Phelan-McDermid Syndrome in Pediatric Patients With Novel Mutations: Genetic and Phenotypic Analyses.

Background: PhelanrMcDermid syndrome (PMS) is an uncommon autosomal dominant inherited developmental disorder. The main characteristics are hypotonia, intellectual disability, autism spectrum disorder, autism-like behaviors and tiny facial deformities. Most cases are caused by the deletion of the 22q13 genomic region, including the deletion of SHANK3. Methods: Genetic and phenotype evaluations of ten Chinese pediatric patients were performed. The clinical phenotypes and genetic testing results were collected statistically. We analyzed the deletion of the 22q13 genomic region and small mutations in SHANK3 (GRCh37/hg19) and performed parental genotype verification to determine whether it was related to the parents or was a novel mutation. Results: The age of the patients diagnosed with PMS ranged from 0 to 12 years old. Nine of the pediatric patients experienced Intellectual Disability, language motion development delay and hypotonia as prominent clinical features. One subject had autism, two subjects had abnormal electroencephalogram discharge and one subject was aborted after fetal diagnosis. Three patients had a SHANK3 mutation or deletion. All but the aborted fetuses had intellectual disability. Among the ten patients, a deletion in the 22q13 region occurred in seven patients, with the smallest being 60.6 kb and the largest being >5.5 Mb. Three patients had heterozygous mutations in the SHANK3 gene. Conclusion: All ten patients had novel mutations, and three of these were missense or frameshift mutations. For the first time reported, it is predicted that the amino acid termination code may appear before protein synthesis. The novel mutations we discovered provide a reference for clinical research and the diagnosis of PMS.

[Association between SCN1A rs3812718 polymorphism and generalized epilepsy with febrile seizures plus].

OBJECTIVE: To investigate the association between SCN1A rs3812718 polymorphism and generalized epilepsy with febrile seizures plus (GEFS+), and to provide potential molecular targets for the diagnosis and treatment of GEFS+. METHODS: The iPLEX technique in the MassARRAY system was used to determine SCN1A rs3812718 polymorphism, genotype frequency, and allele frequency in 50 patients with GEFS+ and 50 healthy controls. RESULTS: As for the frequencies of CC, CT, and TT genotypes in SCN1A rs3812718, there was a significant difference in the frequency of TT genotype between the GEFS+ group and the control group (P<0.05). There was also a significant difference in the frequency of T allele between the two groups (P<0.05). Compared with those carrying CC genotype or C allele, the individuals with CT genotype , TT genotype or T allele had a higher risk of developing GEFS+ (CT/CC: OR=4.05, 95%CI: 1.04-15.69; TT/CC: OR=30.60, 95%CI: 6.46-144.85; T/C: OR=4.64, 95%CI: 2.54-8.48). CONCLUSIONS: SCN1A rs3812718 polymorphism is a risk factor for GEFS+, and the population carrying T allele may have an increased risk of GEFS.

[Critical care and therapy based different illness state of 80 patients with severe hand-foot-and-mouth disease seen in Shenzhen].

OBJECTIVE: To discuss the treatment strategy of severe hand-foot-and-mouth disease (HFMD) cases, prevent the severe cases from progressing to fatal condition and enhance the survival rate of critically ill patients. METHODS: Eighty HFMD cases were divided into four groups, A, B, C and D, according to the severity of patients' nervous system manifestation and other system involved. Different intensive care and treatments were used and the effect and outcome were analyzed for each group. All statistical analyses were performed by using SPSS software 13.0. One-way ANOVA and Chi-square test were used for data analysis. RESULTS: The most common symptoms were continuous fever (69/70) and myoclonic jerk (67/70). The fewer the rashes were, the more severe the patient's condition was, heart rate >200/min, hypertension, increase of white blood cells in peripheral blood and hyperglycemia were common in patients with lesions in brain stem and pulmonary edema. There were no relations between patient's conditions and CSF white blood cells and CRP. CNS involvement was highly associated with EV71 infection. There were 69 cases in group A, B and C in total and all recovered. Of 11 patients in group D, 6 got complicated neurogenic pulmonary edema and circulatory failure, 2 cases died and 9 cases survived, 8 cases recovered without sequelae while one case had sequelae of mental retardation and dyscinesia. CONCLUSION: Administration of mannitol, methylprednisolone, IVIG and other supportive treatments in time and reasonably might have advantages in avoiding aggravation of the condition and enhancing the rate of successful rescue in patients with nervous system involvement.

