Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

Clinical and genetic analysis of three children with KBG syndrome due to novel variants of ANKRD11 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of three children with KBG syndrome.@*METHODS@#Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out.@*RESULTS@#All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib- pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC (p.D2286Efs*51) variant of the ANKRD11 gene, which was inherited from his mother who had a mild clinical phenotype.@*CONCLUSION@#The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.

A case of Rubinstein-Taybi syndrome caused by a variant of EP300 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a child with Rubinstein-Taybi syndrome (RSTS).@*METHODS@#A child who was admitted to the Children's Hospital of Soochow University on October 3, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing of his family members and bioinformatic analysis.@*RESULTS@#The patient, a 9-year-and-４-month-old boy, had manifested unique facies, microcephaly, broad toes, growth retardation, and intellectual impairment. WES revealed that he has harbored a heterozygous c.3604G>T (p.E1202*) variant in exon 20 of the EP300 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant was not found in the Shenzhou Genome data Cloud, ExAC, 1000 Genomes and gnomAD databases．Analysis with SIFT, PolyPhen-2 and CADD online software has predicted the variant to be harmful. Based on the guidelines formulated by the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1＋PS2＋PM2_Supporting) .@*CONCLUSION@#The heterozygous c.3604G>T variant of the EP300 gene probably underlay the RSTS type 2 in this child. Above finding has also expanded the variation spectrum of the EP300 gene.

Clinical features and genetic analysis of two children with Williams-Beuren syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS).@*METHODS@#Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed.@*RESULTS@#Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3；PM2_Supporting).@*CONCLUSION@#Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.

Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses / 中华儿科杂志

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Genetic analysis and prenatal diagnosis of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 due to variants of PIGT gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic etiology of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 (MCAHS3) and provide prenatal diagnosis for her parents.@*METHODS@#A female child who had presented at Linyi People's Hospital on 27 July 2022 for recurrent convulsions for over 4 years was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were taken from the child and her parents and subjected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out on amniotic fluid sample at 18 weeks' gestation. Bioinformatic software was used to analyze the pathogenicity of the protein model for the variant loci.@*RESULTS@#The child was a 4-year-old female with frequent seizures, peculiar facial appearance, hypotonia and severe developmental delay. Genetic analysis revealed that she has harbored compound heterozygous variants of the PIGT gene, namely c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q), which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1126del (p.H376Tfs*56) variant was predicted to be pathogenic (PVS1+PM2_Supporting+PM4), and c.1285G>C (p.E429Q) variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PM4). Prenatal diagnosis suggested that the fetus also harbored the same compound heterozygous variants, and the pregnancy was terminated with induced labor.@*CONCLUSION@#The c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q) compound heterozygous variants of the PIGT gene probably underlay the MCAHS3 in this patient, and prenatal diagnosis has prevented birth of further affected child in this family.

Clinical and genetic analysis of a child with mental retardation autosomal dominant 7 / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and genetic characteristics of a child with clinical manifestations of hypoplasia, epilepsy and abnormal face.@*METHODS@#The clinical data of the child were collected. The peripheral blood samples of the patient and his parents were extracted for high-throughput sequencing, and Sanger sequencing verification and bioinformatics analysis were performed to detect suspected pathogenic variants.@*RESULTS@#The clinical manifestations of the child were overall developmental backwardness, seizures, autism, and special facial appearance. High throughput sequencing showed that there was a heterozygous mutation of exon 11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) of the DYRK1A gene. The same variant was found in neither of her parents, suggesting that it has a denovo origin.@*CONCLUSION@#The exon11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) mutation in DYRK1A gene was the genetic etiology of the case, which enriches the pathogenic gene spectrum of DYRK1A and provides the basis for clinical diagnosis and genetic counseling.

Analysis of three patients with KBG syndrome and epileptic seizures due to variants of ANKRD11 gene / 中华医学遗传学杂志

OBJECTIVE@#To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure.@*METHODS@#Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations.@*CONCLUSION@#Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.

