Phenotype-genotype correlation in a patient with co-occurrence of Marfan and LEOPARD syndromes.

Here we report on a patient with multiple lentigines, hypertelorism, short stature, arachnodactyly, scoliosis, dissecting aneurysm, hypertrophic cardiomyopathy and developmental delay, and a family history of Marfan syndrome. The patient is affected with both Marfan and LEOPARD syndromes. Mutational screening of the FBN1 gene showed a c.1464T>A (p.C488X) mutation and screening of the PTPN11 gene showed a c.836A>G (p.Y279C) mutation. We conclude that each mutation contributed independently to individual features in the ocular and cardiovascular systems, although short stature was more significantly influenced by the p.Y279C change in PTPN11 rather than the mutation in FBN1. To our knowledge, this is the first report of mutations in both FBN1 and PTPN11 with combined phenotypes of Marfan and LEOPARD syndromes.

IVIG reduced vascular oxidative stress in patients with Kawasaki disease.

BACKGROUND: Oxidative stress (OS) contributes to the acute phase of Kawasaki disease (KD) in a manner that is as yet unknown. In the present study OS in the acute phase of KD was investigated by measuring urinary 8-iso-prostaglandin F2alpha (8-iso-PG) and evaluating its correlation to the efficacy of intravenous immunoglobulin (IVIG) administration. METHODS AND RESULTS: The 62 patients with acute phase of KD were enrolled, as well as 20 healthy children (HC) and 20 with acute febrile illness (FI). Urinary samples were obtained before and after administration of IVIG. The HC and FI groups also had inflammatory markers evaluated at the same time. The 8-iso-PG was significantly elevated in the 62 KD patients (719 +/-335 pg/mg Cr) without IVIG administration compared with those with FI (583 +/-213 pg/mg Cr) as well as HC (443 +/-288 pg/mg Cr) (P<0.01). 40 patients were given 3 different regimens of IVIG: 16 received 2 g/kg for 1 day; 17 received 1 g/kg for 1 day; 7 received 400 mg . kg(-1) . day(-1) for 5 days. All regimens of IVIG reduced the 8-iso-PG level at 7 days after initiation. CONCLUSIONS: OS provokes vasculitis in KD, the activation of which was reduced by IVIG. The urinary level of 8-iso-PG is a useful marker of the effectiveness of IVIG in the acute phase of KD.

Efficacy and limitations of continuous intravenous epoprostenol therapy for idiopathic pulmonary arterial hypertension in Japanese children.

BACKGROUND: There is little data on the long-term effects of continuous intravenous epoprostenol for children with idiopathic pulmonary arterial hypertension (IPAH) in Japan. METHODS AND RESULTS: Thirty-one IPAH patients younger than 18 years old who had begun epoprostenol therapy at Toho University Omori Medical Center between January 1999 and June 2004 were reviewed. During a mean follow up of 3.4 years, the rate of those who survived or did not undergo a lung transplantation among the 27 patients who received home infusion therapy of epoprostenol was 100% at 1 year, 96.3% at 2 years, and 79.4% at 3 years. In 82% of survivors, the World Health Organization functional class was changed from III or IV to II according to improvements in the plasma brain natriuretic peptide level and the distance walked in 6 min during the follow-up period. In most cases, mean pulmonary artery pressure and the ratio of pulmonary to systemic vascular resistance remained high, although the cardiac index had improved to within a normal range 1 year after the initiation of epoprostenol. Therefore, sildenafil was administered as an additional therapy to 16 patients who presented with sustained severe PAH. CONCLUSIONS: Continuous IV epoprostenol certainly improves survival and exercise tolerance in childhood IPAH, although the improvement of pulmonary vascular resistance regardless of long-term epoprostenol therapy is insufficient. Therefore, the addition of a new drug, such as sildenafil, is recommended to be administered in adjunction with epoprostenol.