Research in the Etiology of Down's Syndrome Intricacies and Pitfalls

Cytological studies have shown that Down's syndrome (“ mongolism ”) is the result of a chromosomal anomaly which occurs either in one of the parent's germ cells or at a very early stage in (embryonic) development of the affected individual. The chromosomal anomaly involves the occurrence of a third number 21 chromosome, in addition to the normal complement of two, either separately (i. e., trisomy-21) or attached to one of the other acrocentric chromosomes (i. e., translocation to one of the chromosomes numbered 13-15 or 22 — Denver Report, 1960). Epidemiological studies have indicated that numerous factors are related to, and may affect, incidence of the chromosomal anomalies resulting in Down's syndrome. Studies by Collmann and Stoller (1962a, b) imply fluctuations of annual incidence with a 5-6 year periodicity, a higher incidence in urban compared to rural areas and a clusteting of affected births in certain geographic regions. Collmann and Stoller postulated an “ infectious agent, probably a virus ”, to account for their data. No connection, however, can yet be drawn between such a hypothesis and the established cytogenetic anomaly. Periodic fluctuations in incidence, which are characteristic of recurrent epidemics (Gordon, 1962), have also been reported for congenital anomalies other than Down's syndrome, such as anencephaly, spina bifida, and hydrocephaly (Collmann and Stoller, 1962b; Guthkelch, 1962; Alter, 1962; Slater, Watson and McDonald, 1964).

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Effects of Speech and Speech and Sign Instruction on Oral Language Learning and Generalization of Action + Object Combinations by Down's Syndrome Children

Journal of Speech and Hearing Disorders ◽

10.1044/jshd.4903.293 ◽

1984 ◽

Vol 49 (3) ◽

pp. 293-302 ◽

Cited By ~ 31

Author(s):

Mary Ann Romski ◽

Kenneth F. Ruder

Keyword(s):

Language Learning ◽

Oral Language ◽

Early Stage ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Treatment Conditions ◽

Linguistic System ◽

Object Relational ◽

Sign Conditions ◽

Level Performance

This study was designed to compare the effects of speech and speech-plus-sign stimulation during comprehension treatment on the oral language learning and generalization of action + object relational meanings. Ten home-reared Down's syndrome children in Early Stage I received concurrent comprehension treatment in Speech and Speech-Sign conditions using a miniature linguistic system. Upon attainment of criterion level performance in both conditions, generalization tasks were administered to measure the effects of the comprehension treatment on the comprehension and the production of treated and untreated action + object combinations. The results obtained from this study indicated that the two treatment conditions did not differ significantly for either learning or generalization. The data did, however, indicate that individual patterns of acquisition were evident among the children. Caution is advised concerning the automatic adoption or rejection of manual sign as part of oral language intervention programs.

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Cast aside

10.1093/med/9780198854807.003.0027 ◽

2021 ◽

pp. 191-196

Author(s):

Michael Obladen

Keyword(s):

Trisomy 21 ◽

Homo Sapiens ◽

Down's Syndrome ◽

Scientific Progress ◽

Down’S Syndrome ◽

Chromosomal Anomalies ◽

Additional Chromosome ◽

Ethnic Classification ◽

The Right ◽

Invasive Techniques

Trisomy 21 originated with Homo sapiens, or even before, as it exists in other primates. However, in antiquity, Down’s syndrome was rare: mothers were younger, and children failed to reach adulthood. For centuries, trisomy 21 and hypothyreosis were confused. Scientific reports originated from asylums for the mentally retarded. In 1866, John Langdon Down at Earlswood published a description of symptoms in his ‘Ethnic classification of idiots’ and coined the term ‘Mongolian’. Jerôme Lejeune identified an additional chromosome 21 causing the disorder. Maternal age rose markedly for various reasons, as did the prevalence of trisomy 21. From 1968, high-risk pregnancies were screened and interrupted because of Down’s syndrome. Non-invasive techniques now enable all pregnancies to be screened to detect chromosomal anomalies early and precisely. The topic is hotly debated and consensus unlikely. Legislation will not halt scientific progress, but it should ensure that in the same society contradictory attitudes can be held and mutually respected: the right to accept a disabled infant and the right not to accept it.

