[Risk factors for pulmonary atelectasis in adults with tracheobronchial tuberculosis].

Objective: To investigate the risk factors for pulmonary atelectasis in adults with tracheobronchial tuberculosis(TBTB). Methods: Clinical data of adult patients (≥18 years old) with TBTB from February 2018 to December 2021 in Public Health Clinical Center of Chengdu were retrospectively analyzed. A total of 258 patients were included, with a male to female ratio of 1∶1.43. The median age was 31(24, 48) years. Clinical data including clinical characteristics, previous misdiagnoses/missed diagnoses before admission, pulmonary atelectasis, the time from symptom onset to atelectasis and bronchoscopy, bronchoscopy and interventional treatment were collected according to the inclusion and exclusion criteria. Patients were divided into two groups according to whether they had pulmonary atelectasis. Differences between the two groups were compared. Binary logistic regression was used to analyze the risk factors for pulmonary atelectasis. Results: The prevalence of pulmonary atelectasis was 14.7%, which was most common in the left upper lobe (26.3%). The median time from symptom onset to atelectasis was 130.50(29.75,358.50)d, and the median time from atelectasis to bronchoscopy was 5(3,7)d. The median age, the proportion of misdiagnosis of TBTB before admission, and the time from symptom onset to bronchoscopy in the atelectasis group were higher than those without atelectasis, and the proportion of receiving bronchoscopy examination and interventional therapy previously, and the proportion of pulmonary cavities were lower than those without atelectasis (all P<0.05). The proportions of cicatrices stricture type and lumen occlusion type in the atelectasis group were higher than those without atelectasis, while the proportions of inflammatory infiltration type and ulceration necrosis type were lower than those without atelectasis (all P<0.05). Older age (OR=1.036, 95%CI: 1.012-1.061), previous misdiagnosis(OR=2.759, 95%CI: 1.100-6.922), longer time from symptom onset to bronchoscopy examination (OR=1.002, 95%CI: 1.000-1.005) and cicatrices stricture type (OR=2.989, 95%CI: 1.279-6.985) were independent risk factors for pulmonary atelectasis in adults with TBTB (all P<0.05). Of the patients with atelectasis who underwent bronchoscopy interventional therapy, 86.7% had lung reexpansion or partial reexpansion. Conclusions: The prevalence of pulmonary atelectasis is 14.7% in adult patients with TBTB. The most common site of atelectasis is left upper lobe. The TBTB type of lumen occlusion is complicated by pulmonary atelectasis in 100% of cases. Being older, misdiagnosed as other diseases, longer time from onset of symptoms to bronchoscopy examination, and being the cicatrices stricture type are factors for developing pulmonary atelectasis. Early diagnosis and treatment are needed to reduce the incidence of pulmonary atelectasis and increase the rate of pulmonary reexpansion.

[Clinical characteristics of 25 patients with type â interferonopathies].

Objective: To summarize the clinical characteristics of type I interferonopathies and provide clues for early identification and diagnosis. Methods: Clinical data of 20 patients admitted to Department of Pediatrics, Peking Union Medical College Hospital and 5 patients admitted to Department of Rheumatology and Immunology, Shenzhen Children's Hospital from January 2016 to September 2021 were retrospectively analyzed. The data included gene results, clinical manifestations and auxiliary examination results. Results: Of the 25 cases, 12 were males and 13 were females. Age of onset ranged from 1 day to 11 years. And 84% of them had the onset before the age of 3 years. The cases consisted of 14 cases of Aicardi-Goutières syndrome (AGS), 6 cases of adenosine deaminase 2 deficiency (DADA2), 3 cases of stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI), and 2 cases of Spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Eighteen patients (72%) experienced neurologic disorder, among whom 16 (64%) showed intracranial calcification, 11 (44%) had dystonia, 10 (40%) had leukodystrophy, 6 (24%) had epilepsy, 5 (20%) had brain atrophy and 5 (20%) had early-onset cerebrovascular events. Skin involvement occurred in 15 cases (60%), among whom 8 cases (32%) had chilblain-like rash, 4 cases (16%) had livedo reticularis, 3 cases (12%) had erythema, 2 cases (8%) had erythema nodosum and 2 cases (8%) had Raynaud's phenomenon. In addition, 12 cases (48%) had positive autoimmune antibodies, 10 cases (40%) manifested as developmental retardation, 8 cases (32%) experienced lung interstitial lesions, and 7 cases (28%) demonstrated thyroid dysfunction. And 1 died (4%) at 11 years of age. Conclusions: Type Ⅰinterferonopathies can involve multiple organs, and share the characteristics of systemic inflammatory and autoimmune diseases. The early-onset neurological symptoms (early-onset cerebrovascular events, intracranial calcification, leukodystrophy and cerebral atrophy), rashes (chilblain-like rash, livedo reticularis and erythema), positive autoimmune antibodies, developmental delay, interstitial lung disease and thyroid dysfunction may indicate type Ⅰ interferonopathies.

