Prenatal molecular diagnosis of a severe type of L1 syndrome (X-linked hydrocephalus).

OBJECT: The aim of this study was to evaluate the feasibility of prenatal L1CAM gene testing for X-linked hydrocephalus (XLH). METHODS: In a nationwide study conducted in Japan between 1999 and 2009, the authors identified 51 different L1CAM gene mutations in 56 families with XLH. Of these 56 families, 9 obligate carriers requested prenatal gene mutation analysis for the fetal L1CAM gene in 14 pregnancies. RESULTS: In 2004, new clinical guidelines for genetic testing were established by 10 Japanese genetic medicine-related societies. These guidelines stated that the genetic testing of carriers should be done only with their consent and with genetic counseling. Therefore, because females are carriers, since 2004, L1CAM gene analysis has not been performed for female fetuses. The authors report on 7 fetal genetic analyses that were performed at the request of families carrying L1CAM mutations, involving 3 female (prior to 2004) and 4 male fetuses. Of the 7 fetuses, 3 (1 male and 2 female) carried L1CAM mutations. Of these 3, 1 pregnancy (the male fetus) was terminated; in the other cases, the pregnancies continued, and 3 female and 3 male babies without the XLH phenotype were born. CONCLUSIONS: Prenatal L1CAM gene testing combined with genetic counseling was beneficial for families carrying L1CAM mutations.

Cigarette smoking and glutathione S-transferase M1 polymorphism associated with risk for uterine cervical cancer.

AIM: To elucidate the role of tobacco smoking and polymorphisms of carcinogen metabolism genes in cervical carcinogenesis. METHODS: We analyzed genotypes of nine genes, 11 polymorphisms encoding carcinogen metabolizing enzymes, information on smoking, and the presence of human papillomavirus in 124 Japanese cervical cancer patients and 125 healthy controls. RESULTS: The incidence of human papillomavirus infection (95.5% vs 9.9%; P < 0.001; odds ratio (OR), 231.98; 95% confidence interval [CI], 57.17-941.22), and smoking (41.1% vs 18.4%; P < 0.001; OR, 3.40; 95% CI, 1.88-6.17) were both significantly higher in patients than in controls. The genotype distributions of CYP1A1, CYP2E1, CYP2A6, NQO1, NAT2, mEH, MPO and GSTT1 genes were not statistically different; however, the ratio of the GSTM1 null genotype was significantly higher in patients than in controls (62.1% vs 47.2%; P = 0.019; OR, 1.83; 95% CI, 1.11-3.04). The incidence of GSTM1 null was significantly higher in the non-smoking group (63.0% vs 47.1%; P = 0.038; OR, 1.92; 95% CI, 1.04-3.54), and not in the smoking group (60.8% vs 47.8%; P = 0.300; OR, 1.69; 95% CI, 0.63-4.56). CONCLUSIONS: In the current study, risk factors for developing cervical cancer were tobacco smoking and GSTM1 null; however, no association was observed between these two factors. We could not prove that smoking-GSTM1 null interaction was responsible for the increase in cervical cancer among young Japanese, and further studies with more detailed smoking status, not only active but passive smoking, will be required.

Four cases of fetal hypoechoic hepatomegaly associated with Trisomy 21 and transient abnormal myelopoiesis.

OBJECTIVE: Our objective was to determine the clinical significance of fetal hypoechoic hepatomegaly and serial change of liver sizes. METHODS: The liver sizes of four fetuses with hypoechoic hepatomegaly were serially estimated by liver length, as measured from the dome of the right hemidiaphragm to the tip of the right lobe. RESULTS: All cases were associated with trisomy 21 or transient abnormal myelopoiesis (TAM). Two cases were trisomy 21 with TAM, one case was a phenotypically normal newborn, who had developed TAM during the fetal period, and the last case was trisomy 21 without TAM. In the last case, it is speculated that TAM had developed and regressed completely before birth. Two cases, whose hepatomegaly had improved before birth, showed good prognosis and the other two cases, in whom improvement had not been observed, resulted in death after birth by liver failure. CONCLUSION: These experiences show that one of the differential diagnoses of hypoechoic hepatosplenomegaly is TAM and that the change of live size is a predictor of prognosis.

Multiple brown tumors in primary hyperparathyroidism caused by an adenoma mimicking metastatic bone disease with false positive results on computed tomography and Tc-99m sestamibi imaging: MR findings.

We encountered an unusual case of hyperparathyroidism with both hemosiderin deposits on the ribs and low intensity on T2-weighted magnetic resonance imaging (MRI) caused by a parathyroid adenoma with multiple brown tumors that mimicked metastatic bone tumor due to false positive results on computed tomography (CT) and Tc-99m sestamibi (MIBI) imaging. The patient, a middle-aged woman, had very high serum levels of calcium (14.1 mg/dl), alkaline phosphatase (9,369 IU/l) and intact-PTH (12,400 pg/ml), and a large tumor (2.5 cm in diameter) in the lower portion of the left lobe of the thyroid. Plain X-ray revealed a soft tumor in the left chest wall. On CT scan, there were multiple destructive masses in the ribs, including large intramedullary masses on both 3rd ribs. On MIBI scintigraphy, there was strong late uptake in the lower portion of the left cervical region, both 3rd ribs, and the left 7th, 8th, and 10th ribs. T2-weighted image MRI scans showed that both 3rd ribs had a low intensity with hemosiderin deposits. These findings suggested that the patient had hyperparathyroidism with multiple bone metastases due to carcinoma of the parathyroid gland. However, on pathology, the resected tumor of lower portion of the left lobe of thyroid was diagnosed as a parathyroid adenoma, and the tumors of the left 3rd and 7th ribs, as well as the right 2nd rib, were shown to be brown tumors. After resection, the patient's serum levels of calcium, alkaline phosphatase, and intact-PTH normalized. At 1.5-years follow-up, CT, MIBI, and MRI scans showed no abnormal findings. It is necessary to determine whether MRI can be used to distinguish between brown tumors and metastases caused by carcinoma of the parathyroid gland.