[Changes of immune function in patients with enterovirus 71 infection].

OBJECTIVE: To investigate the association of changes in immune function with enterovirus 71 (EV71) cases with different severity of the disease. METHOD: Forty-six EV71-infected patients and 12 age-matched healthy children were enrolled in this study. The patients were divided into four groups according to critical degree of enterovirus 71 infection: hand-foot-and-mouth disease (HFMD); central nervous system disease (CNSD); autonomic nervous system dysregulation (ANSD) and pulmonary edema (PE). We analyzed CD14+ monocyte HLA-DR expression, lymphocyte immunophenotypes, the proportion of CD4+CD25+ Foxp3high regulatory T cells (Treg cells) and Th17 cells, cytokines (IL-1beta, TNF-alpha, IL-10, TGF-beta, IL-6, IL-17A), evaluated the mRNA levels of Foxp3 and ROR-gammat, and serum immunoglobulin and complements. RESULT: (1) Serum concentrations of IL-1beta and TNF-alpha elevated in mild cases, while declined in severe cases, and were lower in PE group (P<0.05). Serum concentrations of IL-10 and IL-10/TNF-alpha ratio gradually raised with the aggravation of the disease, and higher in PE group (P<0.05). (2) Circulating CD14+ monocyte HLA-DR expression, CD3+T cells, CD4+T cells, CD8+T cells, and NK cells gradually decreased, and lower in PE group (P<0.05). There was no significant difference in B cells, immunoglobulin and complement among the four groups. (3) The proportion of CD4+CD25+ Foxp3high Treg cells, mRNA level of Foxp, and serum concentrations of TGF-beta gradually decreased with the aggravation of the disease, while the proportion of Th17 cells, serum concentrations of IL-17A, mRNA level of ROR-gammat, and IL-6 gradually increased with the aggravation. CONCLUSION: Immune function changed with different illness phases. The mild cases presented systemic inflammatory response syndrome status, while critically ill cases presented compensatory anti-inflammatory response syndrome or mixed antagonist response status. Immunoregulatory treatment of patients with EV71 infection should emphasize different methods at different stage and individualization.

[Study of the clinical and laboratory features of hand-foot-mouth disease].

OBJECTIVE: To study the clinical and laboratory features of the mild and severe hand-foot-mouth diseases (HFMD) in Shenzhen in 2008. METHODS: 145 cases were observed in East-Lake Hospital and Shenzhen Children's Hospital. Of the 145 cases, 124 mild cases and 21 severe cases were involved.All the clinical data and laboratory findings were collected and summarized. After collection of the acute and convalescent consecutive stools and peripheral bloods from the patients with HFMDI, EV71 genes were amplified from these samples by RT-PCR. Enterovirus 71 were cultured and isolated using Vero cell line and R&D cell line. RESULTS: The WBC counts and blood glucose levels of the severe cases were significantly elevated, but the ages of the severe ones significantly decreased compared with those of the mild cases (P < 0.05). EV71 genes could be detected by RT-PCR with 35% positive rate in mild cases and 67% in severe cases. The EV71 gene detection rate of the severe cases was significantly increased in contrast to that of the mild ones. The EV71 were isolated and cultured from the stools of 9 patients, one specimens from the dead's stool. Two severe cases died of neurogenic pulmonary edema and brain-stem encephalitis. CONCLUSIONS: EV71 mainly contributes to HFMD and is responsible for death of some severe cases. High fever, less rash, elevated white blood cell counts and blood glucose concentrations as well as age less than 4 years old should be used for prediction of severe cases.