[QARS1 gene related glutaminyl-tRNA synthetase deficiency syndrome: report of three cases and a review of literature].

Objective: To investigate the clinical characteristics, treatment and prognosis of QARS1 gene related glutaminyl-tRNA synthetase deficiency. Methods: To summarize and analyze the clinical manifestations, imaging, laboratory examination, genetic variant characteristics and treatment of three patients from the Fujian Medical University Affiliated Union Hospital, the 900th Hospital of People's Liberation Army, the First Medical Center of People's Liberation Army General Hsopital carrying compound heterozygous variations in QARS1 gene with a long-term follow-up in China. A literature search was conducted using Wanfang, Weipu, China National Knowledge Infrastructure (CNKI) and Pubmed databases with the keywords "QARS", "QARS1" and "glutaminyl-tRNA Synthetase"(up to December 2019). Results: Case 1, a female 53 days of age, was admitted to the Fujian Medical University Affiliated Union Hospital for treatment because of the complaint of repetitive seizures for one month after birth and fever for one day. The seizure occurred within the first 2 hours of life with multiple forms and often had a status as persisted from hours to days. The seizures were resistant to many anti-epilepsy drugs (AED) and ketogenic diet but later controlled by clonazepam. However, she died at the age of seven years. Case 2 (younger brother of case 1), a one-hour-old boy, was hospitalized because of seizures after birth for 1 hour. Intrauterine growth retardation was discovered during late-pregnancy. The boy presented seizures and microcephaly immediately after birth, and his epilepsy was pharmacoresisitant. Case 3, an 8-month-old girl, was admitted due to recurrent convulsions for nearly two months. The girl had mild developmental retardation and hypotonia after birth. The infantile spasm was observed at her age of 6 months and disappeared under treatment with Vitamin B6, vigabatrin combined with adreno-cortico-tropic-hormone and magnesium sulfate. However, the seizure pattern turned to tonic seizures later. She was seizures free now with clobazam and zonisamide treatment. All of them manifested as a syndrome composed of severe global developmental retardation, progressive microcephaly, hypotonia from the very beginning, mild hypoproteinemia and diffuse brain atrophy. Genetic studies revealed compound heterozygous variations of QARS1 gene which were not reported previously. A review of the literature reported a total of 22 patients from 18 unrelated families all over the world. Except for 5 cases without epilepsy,all the patients shared very similar clinical manifestations as classic pentalogy. The recommended effective treatment for epilepsy has not been reported yet. Conclusions: Glutaminyl-tRNA synthetase deficiency caused by QARS1 gene variations manifested as a clinical syndrome's pentalogy, characterized by microcephaly, cerebral atrophy, intractable early-onset epileptic encephalopathy, global developmental retardation and severe muscle hypotonia.

[Rapamycin in the treatment of renal diseases associated with tuberous sclerosis complex].

Objective: To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods: A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People's Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m(2)·d), which was gradually adjusted to reach a blood concentration of 5-10 µg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results: Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions: Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.

[Effects of ubiquitin-specific proteases 2-69 on proliferation of breast cancer cells].

Objective: To investigate the expression and significance of ubiquitin-specific proteases 2-69(USP2-69) in invasive ductal carcinoma of breast. Methods: Twenty-four cases of human breast tissue with invasive ductal carcinoma diagnosed at Huanshan Hospital, Fudan University from 2013 to 2015 were collected, and the expression of USP2-69 mRNA and protein was detected by molecular hybridization, Western blot and immunohistochemistry. USP2-69 was over-expressed in cultured human breast cancer cell line MCF-7 by USP2-69 plasmid transfection. The cellular proliferative activity was investigated in vitro. Results: The USP2-69 mRNA and protein were highly expressed in breast invasive ductal carcinoma, compared to adjacent normal tissues (P<0.01). Ki-67 protein expression was also increased in cases with high USP2-69 protein level. Western blot showed significantly higher USP2-69 protein level in cancer tissue compared to the adjacent normal tissue. In the cultured tumor cells, there was increased S phase fraction, cellular proliferation rate, flat positive clones, cyclin D1 expression and decreased p27 expression in USP2-69-transfected MCF-7 cells. Conclusions: USP2-69 is over-expressed in breast invasive ductal carcinoma, and is closely related to proliferation promoting effects. The data provide an important experimental basis for further study on the molecular mechanism of breast cancer cell proliferation.

