An analysis of 190 pedigrees with Trisomy 21 suggests a cytoplasmic predisposition for the inheritance of Down syndrome and an association with other aneuploidies, non-chromosomal syndromes, autoimmune, neurodegenerative and oncological diseases.The extra chromosome seems to be responsible for the increase in free-radical intensity and the decrease of SOD-1 activity with age. The disturbance of the oxidant-antioxidant system could be the direct cause of this chromosomal nondisjunction. These data as well as the predominant maternal origin of the extra chromosome and the age-dependent incidence was the basis for the mtDNA sequencing in a donor of extra chromosome 21. Three new point, non-polymorphic mutations, not described before, were found in the following genes:- ATP-ase, G8764A and ND-5 G13243A with the same amino-acid substitutions Ala/Thr and in ND-1 G3337A-Val/Met. The mtDNA mutations detected in cases of Alzheimer's disease, insulin-independent diabetes, some cancers, and in somatically healthy people of 40 years and older could explain the connection of Down syndrome with these diseases and aging. Moreover, mtDNA analysis in patients with trisomy 21 might help to elucidate the nature of free-radical damage. This phenomenon is directly related to the manifestation of the syndrome and cannot be explained solely by the secondary SOD-1 gene dosage effect.
Arbuzova, S. (1998) Why it is necessary to study the role of mitochondrial genome in Trisomy 21 Pathogenesis. Down Syndrome Research and Practice, 5(3), 126-130.
Maroun, Heffernan, and Hallam
There is an ongoing effort to identify individual genes on Chromosome 21 that may independently each subserve one of the many diverse symptoms that constitute the Down syndrome. In contrast, the interferon system points to a multigene, multilocus, system distributed across Chromosome 21 that can explain each of the individual symptoms of the Down syndrome as a consequence of the concerted action of multiple genes which share in common a role in interferon action. To date, at least ten such genes have been identified on Chromosome 21. This number is likely to grow as new genes are identified, and their role in interferon action is uncovered. The recently discovered human SIM2 gene is presented here as an example. Its Intron 3 sequence reveals a clustering of interferon response elements that suggests an unexpected role for this gene in interferon action. We also present here a comparative analysis of the complex of untoward side effects of interferon therapy that reveals a striking similarity to the spectrum of symptoms that make up the Down syndrome. Taken together, these gene mapping and clinical observations suggest the possibility that the diverse symptoms of the Down syndrome could have a surprisingly non-diverse underlying biochemistry.
Maroun, Heffernan, and Hallam . (1998) The Untoward Side Effects of Interferon Therapy Correlate Well with the Spectrum of Symptoms that Make up the Down Syndrome. Down Syndrome Research and Practice, 5(3), 143-147.
Raffaele Ferri, Lilia Curzi-Dascalova, Stefano Del Gracco, Maurizio Elia, Salvatore Pettinato, and Sebastiano Musumeci
In this paper, research on sleep characteristics of subjects with Down syndrome is briefly reviewed and some new data on autonomic function during sleep are reported. Subjects with Down syndrome show a significant reduction in percentage of REM sleep (probably more evident in the most severely retarded subjects), a marked delay in first REM latency and a statistically significant decrease in high-frequency rapid eye movements during REM sleep. The percentage of REM sleep in humans can be considered as an index of brain "plasticity" and the high-frequency REMs can represent an index of the brain ability to organize information; thus, these studies have provided a neurophysiological basis to a psychopedagogical approach for the treatment of learning and memory disabilities in Down syndrome. Moreover, children with Down syndrome show a clearly decreased peak amplitude of growth hormone during sleep; this causes the poor physical development in these subjects and might be related to the occurrence of sleep apnea. Obstructive sleep apnea has also been repeatedly reported in these children; however, if obvious risk factors are absent, children with Down syndrome tend to show the presence of central sleep apnea which is caused by a probable dysfunction of autonomic control at a brainstem level.
Ferri, R, Curzi-Dascalova, L, Del Gracco, S, Elia, M, Pettinato, S, and Musumeci, S. (1998) Sleep Neurophysiopathology in Down syndrome. Down Syndrome Research and Practice, 5(3), 105-110.
Pinella Failla, Rosa Pettinato, Concetta Barone, and Corrado Romano
The Helicobacter pylorus (HP) is a Gram-negative bacterium that colonizes the antral portion of the stomach. It is the major aetiological agent responsible for chronic gastritis, gastric and duodenal ulcer disorders. This bacterium is widespread within the adult population (36.9%-53%), and the incidence of infection is positively correlated with age (6-20% in paediatric populations of Western Europe). The higher frequency among subjects with immunodeficiency and poor hygienic conditions has been pointed out. People with Down syndrome show higher susceptibility to this infection. The present study deals with the serological assay of IgG antibodies to HP in subjects with Down syndrome. We evaluated 77 subjects with Down syndrome, sex ratio M:F, 1:3, aged 1 to 40.7 years (mean 13.5). All were assayed for IgG antibodies to HP by the ELISA method. Subjects were separated into two groups according to age. The first group was made up of 46 subjects aged up to 14 years, and the second group contained 31 subjects over 14 years of age. Nine subjects (19.5%) in the first group and 16 subjects (51.6%) in the second group showed an antibody titre compatible with HP infection. The incidence in the whole sample of 77 subjects with Down syndrome was 32.4%. Therefore, people with Down syndrome do not seem to show a higher susceptibility to HP infection.
Failla, P, Pettinato, R, Barone, C, and Romano, C. (1998) Incidence of Helicobacter Pylori Antibodies in subjects with Down Syndrome. Down Syndrome Research and Practice, 5(3), 117-119.