Analysis of ZEB2 gene variation in two patients with Mowat-Wilson syndrome / 中华医学遗传学杂志

OBJECTIVE@#To identify pathogenic variants in two patients with suspected for Mowat-Wilson syndrome (MWS).@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the patients and his family members, and gene variants were analysis by Trio-whole exome sequences and copy number variation sequencing.@*RESULTS@#Patient 1 was found to carried a de novo heterozygous c.2769C>A (p.Y923*) nonsense variant of ZEB2 gene. The variant was not found in his healthy parents and sister. Patient 2 carried a de novo heterozygous frameshift variant of the ZEB2 gene, namely c.315delC (p.A105Afs*3), which has not been previously reported. Both variants were predicted to be pathogenic and can lead to premature occurrence of stop codons.@*CONCLUSION@#The heterozygous c.2769C>A (p.Y923*) and c.315delC (p.A105Afs*3) variants of the ZEB2 gene probably underlay the pathogenesis in the two patients. Gene testing has facilitated confirmation of the diagnosis and genetic counselling.

Myhre Syndrome Misdiagnosed as Marfan Syndrome: an Educational Presentation

Abstract A 32-month-old girl with patent ductus arteriosus, false tendon of left ventricle, mild pulmonary hypertension, and chronic cardiac insufficiency (cardiac function level I-II) was misdiagnosed with Marfan Syndrome and there was no improvement in her physical growth after operation for this disease. The preterm baby was finally diagnosed with Myhre Syndrome by clinical phenotypes and mutation of SMAD4 gene.

Caracterización de pacientes con deformidades faciales / Characterization of patients with facial deformities

Introducción: Las deformidades faciales se expresan como alteraciones métricas perceptibles en la proporción o simetría facial, en desacuerdo con los cánones de belleza y aceptación social históricamente concretos, con repercusión en la psicología del paciente y su entorno. Objetivos: Caracterizar a los pacientes con deformidades faciales de acuerdo al sexo, edad, etiología y localización, así como determinar la relación entre ellas. Método: Las variables estudiadas fueron recogidas durante el examen físico de los pacientes (46), previo consentimiento, vaciadas en una base de datos para su procesamiento, mediante medidas de frecuencias. Para las comparaciones se realizó la prueba exacta de Fisher. Resultados: Predominó el sexo masculino (54,3 por ciento), la etiología traumática con el grupo de edad de 40 - 49 años (19,6 por ciento), el 26,1 por ciento de los pacientes presentaron deformidades de más de una región y no se obtuvieron relaciones estadísticamente significativas en ningunas de las relaciones exploradas. Conclusiones: En los pacientes estudiados prevaleció el sexo masculino, de entre 40 y 49 años, la etiología traumática y localización en una sola región anatómica (AU)

Introduction: Facial deformities are expressed as perceptible metric alterations in facial proportion or symmetry, at odds with historically specific canons of beauty and social acceptance, with repercussions on the psychology of the patient and his or her environment. Objectives: To characterize patients with facial deformities according to sex, age, etiology and location, as well as to determine the relationship between them. Method: The variables studied were collected during the physical examination of the patients (46) with their consent, and were entered into an SPSS Statistics 22 database where statistical processing was carried out with frequency measures. To compare the Fisher's exact test was used. Results: Male sex predominated (54,3 percent ), traumatic etiology with the age group of 40-49 years (19,6 percent), 26,1 percent of the patients presented deformities of more than one region and no statistically significant relationships were obtained in any of the explored relationships. Conclusions: Among the patients studied prevailed male sex, age between 40 and 49 years old, traumatic etiology and located in one anatomical region(AU)

Gender difference in clinical manifestations of KBG syndrome due to variants of ANKRD11 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore gender difference in the clinical manifestations of two children with Keishi-Bukuryo-Gan syndrome (KBGS).@*METHODS@#Clinical manifestations of the two children were reviewed. Genetic testing was carried out through next generation sequencing (NGS). Treatment was summarized, and the prognosis was followed up.@*RESULTS@#Both children showed particular appearance including megatooth, abnormal hair distribution, hands' abnormality and language development delay. NGS revealed that both children have carried pathogenic variants of the ANKRD11 gene (c.1903_1907del and c.4911delT), which resulted in shifting of amino acid sequences starting from the Lysine and Proline at positions 635 and 1638, respectively. The female patient exhibited central precocious puberty. Her height has increased by 13 cm, and sex characteristics has retracted after treatment with leuprorelin for 23 months and recombinant human growth hormone for 1 month.@*CONCLUSION@#Comparison of the two cases with different genders and summary of previously reported cases found that male KBGS patients have more obvious dysmorphisms such as triangular face, synophrys, ocular hypertelorism and vertebral body abnormality, with higher morbidity of epilepsy, mental retardation, autism, congenital heart disease, immune thrombocytopenia and other complications. KBGS is an autosomal dominant disease featuring more evident peculiar appearance and global development delay. Male patients often have multi-system involvement, and multidisciplinary cooperation is required for early recognition of particular features in order to improve the prognosis.