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Monitoring Trends in Prenatal Diagnosis of Down's Syndrome in England and Wales, 1989–92

Journal of Medical Screening ◽

10.1177/096914139400100410 ◽

1994 ◽

Vol 1 (4) ◽

pp. 233-237 ◽

Cited By ~ 6

Author(s):

Joan K Morris ◽

David E Mutton ◽

Roy Ide ◽

Eva Alberman ◽

Martin Bobrow

Keyword(s):

Prenatal Diagnosis ◽

Confidence Interval ◽

Regional Differences ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Fold Increase ◽

Maternal Serum ◽

Serum Analysis ◽

Chromosomal Anomalies ◽

England And Wales

The national register of chromosomal anomalies that lead to Down's syndrome has enabled the monitoring of change in prenatal diagnosis for this condition, and the factors which affect the change. The proportion of cases of cytogenetically diagnosed Down's syndrome in England and Wales detected prenatally rose to 46% in 1991–2 from 31% in 1988–9, a 1·5-fold increase (95% confidence interval 1·3 to 1·7). The increase was confined to mothers under 40 years and was due to the introduction of screening by maternal serum analysis and ultrasound. Over a quarter of affected pregnancies in women aged 25–29 were detected prenatally in 1991–2 compared with less than 10% in 1988–9. Analysis of the data showed regional differences in prenatal diagnosis rates, and in the length of time elapsing between the diagnostic test and termination of an affected pregnancy. An inexplicable finding was that this period varied with the sex of the fetus, being on average a day longer for females than for males.

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Birth Order and Maternal Age of Psychiatric In-patients

The British Journal of Psychiatry ◽

10.1192/bjp.112.492.1131 ◽

1966 ◽

Vol 112 (492) ◽

pp. 1131-1141 ◽

Cited By ~ 21

Author(s):

Ming-Tso Tsuang

Keyword(s):

Environmental Factors ◽

Birth Order ◽

Maternal Age ◽

Chromosomal Abnormalities ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Chromosomal Anomaly ◽

Average Population ◽

Departure From Normality

Light may be thrown on the aetiology of human abnormalities by studying the position in birth order occupied by affected individuals and the age of the mother at the time of their birth. There should be no shift from average population values in either of these respects in the case of conditions directly and solely due to an abnormal gene, though there may be such a shift in conditions due to chromosomal abnormalities, such as mongolism (Down's syndrome). If, however, the question of a chromosomal anomaly does not arise, then departure from normality in birth order and maternal age suggest that environmental factors are involved in the causation of the condition.

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Chromosome abnormalities in Down's syndrome patients with acute leukemia

Blood ◽

10.1182/blood.v58.3.459.bloodjournal583459 ◽

1981 ◽

Vol 58 (3) ◽

pp. 459-466 ◽

Cited By ~ 1

Author(s):

Y Kaneko ◽

JD Rowley ◽

D Variakojis ◽

RR Chilcote ◽

JW Moohr ◽

...

Keyword(s):

Acute Leukemia ◽

Early Stage ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Giemsa Stain ◽

Chromosome Abnormalities ◽

Leukemic Cells ◽

Myeloid Differentiation ◽

Acute Nonlymphocytic Leukemia ◽

Blast Cells

Chromosome and cytologic studies were performed on three Down's syndrome (DS) patients with acute nonlymphocytic leukemia (ANLL). All three patients had an aneuploid clone in their leukemic cells: 50, XX, +6, +19, +21, +22, +8, XX, +21, and 47,XY, +8, - 21 +dic(21;21)(p13;p11). Every patient appeared to have acute undifferentiated leukemia when the blast cells were examined with Wright-Giemsa stain; cytochemistry studies, however, showed that the leukemic blasts were in an early stage of myeloid differentiation. The two patients with +8 had a preleukemic phase; the blast cells of the patient with an extra no. 19 and no.22 could not be differentiated morphologically from those of the two patients with an extra no. 8. Our findings and a review of data on 40 other patients suggest that most DS children with ANLL have hyperdiploidy, which is usually related to gains of C, F, and /or G chromosomes, and that the abnormalities of +8 and of +19, +22 in DS children may be associated with acute leukemia (AL) in an early stage of myeloid differentiation.

