Down's Syndrome Medical and Health News Headlines

Antioxidants do not improve early childhood development in children with Down's syndrome.

J Pediatr. 2008 Sep;153(3):441

Authors: Reynolds T

PMID: 18718269 [PubMed - in process]

Differential in vitro cytotoxicity does not explain increased host toxicities from chemotherapy in Down syndrome acute lymphoblastic leukemia.

Leuk Res. 2008 Aug 19;

Authors: Valle M, Plon SE, Rabin KR

Treatment-related toxicities such as mucositis and infections are both more frequent and more severe in children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) compared to non-DS ALL. Altered methotrexate pharmacodynamics play a role, but severe toxicities also occur in treatment courses that lack methotrexate. We hypothesized that this might be attributable to heightened cytotoxic effects of other ALL chemotherapeutic agents on DS versus non-DS host tissues. Panels of DS and non-DS lymphoblastoid cell lines (LCLs) and primary fibroblast cell lines were treated with asparaginase, dexamethasone, doxorubicin, mafosfamide and vincristine. LCL survival was assessed using the MTT assay, and fibroblast proliferation using the clonogenic survival assay. No significant differences were observed between DS and non-DS cell lines using either assay. Both DS and non-DS cell lines were resistant to dexamethasone at the maximal concentrations tested, and did not differ significantly in sensitivity to the other drugs studied. Thus, heightened in vitro cytotoxicity does not appear to account for the increased treatment-related toxicities observed in patients with DS ALL.

PMID: 18718659 [PubMed - as supplied by publisher]

Selective attention deficits associated with mild cognitive impairment and early stage Alzheimer's disease in adults with down syndrome.

Am J Ment Retard. 2008 Sep;113(5):369-86

Authors: Krinsky-McHale SJ, Devenny DA, Kittler P, Silverman W

Adults with Down syndrome and early stage Alzheimer's disease showed decline in their ability to selectively attend to stimuli in a multitrial cancellation task. They also showed variability in their performance over the test trials, whereas healthy participants showed stability. These changes in performance were observed approximately 2 years prior to a physician's diagnosis of possible Alzheimer's disease, which was made when they were exhibiting declines in episodic memory suggestive of mild cognitive impairment. Performance on this task varied with the evolution of dementia, showed modestly good sensitivity and specificity, and was relatively easy to administer. Given these qualities this task could be a valuable addition to a neuropsychological battery intended for the assessment of mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.

PMID: 18702557 [PubMed - in process]

Anti-amyloidogenic, anti-oxidant and anti-apoptotic role of gelsolin in Alzheimer's disease.

Biogerontology. 2008 Aug 15;

Authors: Chauhan V, Ji L, Chauhan A

Fibrillar amyloid beta-protein (Abeta) is a major component of amyloid plaques in the brains of individuals with Alzheimer's disease (AD) and of adults with Down syndrome (DS). Gelsolin, a cytoskeletal protein, is present both intracellularly (cytoplasmic form) and extracellularly (secretory form in biological fluids). These two forms of gelsolin differ from each other in length and in cysteinyl thiol groups. Previous studies from our and other groups have identified the anti-amyloidogenic role of gelsolin in AD. Our studies showed that both plasma and cytosolic gelsolin bind to Abeta, and that gelsolin inhibits the fibrillization of Abeta and solubilizes preformed fibrils of Abeta. Other studies have shown that peripheral administration of plasma gelsolin or transgene expression of plasma gelsolin can reduce amyloid load in the transgenic mouse model of AD. Our recent studies showed that gelsolin expression increases in cells in response to oxidative stress. Oxidative damage is considered a major feature in the pathophysiology of AD. Abeta not only can induce oxidative stress, but also its generation is increased as a result of oxidative stress. In this article, we review evidence of gelsolin as an anti-amyloidogenic agent that can reduce amyloid load by acting as an inhibitor of Abeta fibrillization, and as an antioxidant and anti-apoptotic protein.

PMID: 18704746 [PubMed - as supplied by publisher]

[Mothers' experience with their developmentally disordered children: specificity of internal representations]

Medicina (Kaunas). 2008;44(7):553-63

Authors: Pukinskaite R, Praninskiene R

The purpose of the present study was to examine mothers' internal representations of experience with their developmentally disordered children. Maternal perceptions of children have been considered important in clinical work with developmentally disordered children and their families. Using developmental disability sample of 17-34-month-old children, we compared mothers' representations of their children in clinically referred and not referred groups, using the Working Model of the Child Interview. Twenty mothers of children with developmental disorders and twenty matched controls participated. Six (30%) children of experiment group had a diagnosis of cerebral palsy; 5 (25%) were diagnosed with Down's syndrome, while the remaining 9 (45%) had a diagnosis of mixed specific developmental disorder. Many children with disability also were diagnosed with heart disease, epilepsy, and hydrocephalus. Maternal representations' measures were compared to their self-perceived impact of child disability on family, their sensitivity to child, and some demographic and family characteristics. Compared to controls, mothers of children with developmental disability had representations of their children that were significantly more likely to be classified distorted or disengaged (chi(2)=7.24; df=2; P<0.05). More severe disability status was significantly associated with mothers' disengaged representations, fear for safety of children, and intensity of involvement in care giving (P<0.05). The study did not confirm relationships between maternal representation classifications and their self-perceived impact of child disability on family. No differences were found concerning mothers' emotional empathy index in clinical and control groups. The differences in mean emotional empathy scores were related to many aspects of maternal internal representations and to some areas of self-perceived stress. The results of Working Model of the Child Interview did not correlate with child age and gender, birth order, and parents' level of education.

