Objective:To summarize the clinical characteristics of children with interleukin-1 receptor associated kinase 4 (IRAK4) deficiency.Methods:The clinical data of a child with IRAK4 deficiency who was admitted to the Department of Neurology of Shenzhen Children′s Hospital for several times from June 2019 to August 2020 were retrospectively analyzed. Related literature up to January 2021 with the key words "IRAK4 gene variation", and "interleukin-1 receptor-associated kinase 4 deficiency" in PubMed, CNKI, Wanfang, and CQVIP databases were searched. The clinical characteristics of this disease were summarized and analyzed.Results:The boy was 6 years of age and had recurrent respiratory tract infections. He was improved after antibiotic treatment. His clinical manifestation included Streptococcus pneumoniae meningoencephalitis, multiple sclerosis, invasive discitis and inflammatory bone destruction. Family-based whole exome sequencing showed that the boy had a homozygous frameshift variation in the IRAK4 gene, NM_016123.3:C.540del (p.Phe180leufs*26), and both parents were heterozygous. A total of 23 cases were reported in ten English articles. Together with this case, there were 24 cases, including 13 males and 11 females. The age of onset was 8 days to 7 years. The main manifestations were recurrent invasive bacterial infection, including 11 cases with Streptococcus pneumoniae meningitis, 9 cases with Streptococcus pneumoniae and (or) Staphylococcus aureus septicemia, 1 case with Pseudomonas aeruginosa meningitis, 1 case of salmonella infection, and 1 case with Staphylococcus aureus skin abscess. Only 1 case had recurrent virus infection. There were 2 patients with autoimmune diseases, 1 with autoimmune encephalitis and the other one with juvenile idiopathic arthritis. Among the 24 cases, 10 died (9 in infancy). Most of the surviving children were diagnosed early and received antibiotics preventively and intravenous immunoglobulin (IVIG). Their susceptibility to infection decreased year by year, and could be close to normal children at the age of 14 years. Among the 24 cases, 21 cases had homozygous variation of IRAK4 gene and 3 cases had complex heterozygous variation. There were 15 kinds of variation, including 9 kinds of frameshift variation, 4 kinds of nonsense variation and 2 kinds of missense variation. One candidate variation hotspot was c.877 c>T (3 cases). Conclusions:IRAK4 deficiency mainly manifest as recurrent and invasive bacterial infection, with Streptococcus pneumoniae meningitis or septicemia being the most common. A few patients are complicated with autoimmune diseases. The mortality rate is high in infancy, early diagnosis and treatment can avoid severe illness or death.

Objective:To summarize the clinical phenotype of patients with developmental and epileptic encephalopathy 85 caused by SMC1A gene truncating variation.Methods:The clinical data of 4 patients with epileptic encephalopathy caused by SMC1A gene truncating variation from August 2016 to June 2020 were analyzed retrospectively. Related literatures up to October 2021 with the key words "SMC1A" "Developmental and epileptic encephalopathy 85" "SMC1A, epilepsy" and "SMC1A, truncating" in PubMed, CNKI, and Wanfang databases were searched. Relevant literature was summarized and reviewed.Results:These 4 patients were all female. The onset age of seizure were all in the infantile period. They were admitted to the hospital at 3, 2, 11 and 18 months respectively. Focal seizures occurred in all 4 patients, while 1 of them experienced infantile spasm. The characteristic of cluster was observed in all of them with an interval of 14 days to 5.0 months. The seizures were all refractory to different kinds of anti-seizure medications. All 4 patients had severe developmental retardation with microcephaly (head circumference<-2 s). The interictal electroencephalogram (EEG) was characterized by diffuse slow wave. The 4 SMC1A gene variants were p.Gly655fs, p.Glu811fs, p.Arg412fs and p.Ile143fs, all of which were de novo frameshift variation after parental validation. There were another 17 cases with SMC1A gene truncating variation reported in 6 English articles and 1 Chinese article. Among these 21 patients, who were all female, the onset of seizures occurred between 0.5 and 18.0 months of age. Seventeen cases (81%) had the characteristics of cluster attacks, and the intervals of attack cycles were different. Seizure types included generalized tonic-clonic seizure (12 cases (57%)), focal seizure (11 cases(52%)), myoclonic(4 cases(19%)), spasm (4 cases(19%)), atypical absence (3 cases(14%)), tonic seizure (2 cases (10%)), and atonia (1 case(5%)). In addition, 4 cases (19%) had status epilepsy. All patients had moderate to severe mental retardation. Microcephaly was found in all patients. Among 18 cases,EEG in 8 cases had diffuse slow wave background. Brain magnetic resonance imaging (MRI) was normal in 13 cases (62%). Other MRI changes included cerebellar atrophy (3 cases), thin corpus callosum (3 cases), and lateral ventricular enlargement (2 cases). Twenty patients did not respond well to antiepileptic drugs. Conclusions:The clinical phenotypes of patients with epilepsy encephalopathy 85 caused by SMC1A gene truncating variation are characterized by female, early-onset, clustering of seizures, development delay and microcephaly. Diffuse slow waves are shown in interictal EEG in partial. Response to treatment and prognosis are poor.

The main clinical phenotypes, imaging features and genetic test results of a child with Joubert syndrome treated in Shenzhen Children′s Hospital in July 2020 were analyzed retrospectively, and the literature on Joubert syndrome was summarized.The main manifestations of the protester during infancy were respiratory abnormalities and developmental retardation.The brain magnetic resonance imaging (MRI) showed a " molar sign" , which was consistent with the diagnosis of Joubert syndrome.Genetic testing suggested that the protestor carried complex heterozygous variations of KIAA0586 gene.Two variants were not reported previously, one of which was synonymous mutation.The child is the first case of Joubert syndrome caused by KIAA0586 gene in China.Joubert syndrome is a rare congenital brain development malformation characterized by high clinical heterogeneity and MRI molar signs.It may involve multiple systems.Early identification and intervention can improve outcomes.