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Chromosome abnormalities in Down's syndrome patients with acute leukemia

Blood ◽

10.1182/blood.v58.3.459.459 ◽

1981 ◽

Vol 58 (3) ◽

pp. 459-466 ◽

Cited By ~ 52

Author(s):

Y Kaneko ◽

JD Rowley ◽

D Variakojis ◽

RR Chilcote ◽

JW Moohr ◽

...

Keyword(s):

Acute Leukemia ◽

Early Stage ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Giemsa Stain ◽

Chromosome Abnormalities ◽

Leukemic Cells ◽

Myeloid Differentiation ◽

Acute Nonlymphocytic Leukemia ◽

Blast Cells

Abstract Chromosome and cytologic studies were performed on three Down's syndrome (DS) patients with acute nonlymphocytic leukemia (ANLL). All three patients had an aneuploid clone in their leukemic cells: 50, XX, +6, +19, +21, +22, +8, XX, +21, and 47,XY, +8, - 21 +dic(21;21)(p13;p11). Every patient appeared to have acute undifferentiated leukemia when the blast cells were examined with Wright-Giemsa stain; cytochemistry studies, however, showed that the leukemic blasts were in an early stage of myeloid differentiation. The two patients with +8 had a preleukemic phase; the blast cells of the patient with an extra no. 19 and no.22 could not be differentiated morphologically from those of the two patients with an extra no. 8. Our findings and a review of data on 40 other patients suggest that most DS children with ANLL have hyperdiploidy, which is usually related to gains of C, F, and /or G chromosomes, and that the abnormalities of +8 and of +19, +22 in DS children may be associated with acute leukemia (AL) in an early stage of myeloid differentiation.

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Atypicality or Specific Screen: Which is Better at Detecting Non-Down's Chromosomal Anomalies?

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329703400613 ◽

1997 ◽

Vol 34 (6) ◽

pp. 675-680 ◽

Cited By ~ 2

Author(s):

T M Reynolds

Keyword(s):

Chromosomal Abnormalities ◽

Screening Program ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Chromosome Abnormalities ◽

Trisomy 18 ◽

Trisomy 13 ◽

Screening Tests ◽

Chromosomal Anomalies ◽

Screening Programs

I evaluated the value of adding a trisomy 18 screen to routine Down's screening and compared it with the benefits of atypicality screening. I studied 5080 unaffected pregnancies, 144 Down's syndrome and 190 non-Down's syndrome chromosome abnormalities (20 trisomy 13; 79 trisomy 18; 20 Turner's syndrome; 29 other sex chromosome abnormalities; 8 triploidy; and 34 miscellaneous). Using a one in 250 cut off, the Down's screen gave a screen positive rate of 4·07%; addition of atypicality without a trisomy 18 screen gave an extra 0·9% screen positives; trisomy 18 screening without atypicality gave an extra 0·51% screen positives; and atypicality screening after trisomy 18 screening gave 0·52% screen positives. Total screen positive rates were: Down's screening only, 4·07%; Down's screening + atypicality, 4·97%; Down's screening + trisomy 18 screen, 4·58%; Down's screening + trisomy 18 screen + atypicality, 5·09%. The detection rate for Down's syndrome using a one in 250 cut off was 58·9% and with addition of trisomy 18 and atypicality screening this increased to 59·3%, indicating that the extra screens add little to detection of Down's syndrome. For the other chromosomal abnormalities, Down's screening alone detected 22·6% of cases overall and addition of trisomy 18 and atypicality screening increased this to 49%. Examination of the marginal benefits of the extra screening tests revealed that the trisomy 18 screen was better at detecting chromosomal abnormalities than the Down's screen and that it would, therefore, be worthwhile adding this to all screening programs. Atypicality proved to be much less effective and it is suggested that this screen should only be applied in the early days of a screening program until sufficient data is available to design specific screens.

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