[Investigation on immunization program coverage rate and its safety in children with tuberous sclerosis].

Objective: To investigate the status of immunization of National Immunization Program (NIP) and its adverse reaction rate in children with tuberous sclerosis. Method: Questionnaire survey was adopted to identify the vaccination coverage and its adverse events; 72 cases of children with tuberous sclerosis and 78 normal controls (healthy children completing age-appropriate NIP) admitted to Chinese People's Liberation Army General Hospital from December 2014 to November 2015 were involved into this study. Result: The age-appropriate NIP coverage rate of tuberous sclerosis was 36%(26/72). The coverage rate of bacillus calmette-guerin (BCG), hepatitis B vaccine 1st to 3rd doses (HepB1-3), oral poliovaccine 1st dose (OPV1), diphtheria, pertussis and tetanus 1st dose (DPT1), DPT1-3, meningococcal polysaccharide vaccine group A (MPVA), measles amd rubella vaccine/measles vaccine 1st dose (MRV/MCV1), and Japanese encephalitis vaccine 1st dose (JEV1) were 100%(72 cases), 75%(51 cases), 97%(66 cases), 91%(62 cases), 82%(56 cases), 66%(45 cases), 69%(42 cases), and 61%(37 cases) respectively. The reasons why the children did not complete the vaccination plan were that parents were concerned about vaccination-induced seizures or seizures had not been controlled. Among 72 children with TSC, the rate of adverse events or suspected adverse events after vaccination was 17% (12 cases), which was higher than the normal control children (2 cases, 3%) (χ2=8.799, P<0.05). The main adverse events were seizure events, which accounted for 92%(11 cases). Conclusion: The age-appropriate NIP coverage rate among children with tuberous sclerosis is low. The high incidence of adverse events may be associated with a fact that there are some nervous system abnormalities in cases with tuberous sclerosis. TSC children vaccination is relatively safe, with no serious adverse events.

Phenotypic and genotypic characterization of Chinese children diagnosed with tuberous sclerosis complex.

We investigated the clinical phenotypes and genetic mutations in Chinese children diagnosed with tuberous sclerosis complex (TSC). Sequencing of TSC1 and TSC2 genes was performed in 117 children with TSC and their parents. Association of TSC gene mutations with clinical manifestations was investigated. All gene mutations were heterozygous including in 16 patients (13.7%) with mutations in TSC1 gene and 101 patients (86.3%) with mutations in TSC2 gene. Among the 16 patients with TSC1 gene mutations, 15 different types of mutations were found, which included 5 novel mutations; all patients had skin manifestations and epilepsy. Among the 101 patients with TSC2 mutations, 85 different types of mutations were found, which included 25 novel mutations; 97 patients (96.0%) had skin manifestations; 97 (96.0%) had epilepsy; 74 (73.3%) had intellectual disability and 25 patients (24.8%) were autistic. The clinical phenotype of the 14 children with familial TSC was more severe than that of their parents.

[Rapamycin in the treatment of cardiac rhabdomyoma associated with tuberous sclerosis complex].

OBJECTIVE: To assess the efficacy and safety of mammalian target of rapamycin (mTOR) inhibitor rapamycin in treatment of children with cardiac rhabdomyoma, associated with tuberous sclerosis complex (TSC). METHOD: The clinical data of children with cardiac rhabdomyomas, who had received a diagnosis of TSC previously, were collected between September 2011 and November 2015 from Pediatric Department of the People's Liberation Army General Hospital.Patients in line with the inclusion criteria received long-term treatment with sirolimus.The starting doses of sirolimus was 1 mg/ (m(2)·d), and the plasma concentration was maintained at 5-10 µg/L.The size and number of cardiac rhabdomyomas were analyzed after treatment with rapamycin, and the efficacy and safety were assessed. The Wilcoxon test was used to analyze data. RESULT: All the 51 children met the inclusion and exclusion criteria, including 30 males and 21 females.The median age for rapamycin treatment was 15.0 months (7.0-35.0 months). Tumors disappeared in 26 (51%) children, decreased by more than 50%(including 50%) in 15 (29%) children, decreased by less than 50% in 5 (12%) children, and had no change or progressed in 4 (8%) children.The number of tumors decreased by 77(72%). The median maximum diameter of tumor was 8.7 (5.9-11.3) mm before treatment, 0.0 (0.0-4.0) mm after treatment, and the median decrease of tumor size were 6.7 (3.9-10.0) mm (Z=-8.817, P<0.01). The median disappearance time was 3.26 (2.92-5.37) months.Among different age groups, after treatment by rapamycin, the rate of tumor's disappearance was 50% (12/24) in 0-1 years group.Tumors disappeared in 10 of 16 patients in >1-3 years group and in 4 of 11 patients in >3 years group.The rate of tumor's disappearance was the highest after 3 months of treatment as compared with 6 and 12 months of treatment.Ten children had adverse event that was related to rapamycin.Canker sore was reported in one child and dyslipidemia was reported in 9 children. CONCLUSION: Rapamycin is efficacious and well tolerate in treatment of cardiac rhabdomyomas associate with TSC, and lead to a reduction in tumor size and number, in addition, significantly shorten the duration of cardiac rhabdomyoma.