Pinella Failla, Concetta Barone, Rosa Pettinato, and Corrado Romano
Cow's milk protein intolerance (CMPI) is the most frequent food intolerance in infancy. Its incidence ranges from 0.3 to 7.5%, according to different diagnostic criteria and clinical features. The diagnosis of CMPI is generally based on the level of IgG antibodies to beta lactoglobulin. An association of insulin-dependent diabetes mellitus (IDDM) with CMPI has been reported. CMPI in subjects with Down syndrome (DS) has been investigated by Nespoli et al. (1993) and Reichelt et al. (1994). We assayed IgG antibodies to beta-lactoglobulin, by the ELISA-method, in 78 subjects with Down syndrome and 97 mentally retarded and home-reared control subjects. Gastrointestinal disorders and IDDM was ruled out in both groups. Eleven (14.1%) and 5 (5.1%) subjects among Down syndrome group and control group respectively, were put on a CMP-free diet, and showed relief of symptoms and normalization of IgG antibodies after 6-21 months. In conclusion, CMPI appears to be more frequent in Down syndrome versus the control group and the specificity of IgG antibodies approaches 100% in our study.
Failla, P, Barone, C, Pettinato, R, and Romano, C. (1998) IGG Antibodies to Beta-Lactoglobulin and Cow's Milk Protein Intolerance in Down Syndrome. Down Syndrome Research and Practice, 5(3), 120-122.
Letizia Ragusa, Proto, Alberti, Corrado Romano, Rossodivita, and Colabucci
The authors examined IgF-1 plasma levels in 113 patients with Down Syndrome (DS) (68 males and 45 females, aged 1-23.66 years), all without severe congenital malformations, malnutrition, coeliac disease, alterations in thyroid or adrenal function, or taking any medication which might affect the study. The authors used a radioimmunoassay (RIA) method with plasma previously treated by acid-ethanol extraction and correlated the IgF-1 plasma levels with age and BMI (Body Mass Index) using multiple regression analysis. The BMI was higher in Down syndrome compared with normal subjects (NS), both in males (p=0.000006) and females (p= 0.034829). The two groups showed a positive correlation of IgF-1 levels with age. However, no correlation was found between IgF-1 levels and BMI.
Ragusa, L, Proto, Alberti, Romano, C, Rossodivita, and Colabucci. (1998) IGF-1 Levels in Down Syndrome. Down Syndrome Research and Practice, 5(3), 123-125.
Al Awadi, Naguib, Bastaki, Gouda, Mohammed, Abulhasan, Al-Ateeqi, and Krishna Murthy
Three young unrelated multiplex Kuwaiti families each confirmed to have 3 sibs with recurrent regular Trisomy 21 Down syndrome are reported. Chromosomal study of the parents showed normal karyotype for their mothers and two of their fathers (family II and III). These findings of multiplexes of regular Trisomy 21 patients resulted from the possibility of genetic predisposition for nondisjunction. Increased occurrence of Trisomy 21 in offspring of consanguineous marriages suggests that Trisomy 21 is etiologically heterogeneous and in a sub group of Trisomy 21 families nondisjunction may be genetically determined. In spite of extensive studies with regard to the origin of trisomy, the prime mechanism leading to recurrent Trisomy 21 or aneuploidy is not well understood. Genetic counselling of families with (maternal age <35 years), is a difficult task. Parental mosaicism, as well as "Genetic predisposition" should be considered in counselling families with sibships of regular trisomy-21.
Al Awadi, Naguib, Bastaki, Gouda, Mohammed, Abulhasan, Al-Ateeqi, and Krishna Murthy. (1998) Down Syndrome in Kuwait: Recurrent Familial Trisomy 21 in Siblings. Down Syndrome Research and Practice, 5(3), 131-137.
Rene Hugo, Brenda Louw, and Alta Kritzinger
Practical experience indicates a lack of clinical evaluation procedures for the evaluation of the listening behaviour of children with Down syndrome. This is especially important because these children are at risk for developmental communication delays concomitant to the high prevalence of recurrent otitis media and resultant auditory processing disorders. The aim of this study was to develop and then apply an evaluation procedure for listening behaviour to 10 children with Down syndrome. This scale was then evaluated in terms of its usefulness, by applying it to 56 children (younger than three years) attending an early intervention programme. Subsequently it was clinically used with 32 children with Down syndrome. It was found to be a useful and practical instrument for the assessment of listening behaviour.
Hugo, R, Louw, B, and Kritzinger, A. (1998) Development of a scale for the evaluation of listening behaviour of children with Down syndrome. Down Syndrome Research and Practice, 5(3), 138-142.
This study consists of a clinical and literature review of the special dental considerations unique to individuals with Down syndrome. The author is both a dentist and a parent of a child with Down syndrome. Physical and orofacial characteristics of Down syndrome are discussed including the teeth, gingiva, tongue, palate, and occlusion. Incidences of dental decay and periodontal disease are discussed and how best to treat these diseases in persons with Down syndrome. Most if not all persons with Down syndrome have some type of occlusal disharmony. Techniques to help prevent occlusal problems are discussed, including orthodontic therapy. Medical problems associated with Down syndrome that can affect dental treatment are discussed. Also, social and emotional factors involved in dental treatment are covered, including techniques to help children with Down syndrome become co-operative dental patients. Information on how to choose the right dentist for your child and how to communicate effectively with the dental staff is given. Finally, information on proper home care and prevention of dental disease is covered, including information on the most recent dental products.
Pilcher, E. (1998) Dental Care for the Patient with Down Syndrome. Down Syndrome Research and Practice, 5(3), 111-116.