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Objective@#To summarize the clinical manifestations and determine the molecular etiology for two collagen type Ⅵ-related myopathy pedigrees.@*Methods@#Two spontaneous collagen type Ⅵ-related myopathy patients were admitted to Department of Neurology, Children′s Hospital, Capital Institute of Pediatrics in October 2017. Clinical data of probands and their family members were collected and their genomic DNA was obtained for genetic testing. Next generation sequencing was performed and the variants were verified by the Sanger sequencing in the family members.@*Results@#Target region sequencing indicated that the proband of family 1 has carried a heterozygous variant of COL6A3 gene, c.6229G>C(p.Gly2077Arg), and it was de novo variant confirmed by Sanger-sequencing in the family.The patient 1, a 2-year-three-month old boy, was admitted due to motor retardation at birth. He was defined as early severe Ullrich congenital muscular dystrophy. He never achieved independent ambulation, he had onset of symptoms was found at birth, including diffuse muscle weakness, striking distal joint hyperlaxity, proximal contractures, calcaneal protrusion, kyphosis, and hip dislocation. Serum CK level was elevated slightly and EMG showed neurogenic changes. The patient 2, a 7-year-old girl with a limp for 4 years, carried one de novo variant of COL6A3 gene,c.5169_5177del (p.Glu1724_Leu1726del). This variant results in the deletion of amino acids (1724 to 1726) in α3 chain of collagen Ⅵ, which may disturb the function of this protein.She was diagnosed as Bethlem myopathy with a mild phenotype. She had delayed motor milestones and presented with walking on tiptoe, hypotonia, and ithylordosis. The contracture of proximal joints was not very obvious. Serum CK level was normal and EMG showed myogenic changes.Muscle biopsy revealed muscular dystrophy and muscle magnetic resonance imaging of patient 2 showed vastus lateral is a "sandwich" sign. Immunofluorescence staining for COL6A3 chain in the cultured skin fibroblasts from patients 2 showed decreased deposition compared with control.@*Conclusions@#These two patients were diagnosed as spontaneous collagen type Ⅵ-related myopathy and carried different variants of COL6A3 gene. Different in pathogenetic variants could cause different genetic features and different phenotypes. Collagen type Ⅵ- related myopathy patients have various clinical manifestations. Typical phenotypes include muscular dystrophies, proximal contractures, and distal hyperlaxity. Muscle MRI shows diffuse fatty infiltration of gluteus maximus and thigh muscle. The histological staining showed the low level expression of COL6A3 chain. The seventy of phenotype was related to the genotype.
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Objective To analyze the clinical characteristics and genetic variation of megalencephalic leu-koencephalopathy with subcortical cysts(MCL),then to explore the genetic characteristics so as to help families by pro-viding genetic counseling. Methods The clinical data of the children and their family members were collected,and the peripheral blood DNA of the children and family members were extracted. Then,the MLC1 gene mutation in the children was detected by using the target sequence capture high-throughput sequencing technology and Sanger sequencing tech-nology. Results (1)MCL often presented abnormal head circumference in infants as the first symptom. The main clini-cal manifestations were hypoevolutism in motor development,retrogression of early school age,then the movement disor-der progressed and finally paralyzed;epilepsy was common in early childhood;head magnetic resonance imaging showed white matter in bilateral cerebral hemisphere diffusing abnormal signal with temporal lobe cystic change in the early stage,and then showed brain atrophy. (2)The gene results showed that the 2 girls with MLC had both c. 368C >T (p. Thr123Ile)and c. 353C > T (p. Thr118Met)complex heterozygous variation,which existed in the MLC1 gene. The girls′ father and a sister carried c. 368C > T (p. Thr123Ile),while the mother carried c. 353C > T (p. Thr118Met) heterozygous variation,all of whom were normal phenotypes. Conclusions MCL is one cause of hypoevolutism in motor development in children and abnormal head circumference of infants is usually the first symptom. The MLC1 gene c. 368C> T(p. Thr123Ile)is a pathogenic mutation for MLC,and may be another new pa-thogenic mutation.