A study of 133 Chinese children with mitochondrial respiratory chain complex I deficiency.

To investigate the clinical, enzymological and mitochondrial gene profiles of complex I deficiency in Chinese, clinical and laboratory data of the patients (79 boys, 54 girls) were retrospectively assessed. Activities of mitochondrial respiratory chain complexes in peripheral leucocytes were spectrophotometrically measured. The entire mitochondrial DNA (mtDNA) sequence was analyzed in 62 patients. Restriction fragment length polymorphism and gene sequencing analyses were performed in 15 families. Ninety-one patients had isolated complex I deficiency; 42 had combined deficiencies of complex I and other complexes. The main clinical presentations were neuromuscular disorders (107 patients) and non-neurological dysfunction (hepatopathy, renal damage and cardiomyopathy; 26 patients). In 32 of 62 patients who underwent mtDNA sequencing, 24 mutations were identified in 15 mitochondrial genes. The 12338T>C, 4833A>G and 14502T>C mutations were found in 12.9%, 11.3% and 4.8% patients, respectively. Seven patients had multiple mutations. Three novel mutations were identified. Chinese patients with complex I deficiency presented heterogeneous phenotypes and genotypes. Twenty-four mutations were identified in 15 mitochondrial genes in 51.6% patients. mtDNA mutations were more common in isolated complex I deficiency than in combined complex deficiencies. The 12338T>C, 4833A>G and 14502T>C mutations were common.

Association of SCN1A gene polymorphisms with infantile spasms and adrenocorticotropic hormone responsiveness.

OBJECTIVES: Infantile spasms (IS) are severe epileptic encephalopathy during infancy. The SCN1A encodes the α1 subunit of the neuronal voltage-gated sodium channels, and mutations in SCN1A have been frequently detected in idiopathic epilepsy and encephalopathy, which had similar symptoms as IS. Therefore, we investigated the association of SCN1A polymorphism with the IS and the responsiveness to adrenocorticotropic hormone (ACTH) treatment in the present study. PATIENTS AND METHODS: We totally collected 113 IS patients and and 122 age-matched healthy controls. All of the subjects were Han Chinese descent, and the 113 cases were further divided into subgroups of cryptogenic and symptomatic patients. Nine tag SNPs within the SCN1A gene were selected and genotyped by the direct sequencing of PCR-amplified products. The ACTH was then applied to all of the cases. RESULTS: Two SNPs in high linkage disequilibrium, rs13397210 and rs760543, were significantly associated with IS under genotype model (p = 0.015). In addition, we also found that a 4-SNP haplotype (CAGC) which contains the aforementioned 2 SNPs, was associated with increased responsiveness to ACTH therapy in IS (p = 0.018, OR = 4.8) under recessive model. Of the 2 subgroups of cases, more cryptogenic patients responded to the ACTH treatment than the symptomatic patients. CONCLUSIONS: The results suggested that genetic variants of the SCN1A gene were associated with IS and ACTH responsiveness.

Molecular and clinical characterization of Angelman syndrome in Chinese patients.

Angelman syndrome (AS) is a neurobehavioral disorder caused by lack of function of the maternal copy of the ubiquitin-protein ligase E3A (UBE3A) gene. In our study, 49 unrelated patients with classic AS phenotypes were confirmed by methylation-specific PCR (MS-PCR) analysis, short tandem repeat linkage analysis, and mutation screening of the UBE3A gene. Among the Chinese AS patients, 83.7% (41/49) had deletions on maternal chromosome 15q11.2-13. Paternal uniparental disomy, imprinting defects, and UBE3A gene mutations each accounted for 4.1% (2/49). Two AS patients were confirmed by MS-PCR analysis, but the pathogenic mechanism was unknown because their parents' samples were unavailable. Of the two described UBE3A gene mutations, that is, p.Pro400His (c.1199C>A) and p.Asp563Gly (c.1688A>G), the latter has not been reported previously. Mutation transmission analysis showed that the p.Pro400His and p.Asp563Gly mutations originated from asymptomatic mothers. The patients with the maternal deletion showed AS clinical manifestations that were consistent with other studies. However, the incidence of microcephaly (36.7%, 11/30) was lower than that in the Caucasian population (approximately 80%), but similar to that of the Japanese population (34.5%). Our study demonstrated that the occurrence of microcephaly in AS may vary among different populations.