Cardio / 中南大学学报(医学版)

Cardio-facio-cutaneous (CFC) syndrome is an extremely rare autosomal dominant genetic disease due to BRAF and other gene mutations. The main characteristics of the patients are craniofacial deformities, cardiac malformations, skin abnormalities, delay of language and motor development, gastrointestinal dysfunction, intellectual disability, and epilepsy. In this case, the child has a typical CFC syndrome face and developmental delay. The gene results of the second-generation sequencing technology showed that there was a mutation site c.1741A>G (p. Asn581Asp) (heterozygous) in exon 14 of the BRAF (NM_004333.5) gene. The mutation was not observed in the child's parents. The above-mentioned mutation may be a de novo mutation. There is no effective therapy for this disease so far.

Diagnóstico clínico y genético mucolipidosis II - enfermedad células de inclusión / Diagnóstico clínico e genético da mucolipidose II - doença das células de inclusão / Clinical and genetic diagnosis of mucolipidosis II - inclusion cell disease

La Mucolipidosis tipo II es una enfermedad autosómica trastorno recesivo clínicamente caracterizado por la dismorfia facial y una hiperplasia gingival severa. Relato del caso: Se porta caso de paciente de 2 años de edad, con diagnóstico de enfermedad metabólica tipo mucolipidosis II. Al examen físico se encontraron facies tosca, marcada hiperplasia gingival sintomática generalizada en maxilar superior e inferior, encías sangrantes, cuello corto, con regular sostén cefálico, piel delgada, pectus excavatus, codos normales, manos con disminución en el agarre y piel gruesa con xerosis, dificultad para elevar los brazos por encima de la cabeza, retardo global en neurodesarrollo. Por lo cual se manejó el caso de manera multidisciplinaria, permitiendo que el paciente evolucione de manera positiva al tratamiento integral, con mejoramiento en la motricidad. Conclusiones: Los fenotipos clínicos superpuestos son un desafío de diagnóstico para el personal de la salud en Odontología, especialmente en casos de mucolipidosis (ML) y trastornos mucopolisacáridos (MPS), debido a la superposición de las características clínicas

A mucolipidose tipo II é um distúrbio autossômico recessivo caracterizado clinicamente por dismorfia facial e hiperplasia gengival grave. Relato de caso: É relatado o caso de uma paciente de 2 anos com diagnóstico de doença metabólica do tipo mucolipidose II. O exame físico revelou fácies grosseira, hiperplasia gengival sintomática generalizada acentuada na mandíbula superior e inferior, gengivas sangrantes, pescoço curto, com apoio de cabeça regular, pele fina, pectus excavatus, cotovelos normais, mãos com pega diminuída e pele grossa com xerose, dificuldade em levantar os braços acima da cabeça, atraso no desenvolvimento neurológico global. Portanto, o caso foi tratado de forma multidisciplinar, permitindo que o paciente evoluísse de forma positiva para um tratamento integral, com melhora nas habilidades motoras. Conclusões: A sobreposição de fenótipos clínicos é um desafio diagnóstico para o pessoal de saúde em Odontología, especialmente nos casos de mucolipidose (ML) e distúrbios dos mucopolissacarídeos (MPS), devido à sobreposição de características clínicas