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Objective To analyze the clinical characteristics of narcolepsy in children with obesity,and to e-valuate the impact of obesity on narcoleptic children clinically. Methods Forty cases first diagnosed as narcolepsy were recruited in the study who to see doctors at the Department of Neurology,Children's Hospital of Capital Institute of Pediatrics,from July 2012 to January 2015. According to diagnostic criteria for obesity by the body mass index(BMI) growth curve for the Chinese children and adolescents,they were divided into the obese group and the nonobese group. The general clinical data of 2 groups were analyzed,and the related metabolic indexes and the whole night polysomnog-raphy(PSG)of 2 groups were studied. Results In this group,male versus female 3: 1,obesity was found in 21 cases (52. 5% )and nonobesity was found in 19 cases(47. 5% )from the samples. The mean BMI of all patients was (21. 55 ± 3. 11)kg/ m2 . The average BMI of the obese group was(23. 09 ± 2. 46)kg/ m2 ,and BMI of the non - obese group was(19. 85 ± 2. 89)kg/ m2 . Obese children were younger at the onset of disease and by the time of diagnosis age [(7. 94 ± 2. 22)years old,(8. 76 ± 2. 36)years old]than nonobese children[(10. 75 ± 3. 10)years old,(12. 51 ± 2. 88)years old]. The fasting blood glucose and blood lipid in all patients were normal,and there was no significant difference between 2 groups. The total sleep time,sleep efficiency and the ratio of rapid eye movement(REM)phase of the obese group[(397. 45 ± 53. 76)min,(68. 70 ± 8. 90)% ,(18. 37 ± 4. 39)% ]were significantly lower than those of the non - obese group[(449. 95 ± 86. 49)min,(76. 58 ± 13. 60)% ,(22. 19 ± 6. 34)% ]. According to the sleep structure,the percentage of stageⅠnon rapid eye movement(NREM)sleep in the obese group[(20. 90 ± 6. 38)% ] was more than that in non - obese group[(16. 26 ± 4. 22)% ]. There was no difference between the percentage of stageⅡNREM sleep in the obese group[(42. 59 ± 5. 52)% ]and the non - obese group[(38. 54 ± 8. 74)% ]. Stage Ⅲ + Ⅳ(slow wave sleep)NREM sleep ratio in the obese group[(18. 14 ± 6. 97)% ]was significantly lower than that in the non - obese group[(22. 60 ± 5. 69)% ]. Conclusions Obesity is one of the most common comorbids in narcolepsy, which affects more than 50% of narcoleptic children,mostly younger at disease onset. The narcolepsy children with obe-sity has total sleep time decreased,sleep efficiency reduced and sleep structure disorder is more obvious. To improve the realization of obesity in narcolepsy children and early treatment is the key to the success of the therapy.
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Objective To explore the clinical characteristics,diagnosis,treatment and outcomes of anti-N-methyl-D-aspartate receptor(anti-NMDAR) encephalitis in children.Methods Six children diagnosed as anti-NMDAR encephalitis were recruited at the Department of Neurology,Capital Institute of Pediatrics,from December 2011 to April 2013.The data of clinical characteristics and laboratory examinations were retrospectively analyzed.All the children had long-term follow-ups and the prognosis was assessed.Results (1) Age and course of the disease at the time of the admission:the mean age of the 6 patients (2 female) was 3 years and 5 months,ranging from 2 years and 2 months to 6 years and 8 months.The course of the disease at the time of the admission ranged from 15 to 80 days,with a mean time of 39 days.(2)Clinical characteristics:5 cases had afebrile convulsion and 1 case had speech impairment at the onset of disease.Convulsion occurred in all the 6 cases,4 cases of whom had persistent convulsion,and 5 cases had impaired consciousness.All the 6 cases exhibited aphasia,and complicated with mental or emotional abnormalities,irritability or shouting.Five cases developed into sleep disorders such as sleep deprivation.Five cases had limb and facial involuntary movement,in which 2 cases had stereotyped action.Prominent autonomic nervous dysfunction including hidrosis was found in 1 case.(3) Laboratory examination:cerebrospinal fluid test was normal in 6 cases,and 1 case had slightly increased white blood cell level.Specific anti-NMDAR antibody was positive in serum and/or cerebrospinal fluid in the 6 cases.Electroencephalograph of the 6 cases showed slow wave background during lucid interval,and 5 cases had interictal epileptiform discharges.The skull MRI showed cerebral atrophy 4 cases,and 2 cases of them were complicated with encephalomalacia.No tumor was found in the patients.(4) Treatment and follow-ups:6 cases received gamma globulin or methylprednisolone or other immunotherapy.Three cases received combined therapy with Rituximab,1 case received plasmapheresis,and 1 case received Cyclophosphamide.Follow-ups lasted for 2 to 31 months.Three patients had clinical recovery,and varying degrees of neurological complications were found in 3 cases.Conclusions (1) Anti-NMDAR encephalitis is common in children.(2) The specificity of its clinical symptoms is not strong.The incidence of convulsion is high,and different degrees of consciousness disorders may occur in some of the severe patients.Degeneration of language function and emotional changes can be observed.Most pediatric patients have abnormal movement,and the symptoms of automatic nervous system are not prominent.(3) The disease can be confirmed by the specific anti-NMDAR antibody in the spinal fluid or plasma.(4) The time of clinical recovery is long,and an early immunotherapy is associated with a better prognosis.