Comparison of the GMFM-66 and the PEDI Functional Skills Mobility domain in a group of Chinese children with cerebral palsy.

BACKGROUND: Previous research has suggested there is a high level of comparability between the Gross Motor Function Measure-66 (GMFM-66) and the Pediatric Evaluation of Disability Inventory (PEDI) Functional Skills Mobility domain. However, there are only a few studies that have examined the correlations between these instruments. The purpose of this study was to determine the correlation between the GMFM-66 and the PEDI Functional Skills Mobility domain scaled scores in a group of Chinese children with spastic cerebral palsy, at the ages of 12-70 months, in order to explore the feasibility of using them interchangeably. METHODS: Secondary data analysis was conducted of data collected during a prospective international collaborative study that used the GMFM-66 and the PEDI to examine the impact of treatment. This study examined the Pearson correlations between the GMFM-66 and the PEDI Functional Skills Mobility domain at six time points over the course of 28 consecutive weeks for 115 Chinese children who participated at baseline. RESULTS: Pearson correlations between the GMFM-66 and the PEDI Functional Skills Mobility domain ranged from 0.83 to 0.90 for the six time points of data collection, with statistically significant P-values <0.0001 for each correlation. CONCLUSIONS: These results support previous research that the GMFM-66 and the PEDI Functional Skills Mobility domain are complementary assessments that may be used interchangeably when it is not possible to administer both.

The association of CTLA-4 and CD28 gene polymorphisms with idiopathic ischemic stroke in the paediatric population.

Autoimmune vasculitis is believed to be a critical factor in the development of idiopathic childhood ischemic stroke. The association of polymorphisms in CTLA-4 and CD28 with some immune vasculitides, such as systemic lupus erythematosus (SLE) and Behçet's disease has been reported. The aim of the present study is to investigate the association of the genetic variants in the CTLA-4 and CD28 genes of children who suffered idiopathic ischemic stroke using a case-control design. Two single nucleotide polymorphisms (SNPs) in the CTLA-4 gene and an SNP in the CD28 gene were genotyped in 51 patients who suffered idiopathic ischemic stroke, and in 74 healthy controls from mainland China. An SNP, CTLA-4+49A/G located in exon 1 of the CTLA-4 gene, showed nominal association with the disease (P = 0.012, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.17-3.73) using allele-based analysis. Homozygous carriers of the G allele of this SNP were more common in the patients than in the controls (P = 0.008). The CD28IVS3 +17TT genotype was found to be more common in the patients than in the controls (P = 0.039, OR = 2.96, 95% CI = 1.02-8.58). No correlations of at-risk genotype (G/G) of CTLA-4+49A/G and genotype (T/T) of CD28+17T/C with the main clinical features of idiopathic childhood ischemic stroke were observed. The results suggest that polymorphisms in the CTLA-4 and CD28 genes may contribute to the increased risk of idiopathic ischemic stroke.

Analysis of single nucleotide polymorphisms in the melanocortin-4 receptor promoter in infantile spasms.

OBJECTIVES: Infantile spasms is a severe epileptic encephalopathy of infancy. ACTH that ameliorates infantile spasms might act through activating the central melanocortin-4 receptor (MC4R) to suppress excessive production of corticotrophin-releasing hormone (CRH). This study aimed to elucidate an association between the genetic variants of the MC4R gene and infantile spasms. METHODS: The study population comprised 96 patients with infantile spasms and 118 controls. All subjects were screened for variations in the promoter and coding region of the MC4R gene using a direct sequencing method. ATCH responses in patients carrying different genotypes were also assessed. RESULTS: The distributions of genotypes and alleles of rs11872992 in the MC4R promoter were significantly different between cases and controls. The frequencies of heterozygous carriers (TC genotype) were significantly lower in cases (10%) than in controls (27%) (p=0.003). The distributions of rs11872992 TC and CC genotypes were significantly different between ACTH responders and non-responders (OR, 0.14; 95% C.I, 0.03-0.69; p=0.007). The T-allele carriers (83.3%) had a higher responsiveness to ACTH than non-carriers (41.7%). CONCLUSIONS: The present study shows that genetic variants in the MC4R promoter are associated with the development of infantile spasms. The rs11872992 polymorphism influences ACTH treatment responses in patients with infantile spasms.