Mucolipidosis type II is an autosomal recessive disorder clinically characterized by facial dysmorphia and severe gingival hyperplasia. Case report: The case of a 2-year-old patient with a diagnosis of metabolic disease type mucolipidosis II is reported. Physical examination revealed coarse facies, marked generalized symptomatic gingival hyperplasia in the upper and lower jaw, bleeding gums, short neck, with regular head support, thin skin, pectus excavatus, normal elbows, hands with decreased grip, and thick skin with xerosis, difficulty raising the arms above the head, global neurodevelopmental delay. Therefore, the case was handled in a multidisciplinary way, allowing the patient to evolve in a positive way to comprehensive treatment, with improvement in motor skills. Conclusions: Overlapping clinical phenotypes are a diagnostic challenge for health personnel in Dentistry, especially in cases of mucolipidosis (ML) and mucopolysaccharide disorders (MPS), due to the overlapping of clinical characteristics

Identification of a novel missense variant of the KAT6B gene in a child with Say-Barber-Biesecker-Young-Simpson syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child suspected for Say-Barber-Biesecker-Young-Simpson syndrome.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing was carried out for the proband. Suspected variants were validated by Sanger sequencing. The impact of the variants was predicted by bioinformatic analysis.@*RESULTS@#The child was found to harbor a de novo missense variant c.2623C>T (p.Asp875Tyr) in exon 13 of the KAT6B gene. The variant was previously unreported, and was not recorded in the major allele frequency database and predicted to be pathogenic based on PolyPhen-2, MutationTaster and PROVEAN analysis. As predicted by UCSF chimera and CASTp software, the variant can severely impact the substrate-binding pocket of histone acetyltransferase, resulting in loss of its enzymatic activity. Based on standards and guidelines by the American College of Medical Genetics and Genomics, the variant was classified to be likely pathogenic (PS2+PM2+PP3).@*CONCLUSION@#The child's condition may be attributed to the de novo missense c.2623C>T (p.Asp875Tyr) variant of the KAT6B gene.

Clinical and genetic analysis of a patient with Mowat-Wilson syndrome / 中华医学遗传学杂志

OBJECTIVE@#To summarize the clinical phenotype and genotype of a Chinese child affected with Mowat-Wilson syndrome (MWS).@*METHODS@#Clinical data of the patient were collected. The patient was analyzed by whole-exome sequencing (WES) as well as Sanger sequencing.@*RESULTS@#The patient was a male infant with recurrent fever and slow growth. He also had characteristic facies, recurrent spasm, and growth retardation. WES revealed that he has carried a heterozygous nonsense c.2609C>G (p.Ser870X) variant of the ZEB2 gene (30% mosaicism). Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+PS1+PS2+PM2).@*CONCLUSION@#The c.2609C>G variant of the ZEB2 gene probably underlay the MWS in this child. The mosaicism of the variant may explain his mild symptoms.

Jaffe-Lichtenstein syndrome associated with a simple bone cyst: unprecedented rare case report

Abstract Lesions denominated fibro-osseous lesions of the jaw constitute a diversified group of disorders, in which the normal bone architecture is replaced by fibroblasts, collagen fibers and immature bone. At present, the World Health Organization recognizes four variants of these lesions, namely: bone-cement dysplasia, fibrous dysplasia, ossifying fibroma and Familial gigantiform cementoma. Fibrous dysplasia may present in the monostotic form, affecting one single bone or an isolated craniofacial region; and in the Polyostotic form, involving two or more bones of the skeleton, and eventual association with syndromic conditions. The patient, C.P.G., 43 years old, sought attendance due to symptomatic increase in the region of the mandibular body on the right side. Imaging exams revealed craniofacial areas with ground-glass aspect, beyond the extensive mandibular radiolucent lesion. During the physical exam, spots of the Café au lait type disposed on the right side of the body were identified, in addition to uncoordinated gait with distinct shortening of the right leg. Additional radiographic exams showed evidence of skeletal dissemination of the disease. The patient denied any sexual precocity, and the final diagnosis was fibrous dysplasia, expressed by means of the Jaffe-Lichtenstein syndrome, in association with a simple bone cyst.

