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association of hyperglycaemia with normal insulin is shown only in severe forms of NIDDM, with fasting plasma glucose usually higher than 12 mmol/l.2 This is clearly not so in our patients. Second, during euglycaemic clamps, the endogenous insulin secretion was suppressed in MODY patients but not in controls, with plasma glucose concentrations of 4-9 mmol/1, indicating that in these patients the set point for insulin secretion is indeed higher than in controls. Third, this higher set point was confirmed in vitro, after transfection of Escherichia coli with mutant GCK alleles (Jain et al,
unpublished). Lastly, we agree with Page and colleagues that, in individuals, it might not always be possible to differentiate between MODY and NIDDM by different insulin responses to glucose. However, simple clinical data such as the age of onset of diabetes or the pattern of inheritance within the kindred may help considerably. After all, that is how MODY has been diagnosed until now. Centre D’etude du Polymorphisme Humain, 27 rue Juliette Dodu, 75010 Paris, France
GILBERTO VELHO KARINE CLÉMENT MARIA E. PUEYO PHILIPPE FROGUEL
Hattersley AT, Turner RC, Permutt MA, et al. Linkage of type-2 diabetes to the glucokinase gene. Lancet 1992; 339: 1307-10. 2. DeFronzo RA, Ferrannini E, Simonson DC. Fasting hyperglycemia in non insulin dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake. Metabolism 1989; 38: 387-95. 1.
(figure). Both families opted for terminations, and the lesions were confirmed
at
necropsy.
Although there is no strict correlation between MRI findings and the neurological outcome of affected fetuses, the risk of severe mental retardation may be greater when multiple subependymal lesions and subcortical tubers occur.4 Our two cases confirm that the anatomical brain lesions of tuberous sclerosis can be detected at 33 weeks of amenorrhoea. It will be important to determine whether or not they are visible at 22/24 weeks, the earliest time at which cardiac rhabdomyomas have been described.5 VERONIQUE MIRLESSE HERON WENER FRANCOIS JACQUEMARD Medicine and Fetal Biology Service, CHANTALE PEROTEZ Institute de Puericulture, 75014 Paris, France FERNAND DAFFOS Radiopaediatrics Service, Hôpital Necker-Enfants Malades, Paris
PASCALE SONIGO FLORENCE BRUNELLE
1. Dawson MH. Tuberous sclerosis. J La State Med Soc 1990; 142: 35-38. 2. Journel H, Roussey M, Plais MH, Milon J, Almange C, Le Marec B. Prenatal
3. 4. 5.
diagnosis of familial tuberous sclerosis following detection of cardiac rhabdomyoma by ultrasound. Prenat Diagn 1986; 6: 283-89. Mattison DR, Angtuaco T. Magnetic resonance imaging in prenatal diagnosis. Clin Obstet Gynecol 1988; 31: 370-81. Inoue Y, Nakajima S, Fukuda T, et al. Magnetic resonance imaging of tuberous sclerosis. Neuroradiology 1988; 30: 379-84. Crawford DC, Garrett C, Tynan M, Neville BG, Allan LD. Cardiac rhabdomyomata as a marker for the antenatal detection of tuberous sclerosis. J Med Genetics 1983; 20: 303-12.
Magnetic resonance imaging in antenatal diagnosis of tuberous sclerosis SIR,- Tuberous sclerosis is an autosomal dominant disease with variable expression, in which almost 80% of cases are thought to be due to de-novo mutations.1 Patients have widely varying degrees of mental retardation, frequently with early and severe epileptic attacks. Antenatal diagnosis of tuberous sclerosis in the absence of a family history has been based on ultrasonographic detection of multiple cardiac rhabdomyomas which, in 15-80% of cases, are associated with the disease.2 Anatomical brain abnormalities, although present in 70% of cases, are undetectable by ultrasonography. Progress in antenatal magnetic resonance imaging (MRI), which does not affect the fetus,3 means that a firm diagnosis of tuberous sclerosis
can
be made in utero.
MRI in fetus with tuberous sclerosis. 1
= penventncular subependymal nodule,
2= cortical tuber
Two patients were referred to our unit for investigation of cardiac rhabdomyomas detected by routine ultrasonography at a late stage of pregnancy (33 weeks’ amenorrhoea). Because family studies, especially of the skin, revealed no signs or history of tuberous sclerosis, fetal MRI was done after maternal premedication with flunitrazepam to immobilise the fetus. Multiple T1-weighted sequences (TR 340 ms, TE 6 ms) with a surface antenna revealed hyperdense periventricular subependymal nodules and typical cortical tubers
multiple
Cardiac
pacing
and breast carcinoma
SIR,- There is no evidence that the siting of pacemaker boxes in the chest-wall affects the development or behaviour of synchronous ipsilateral breast carcinoma. However, close proximity of a pacemaker box may complicate the management of breast carcinoma. We report two cases in which a breast carcinoma was found adjacent to a recently inserted pacemaker box. The first case was a 39-year-old woman who presented with episodes of paroxysmal tachycardia refractory to medical treatment. She underwent elective pacing, the box being sited in the upper outer quadrant of the left chest-wall anteriorly. A week later, she presented with a 2 x 1 cm, clinically malignant mass 3 cm from the box. Investigation confirmed an infiltrating intraductal breast carcinoma, which was removed by wide excision. She was then referred back to the regional pacing centre for repositioning of the pacemaker, enabling her to undergo chest-wall radiotherapy. The second case was a 72-year-old woman who underwent elective pacing for recurrent syncope due to sick sinus syndrome. 3 weeks later, she presented with a 3 x 2 cm mass 3 cm from the pacing box. Tissue core biopsy confirmed breast carcinoma, and wide local excision was done. The margin of excision reached the inferior border of the pacemaker pocket. The patient subsequently had the box resited, followed by chest-wall radiotherapy. Although it is unlikely that the prognosis of either patient was adversely affected by the positioning of the pacemaker box, the management of the subsequently detected carcinomas was more complex. In both cases, clinical examination and mammography would probably have led to detection of the tumour before elective siting of the pacemaker. Because most female patients requiring cardiac pacing are postmenopausal (with incidence rates of breast carcinoma of 191 9 and 295.3per 100 000 at ages 70 and 85, respectively), we suggest that breast examination and mammography are routine before elective pacing is undertaken in women.2,3 Department of Surgery, Kent and Canterbury Hospital, Canterbury CT1 3NG, UK
J. COMMINS S. C. A. FRASER R. M. HEDDLE
D.
1. Dalal JJ, Winterbottam T, West RR, Henderson AH. Implanted pacemakers and breast carcinoma Lancet 1980; u: 311. 2 Waterhouse JAH. Cancer handbook of epidemiology and prognosis. Edinburgh: Churchill Livingstone, 1974. 3. Cancer Statistics Registration for England and Wales for 1986. London: HM Stationery Office, 1991.