Objective: To investigate the clinical manifestations and genetic features of 2 children with Smith-Kingsmore syndrome caused by MTOR gene variation and review the literature. Methods: The clinical data of 2 children carrying MTOR gene variant, diagnosed at Xi'an Children's Hospital from April 2018 to April 2021, were retrospectively summarized."MTOR"and"Smith-Kingsmore syndrome"were used as key words to search at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed and OMIM up to August 2021. The characteristics of MTOR gene variation and the clinical phenotype of children with Smith-Kingsmore syndrome were summarized. Results: Two children were both females, aged 1.5 years and 2 years respectively, the onset age were both in infancy. They both had developmental delay, megalencephaly and abnormal face. Both whole exome sequencing revealed a de novo heterozygous missense variant in MTOR gene. One case carried c.5395G>A (p.Glu1799Lys) and the other case carried c.7234G>C (p.Asp2412His). There was no literature of MTOR gene variation in Chinese. So far, a total of 45 cases were reported worldwide with detailed clinical information. Eleven variations in MTOR gene were involved, which were all heterozygous missense mutations. Among them, p.Glu1799Lys was the most common sites (28 cases,62%). Another case carried c.7234G>C (p.Asp2412His) was not reported before. Summarizing the 47 cases (including these 2 cases), 46 cases had developmental delay or intellectual disability, 9 cases had developmental regression,42 cases had megalencephaly, 30 cases had facial malformation,16 cases had hypotonia, 17 cases had autism spectrum disorders, 3 cases had hyperactivity, 3 cases had obsessive compulsive disorder, 13 cases had eye diseases, 11 cases had cutaneous vascular malformation, and 9 cases had hypoglycemia. Conclusions: The main clinical features of Smith-Kingsmore syndrome include megalencephaly, developmental delay or intellectual disability, and facial malformation, which can be combined with epilepsy, autism spectrum disorder, hypotonia, hypoglycemia and so on. The variation of MTOR gene is the cause of Smith-Kingsmore syndrome.
Autism Spectrum Disorder ; Female ; Humans ; Hypoglycemia ; Intellectual Disability/genetics* ; Megalencephaly/genetics* ; Muscle Hypotonia ; Mutation ; Retrospective Studies ; TOR Serine-Threonine Kinases/genetics*

BACKGROUND AND PURPOSE: A thick corpus callosum (TCC) can be associated with a very grave outcome in fetuses, but its clinical presentation in older children seems to be markedly different. METHODS: The corpus callosum (CC) was defined as thick based on observations and impressions. We reviewed cases of children who were diagnosed as TCC based on brain magnetic resonance imaging (MRI) studies. The pertinent clinical data of these children were collected, and their CCs were measured. RESULTS: Out of 2,552 brain MRI images, those of 37 children were initially considered as showing a TCC. Those initial imaging were reviewed by an experienced neuroradiologist, who confirmed the diagnosis in 34 children (1.3%): 13 had neurofibromatosis-1 (NF-1), 9 had epilepsy, 3 had macrocephaly capillary malformation (MCM) syndrome, 3 had autistic spectrum disorder, 1 had a Chiari-1 malformation, and 1 had increased head circumference. No specific neurologic disorder could be defined in seven children. The measured thickness of the CC in these children was comparable to those published in the literature for adults. CONCLUSIONS: A TCC is a rare brain malformation that can be found in neuropathologies with apparently diverse pathognomonic mechanisms, such as NF-1 and MCM. It is not necessarily associated with life-threatening conditions, instead being a relatively benign finding, different in nature from that reported in fetuses.
Adult ; Brain ; Capillaries ; Child* ; Corpus Callosum* ; Diagnosis ; Epilepsy ; Fetus ; Genetics ; Head ; Humans ; Magnetic Resonance Imaging ; Megalencephaly ; Nervous System Diseases ; Neurofibromatoses ; Neuropathology

OBJECTIVETo reprogram the 1q21.1 microdeletion pluripotent stem cells in order to establish an ideal model for further studying its pathogenesis.

METHODSHuman amniotic fluid-derived cells induced pluripotent stem cells (hAF-iPSCs) were induced from amniotic fluid cells harboring the 1q21.1 microdeletion by retroviral vectors encoding Oct4, Sox2, c-Myc and Klf4. Characteristics of the 1q21.1 microdeletion hAF-iPSCs were determined, which included in vitro pluripotency, karyotype, microarray analysis, the capacity of differentiation in vivo and in vitro, etc.

RESULTShAF-iPSCs derived from amniotic fluid cells harboring the 1q21.1 microdeletion have maintained self renewal, with expression of pluripotency marker genes detectable at mRNA level. Stem cell surface antigens were tested by immunocytochemistry. The 1q21.1 microdeletion hAF-iPSCs showed a normal karyotype after long-term culturing in vitro, and harbored the same microdeletion as confirmed by microarray analysis. The cells have maintained their differentiation capacity both in vivo and in vitro.

CONCLUSIONThe hAF-iPSCs harboring the 1q21.1 microdeletion have all the characteristics of normal pluripotent stem cells, and can be used for directed differentiation into specific cells, which may provide an ideal model for studying the pathogenesis of 1q21.1 microdeletion in vitro.

Abnormalities, Multiple ; embryology ; genetics ; physiopathology ; Adult ; Amniotic Fluid ; cytology ; Animals ; Cell Differentiation ; Chromosome Deletion ; Chromosomes, Human ; genetics ; Chromosomes, Human, Pair 1 ; genetics ; Female ; Fetal Diseases ; genetics ; physiopathology ; Gene Deletion ; Humans ; Induced Pluripotent Stem Cells ; cytology ; Male ; Megalencephaly ; embryology ; genetics ; physiopathology ; Mice ; Mice, SCID ; Models, Biological ; Pregnancy ; Young Adult