Resumo As denominadas lesões fibro-ósseas dos maxilares constituem um grupo diversificado de desordens nas quais a arquitetura óssea normal é substituída por fibroblastos, fibras colágenas e osso imaturo. Atualmente a Organização Mundial de Saúde reconhece quatro variantes destas lesões, sendo elas: a displasia cemento-óssea, a displasia fibrosa, o fibroma ossificante e cementoma gigantiforme familiar. A displasia fibrosa pode ser apresentar na forma monostótica, acometendo um único osso ou a região craniofacial isoladamente, e a forma poliostótica, envolvendo dois ou mais ossos do esqueleto, com eventual associação com condições sindrômicas. Paciente C.P.G., 43 anos, procurou atendimento devido aumento volumétrico sintomático na região de corpo mandibular do lado direito. Exames imaginológicos revelaram áreas craniofaciais com aspecto de vidro fosco ou despolido, além de extensa lesão radiolúcida mandibular. Durante o exame físico foram identificadas manchas do tipo café com leite dispostas do lado direito do corpo, além de marcha descoordenada com nítido encurtamento da perna direita. Novos exames radiográficos evidenciaram a disseminação esquelética da doença. O paciente negou qualquer precocidade sexual e o diagnóstico final foi de displasia fibrosa, expressa por meio da síndrome de Jaffe-Linchtenstein, em associação com um cisto ósseo simples.

General anesthesia for Crisponi syndrome: case report / Anestesia geral para Síndrome de Crisponi: relato de caso

Abstract Crisponi syndrome is a rare and severe heritable disorder characterised by muscle contractions, trismus, apnea, feeding troubles, and unexplained high fever spikes with multiple organ failure. Here we report perioperative care for endoscopic gastrostomy of a 17 month-old female child with Crisponi syndrome. Temperature in the surgery room was strictly monitored and maintained at 19ºC. The patient was exposed to both inhaled and intravenous anesthetic agents. Surgical and perioperative periods were uneventful. Episodes of fever in Crisponi syndrome arise from CRLF1 mutation, which differs from the physiological pathway underlying malignant hyperthermia.

Resumo A Síndrome de Crisponi é uma condição clínica hereditária grave e rara caracterizada por contrações musculares, trismo, apneia, distúrbios na alimentação, picos de febre alta e inexplicável, e falência de múltiplos órgãos. Descrevemos o cuidado perioperatório de paciente pediátrica com 17 meses de idade, portadora da Síndrome de Crisponi, submetida a gastrostomia endoscópica. A temperatura da sala de cirurgia foi cuidadosamente monitorizada e mantida a 19ºC. A paciente foi submetida a agentes anestésicos inalatórios e venosos. O cuidado cirúrgico e perioperatório desenvolveram-se sem incidentes. As crises de febre na Síndrome de Crisponi originam-se de mutação no gene CRLF1, o que as diferenciam do mecanismo fisiopatológico da hipertermia maligna.

Genetic analysis of a rare case of Pitt-Hopkins syndrome due to partial deletion of TCF4 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring delayed intellectual development.@*METHODS@#The child and his parents were subjected to conventional G-banding karyotyping and single nucleotide polymorphism array (SNP-array) analysis. Suspected copy number variations (CNVs) were verified in both parents.@*RESULTS@#No karyotypic abnormality was found with the child and his parents. SNP-array results for both parents were normal. The child was found to harbor a de novo 172 kb deletion at 18q21.2 with a physical position of 52 957 042-53 129 237. The deletion only involved one OMIM gene, namely TCF4, resulting in removal of its exons 6 to 8.@*CONCLUSION@#The SNP-array assay has facilitated with the diagnosis of this child. Deletion of 18q21.2 region probably accounts for the Pitt-Hopkins syndrome (PTHS) in this patient.

Analysis of a case with Mowat-Wilson syndrome caused by ZEB2 gene variant / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a proband with distinctive facial features, global developmental delay, seizures and hypoplasia of corpus callosum through next generation sequencing (NGS).@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Whole exome and flanking sequences were screened by NGS. Suspected variants were verified by Sanger sequencing.@*RESULTS@#The proband was found to carry a heterozygous c.2824G>T (p.G942X) variant of the ZEB2 gene, which was verified by Sanger sequencing to be a de novo variant.@*CONCLUSION@#The heterozygous c.2824G>T (p.G942X) variant of the ZEB2 gene probably underlies the Mowat-Wilson syndrome in the proband.