Molecular characterization of tetralogy of fallot within Digeorge critical region of the chromosome 22.

The purpose of this study was to determine whether the levels of heterozygosity and microdeletion of specific loci within the DiGeorge critical region (del22q11) are associated with different phenotypes of tetralogy of Fallot (TF). Examinations were conducted on 84 sporadic TF patients and their unaffected parents for del22q11, using the following 9 simple tandem repeat polymorphic microsatellite markers: D22S420, D22S427, D22S941, D22S944, D22S264, D22S311, D22S425, D22S303, D22S257. The microdeletions were confirmed using quantitative PCR with markers TUPLE1, exon 2 of the UFD1L gene, and D22S264; the boundaries of these microdeletions were estimated using genotypic analyses of the unaffected family members. The del22q11 was identified in 14 patients (16.6%). The boundary of the shortest region of deletion overlap (SRO) in these 14 TF patients was identified, proximally using D22S427 and distally using the TUPLE 1 gene. The deletion of exon 2 of the UFD1L gene and TUPLE1 gene was identified in 13 patients (13/14 cases; 93%). The SRO in TF patients with del22q11 was at or close to the ADU breakpoint and centromeric to the UFD1L gene. The level of heterozygosity for the marker D22S944 in TF patients without del22q11 (n = 70) was found to be significantly lower than expected. Overall, this study demonstrated the significantly low level of heterozygosity within DiGeorge critical region in TF patients with or without del22q11. Our results suggest that the genetic factors leading to DiGeorge/velocardiofacial syndrome might also be partly responsible for TF phenotypes.

Clinical spectrum of Kawasaki disease in infants.

BACKGROUND: Kawasaki disease is a common acquired heart disease in children. Only a few reports have been published concerning Kawasaki disease in infants. This study was performed to assess the clinical spectrum of Kawasaki disease in infants. METHODS: Between January 1989 and December 1998, a total of 48 consecutive Kawasaki patients less than one year of age were enrolled and studied retrospectively. Coronary artery dilation was defined as the internal diameter of a coronary artery larger than 3 mm. All cases received 2 gm/Kg of intravenous immunoglobulin. We divided the patients into two groups; group I; coronary artery dilation (+) and group II; coronary artery dilation (-), and compared the clinical and laboratory data. RESULTS: Of 273 patients with Kawasaki disease, 48 (17.5%) were less than one year of age. Among these patients (< 1 year old), the median age was 7.8 +/- 2.8 months (range 2 months to 12 months), and the male to female ratio was 1.52:1. The incidence of atypical Kawasaki disease was 31.2% (compared with an incidence of atypical Kawasaki disease among patient more than one year of age of 7.5%; p < 0.001), and that of coronary artery dilation was 35.4%. Clinical manifestations included fever 100%, extremity change 91.6%, skin rash 89.6%, conjunctivitis 89.6%, oral mucosa change 89.6%, and cervical lymphadenopathy 0%. Laboratory data revealed white blood cell count: 15,403 +/- 6,282/mm3, hemoglobin: 10.1 +/- 1.0 gm/dl, neutrophil: 59.2 +/- 13.7%, lymphocytes: 30.6 +/- 13.1%, platelet count: 456,3000 +/- 216,4000/mm3, and C-reactive protein 8.2 +/- 5.6 mg/dl. Patients with coronary artery dilation had a longer duration of diagnosis, higher incidence of atypical presentation, lower incidence of conjunctivitis, lower incidence of skin rash, lower incidence of extremity change, and lower C-reactive protein. The predictive value of coronary artery dilation based on the combination of atypical presentation, duration of diagnosis, and C-reactive protein was 81.2%. CONCLUSIONS: Kawasaki disease in infants is associated with a high incidence of atypical presentation and increased risk of coronary artery dilation. We suggest that in an infant with insufficient diagnostic criteria for Kawasaki disease, care should be taken to avoid missing atypical Kawasaki disease. Echocardiography is an important tool for diagnosis of atypical Kawasaki disease.