, including those with functional airway/respiratory abnormalities (OR = 7.2). Infants with desaturation with feeds were at dramatically increased risk (OR = 15.8). All young infants with DS should be screened clinically for feeding and swallowing concerns. If concerns are identified, consideration should be given to further evaluation with VFSS for identification of dysphagia and additional feeding modifications. [ABSTRACT FROM AUTHOR]