1131

after treatment with chemotherapy including teniposide; none of the four children received radiotherapy. These cases appear to constitute a unique syndrome characterised by 11q23 chromosomal abnormalities, a short latent interval (1-6 years, median 3 years), and initial responsiveness of the second malignancy to induction treatment.1-s We observed two patients (one with NHL and the other with neuroblastoma) in whom AML developed 14 and 15 months after treatment with chemotherapy that included an epipodophyllotoxin; both had an 11q23 abnormality and responded to induction treatment. Although they have mutagenic (carcinogenic) potential6,’ the epipodophyllotoxins have a broad range of antineoplastic activity and have improved treatment outcome in patients with a variety of malignant neoplasms. The challenge now is to identify patients who are at especially high risk of therapy-related AML and factors that might increase the carcinogenic potential of the

epipodophyllotoxins. St Jude Children’s Research Hospital, Memphis, Tennessee 38101, USA, and Memphis College of Medicine, University of Tennessee

recurrence in the family would be underestimated. Once the molecular genetics of this condition is understood an easier, more reliable test should be developed.

Wessex

Regional Genetic Counselling Service, Department of Child Health, Southampton General Hospital, Southampton SO9 4XY, UK

I. K. TEMPLE

Department of Genetics, Hospitals for Sick Children, London

M. BARAITSER

Mothercare Department of Genetics, Institute of Child Health, London

M. E. PEMBREY

Department of Cytogentics, Queen Elizabeth Hospital, London

L. BUTLER

Wessex General

P.JACOBS

Genetics

Regional Laboratory, Hospital, Salisbury

Institute of Molecular Medicine, John Radcliffe Hospital, Oxford 1.

K. E. DAVIES

Oostra BA, Hupkes PE, Perdon LF, et al. New polymorphic DNA marker close to the fragile site FRAXA. Genomics 1990; 6: 129-32.

CHING-HON PUI

Chocolate and the auto-brewery syndrome L, Mott MG, Mann JR, et al. Second malignancies in children treated for non-Hodgkin’s lymphoma and T-cell leukaemia with the UKCCSG regimens. Br J Cancer 1987; 55: 463-66. 2. Pui C-H, Behm FG, Raimondi SC, et al. Secondary acute myeloid leukemia in children treated for acute lymphoid leukaemia. N Engl J Med 1989; 321: 136-42. 3. Ratain MJ, Kamier LS, Bitran JD, et al. Acute nonlymphocyric leukaemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung. Blood 1987; 70: 1412-17. 4. DeVore R, Whidock J, Hainsworth JD, et al. Therapy-related acute nonlymphocytic leukaemia with monocytic features and rearrangement of chromosome 1 1q. Ann Intern Med 1989; 110: 740-42. 5. Prieto F, Palau F, Badia L, et al. 11q23 abnormalities m children with acute nonlymphocytic leukaemia (M4-M5) associated with previous chemotherapy. Cancer Genet Cytogenet 1990; 45: 1-11. 6. Long BH, Musial ST, Brattain MG. Single- and double-strand DNA breakage and repair in human lung adenocarcinoma cells exposed to etoposide and teniposide. Cancer Res 1985; 45: 106-12. 7. DeMarini DM, Brock KH, Doerr CL, et al. Mutagenicity and clastogenicity of teniposide (VM-26) in L5178Y/TK +/--3.7.2C mouse lymphoma cells. Mutat Res 1987; 187: 141-49 1. Ingram

Unusual

presentation of fragile X syndrome referred for genetic

was

Mars BV, 5466AE Veghel, Netherlands

A.

VAN

LIESHOUT

counselling because their

SIR,-A family daughter, who was moderately developmentally delayed, was diagnosed as having the fragile X syndrome. In the daughter 28% fragile sites were demonstrated in a peripheral lymphocyte culture were

shocked to read on the front page of the Dutch De Telegraaf of Oct 5 that eating too much chocolate newspaper could cost a driver his licence. Under the heading "Dronken door chocolade" (drunk through chocolate) the newspaper cited a note in your Oct 6 issue (p 872). The same message was broadcast in a radio programme on the morning of Oct 5. The article in the Journal of Nutritional Medicine, on which your note was based, states that the 510 volunteers were patients attending for investigation of a variety of disorders and in whom chronic gut candidiasis or gut fermentation was already suspected clinically. Do you have evidence that this "auto-brewery syndrome" occurs in healthy people? If not, why did you not refer to the special character of the test group? It is most unfortunate that the linking of the test substance (glucose) with chocolate and the omission of the special character of the test group prompted a newspaper article likely to mislead the general public.

SIR,-I

and 16% in a repeat culture. Clinical examination of the child was incompatible with the diagnosis. The parents were concerned about their younger son. Early developmental milestones and speech were delayed. At age 3 years and 7 months his functional age was assessed as 2 years. On examination his head circumference was on the 29th centile and facial features were unremarkable but in keeping with the presumed diagnosis of fragile X syndrome. However, chromosome analysis showed that he had a normal male karyotype with no evidence of fragile sites. Two further separate lymphocyte cultures looking at over 100 cells at two different centres did not reveal fragile sites. His mother and father were of normal intelligence and had normal chromosomes. That the mother was a carrier was confirmed when her sister opted for prenatal diagnosis for fragile X. The male fetus proved to have 4-4% fragile sites, which confirmed that both women were obligate carriers of the condition. The family proved informative for the closely linked probe pRNl. This had been shown to have a 5% recombination rate with the disease locus.’ The results have shown that both the sister and her brother have inherited the same allele from their mother. The most obvious interpretation of these results is that the brother does have the fragile X syndrome, although fragile sites cannot be

demonstrated. There are few documented cases of this unusual finding, especially in a young retarded boy. This case should alert clinicians to the possibility that there are instances where fragile sites cannot

be demonstrated in an affected male. Such circumstances would be especially worrying in an isolated retarded male where the risk of

Fetal neural

graft survival

SiR,—The report by Dr Redmond and colleagues (Sept 29, p 820) of the post-mortem analysis of fetal neural grafts in a patient with end-stage parkinsonism is an important step in the evaluation of this procedure as a potential treatment. It is reassuring to learn that the grafts contained viable neurons which formed synapses. Nevertheless, the apparent absence of tyrosine-hydroxylase (THase) positive cells within the grafted tissue is disappointing, although many of the cells were reported to contain neuromelanin granules, suggesting that they might have been dopaminergic. The description by Redmond et al of the intracaudate mesencephalic grafts is, in some respects, reminiscent of the picture that can be found in the substantia nigra of patients with Parkinson’s disease. Thus, in the brains of parkinsonian patients, nigral cells have been found which contain neuromelanin but not THase and which have significantly lower levels of THase mRNA than control brains.1 The reduced levels of THase mRNA are not related to duration of disease, age, or levodopa therapy. However, the effect of disease severity is unknown.’A reduction of THase mRNA has also been found in the remaining nigral dopamine neurons of rats subjected to chronic 6-hydroxydopamine lesions.2 The reduction of THase mRNA in both of these situations may result from damage sustained during compensatory hyperactivity of surviving neurons.2,3 By analogy, one might speculate that the lack of THase immunoreactivity in the cells grafted to the parkinsonian brain reported by Redmond et al may also have resulted from cell damage following a period of compensatory metabolic hyperactivity. Another interesting finding which may support this possibility was the presence of neuromelanin in some grafted cells. Neuromelanin in human embryos (developing in situ) does not

Unusual presentation of fragile X syndrome.

1131 after treatment with chemotherapy including teniposide; none of the four children received radiotherapy. These cases appear to constitute a uniq...
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