PMID: 18695353 [PubMed - in process]

Masticatory dysfunction in persons with Down's syndrome. Part 1: aetiology and incidence.

J Oral Rehabil. 2008 Aug 12;

Authors: Faulks D, Collado V, Mazille MN, Veyrune JL, Hennequin M

The functional and anatomical characteristics of Down's syndrome have direct repercussions on oral health. Orofacial dysfunction is on account of poor neuromotor control, muscle weakness, dental anomalies, dysmorphology and intercurrent illness. In particular, feeding and swallowing are impaired. The aim of this first article was to summarize the orofacial difficulties encountered by persons with Down's syndrome at all stages of life and to explain their aetiology. Indicators are proposed for the identification of masticatory problems within this population and reduced masticatory efficiency is discussed in relation to repercussions on oral and general health and on the social integration of persons with Down's syndrome. A second article will describe techniques for preventing, treating and compensating for masticatory dysfunction in this population.

PMID: 18702629 [PubMed - as supplied by publisher]

Maternal Global Methylation Status and Risk of Congenital Heart Diseases.

Obstet Gynecol. 2008 Aug;112(2):277-283

Authors: van Driel LM, de Jonge R, Helbing WA, van Zelst BD, Ottenkamp J, Steegers EA, Steegers-Theunissen RP

OBJECTIVE: To investigate whether the association between the maternal methylation status as reflected by low S-adenosylmethionine and high S-adenosylhomocysteine, is detrimental for cardiogenesis and congenital heart disease (CHD) in the offspring. METHODS: As part of a case-control study in the western part of the Netherlands, we evaluated 231 mothers of children with CHD and 315 control mothers of nonmalformed children. The total case group was analyzed and stratified into isolated (n=180) and nonisolated CHDs (n=51). The latter subgroup was further subdivided into Nonsyndromic (n=20), Down Syndrome (n=19), and Other Syndromes (n=12). A multivariable general linear model was used to test for differences between the case groups and controls. All analyses were adjusted for current B vitamin supplement use. RESULTS: Plasma total homocysteine was significantly different between the total case group (median, range 10.3, 4.0-43.8, P=.026) and the nonisolated cases (11.1, 5.5-43.8, P=.006) compared with the controls (10.0, 5.3-42.0). The subgroup of Down Syndrome presented significantly higher total homocysteine and S-adenosylhomocysteine levels and a lower S-adenosylmethionine/S-adenosylhomocysteine ratio than controls. CONCLUSION: Maternal hyperhomocysteinemia, and not hypomethylation, is a risk factor for having a child with CHD. Maternal hypomethylation, however, seems to be associated with offspring having CHD and Down syndrome. LEVEL OF EVIDENCE: II.

PMID: 18669723 [PubMed - as supplied by publisher]

Transient myeloproliferative disorder in a newborn with down syndrome.

Adv Neonatal Care. 2008 Aug;8(4):219-20

Authors:

PMID: 18690082 [PubMed - in process]

Transient myeloproliferative disorder in a newborn with down syndrome.

Adv Neonatal Care. 2008 Aug;8(4):208-18

Authors: Rhoderick JA, Bradshaw WT

This is the report of a newborn with Down syndrome diagnosed with transient myeloproliferative disorder (TMD) that required chemotherapy on the first day of life. Children with Down syndrome have a 10- to 20-fold increased risk of developing TMD. TMD is characterized by an uncontrolled proliferation of myeloblasts in the infant's peripheral blood and bone marrow. In most instances, this unique disorder has the ability to spontaneously "turn off" the overproliferation and enter a state of remission. Only supportive care is recommended for TMD during the first months of life unless the clinical condition requires intervention. As more cases of this baffling disorder are presented, it is important to share our experience to aid in management and diagnosis.

PMID: 18690081 [PubMed - in process]

Postcataract surgery outcome in a series of infants and children with Down syndrome.

Br J Ophthalmol. 2008 Aug;92(8):1112-6

Authors: Gardiner C, Lanigan B, O'Keefe M

AIMS: To report the visual and refractive outcome and complications in children with Down syndrome undergoing cataract extraction. METHODS: The case notes of 18 infants and children with lens opacities and Down syndrome who underwent cataract extraction between January 1981 and August 2006 were reviewed. RESULTS: Over the 25-year study period, 7% (33 eyes) of paediatric eyes undergoing cataract extraction had Down syndrome. The average follow-up time was 11.2 (SD 7.5) years with a range of 2.5 months to 25 years. 25 were congenital, and eight were developmental lens opacities. 40% of patients attained a postoperative BCVA between 6/9 and 6/18. There was a large myopic shift of -7.96 (4.7) D for aphakes and -8.06 (7.4) D for pseudophakes with an average increase in axial length of 3.58 (3.14) mm. There was a 30% incidence of posterior capsular opacification (PCO) overall, 38% in eyes without a primary posterior capsulotomy. Five eyes developed aphakic glaucoma, one eventually necessitating an enucleation. Two patients had retinal detachments on follow-up. CONCLUSION: Cataract extraction in our population of children with Down syndrome is a safe and effective procedure with a very encouraging visual outcome.

PMID: 18653605 [PubMed - in process]