RESUMO
ABSTRACT: Herlyn-Werner-Wunderlich Syndrome is a very rare congenital malformation of the urogenital tract involving both the Mullerian and Wolffian ducts characterized by the triad uterine diadelphys, obstructed vagina, and unilateral renal agenesis. If not diagnosed on time it may progress to adverse gynecological complications making timely diagnosis and treatment crucial. We hereby present a 14-year girl with right flank pain diagnosed as Herlyn-Werner-Wunderlich Syndrome by ultrasound scan which was managed surgically with drainage of hydrocolpos and marsupialization of vaginal septum. On two weeks follow up patient had symptomatic improvement with no any complications.
Assuntos
Hidrocolpos , Ductos Paramesonéfricos , Vagina , Humanos , Feminino , Adolescente , Hidrocolpos/diagnóstico , Hidrocolpos/complicações , Vagina/anormalidades , Vagina/cirurgia , Ductos Paramesonéfricos/anormalidades , Síndrome , Útero/anormalidades , Útero/cirurgia , Anormalidades Múltiplas , Ultrassonografia/métodos , Anormalidades Urogenitais/complicações , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/cirurgia , Ductos Mesonéfricos/anormalidades , Drenagem/métodos , Dor no Flanco/etiologia , Rim/anormalidades , Rim/diagnóstico por imagemRESUMO
OBJECTIVE: Penoscrotal transposition (PST) is a rare anomaly of the external genitalia characterized by malposition of the penis in relation to the scrotum. This transposition may be partial or complete and may be associated with hypospadias, chordee, and other anomalies. We have reviewed our experience with the surgical repair of PST utilizing a modified Glenn-Anderson technique. MATERIALS AND METHODS: Twenty-nine patients with a median age of 5.6 years (8 months -15 years) underwent surgical repair of PST at our institution between 2004-2022. Of those, 20 (69%) had complete PST, while 9 (31%) had partial PST. All children were divided into three groups. In the first group of 8 (28%) children, repair of PST was an integral part of one-stage male genitoplasty; in the second group of 18 (62%) children, repair of PST was an isolated last stage of the staged hypospadias repair and the remaining 3 (10%) children underwent PST repair without the presence of hypospadias. All patients underwent modification of the Glenn-Anderson technique involving utilization of bilateral rotational advancement scrotal flap, complete de-tethering of the testis from the internal part of the scrotum when indicated, and relocation of the scrotal compartment in a normal dependent position. The follow-up ranged from 6 months to 18 years. RESULTS: In the first group, five children (62%) underwent Onlay Prepucial Island Pedicle Flap (OIF) hypospadias repair, and three (38%) underwent Long Tubularized Incised Plate Repair (TIP). In the second group, 8 (44%) underwent OIF hypospadias repair, 2 (12%) had Long TIP repair, and the remaining 8 (44%) underwent staged hypospadias repair. Post-operative Clavien Dindo grade III presented among three patients in group I and only one patient in group II. In the third group, no postoperative complications were observed. CONCLUSION: Our data show that penoscrotal transposition correction utilizing the Glenn-Anderson technique is a reliable and durable surgery in the pediatric population. These children require careful monitoring till adolescence to ensure that no re-operation is needed.
Assuntos
Pênis , Escroto , Procedimentos Cirúrgicos Urológicos Masculinos , Humanos , Masculino , Pré-Escolar , Escroto/cirurgia , Escroto/anormalidades , Lactente , Criança , Adolescente , Pênis/cirurgia , Pênis/anormalidades , Resultado do Tratamento , Estudos Retrospectivos , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Hipospadia/cirurgia , Seguimentos , Fatores de Tempo , Anormalidades Múltiplas , Doenças UretraisAssuntos
Cromossomos Humanos Par 9 , Segundo Trimestre da Gravidez , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Ultrassonografia Pré-Natal/métodos , Cromossomos Humanos Par 9/genética , Adulto , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico por imagem , Análise em Microsséries/métodos , Reação em Cadeia da Polimerase/métodos , Aneuploidia , Aberrações Cromossômicas/embriologiaRESUMO
BACKGROUND: Some chromatinopathies may present with common clinical findings (intellectual disability, brain and limb malformation, facial dysmorphism). Furthermore, one of their cardinal shared features is growth dysregulation.We aimed to assess and deepen this resemblance in three specific conditions, namely Wiedemann-Steiner (WDSTS), Kleefstra (KLEFS1) and Coffin-Siris syndrome (CSS1), with a particular focus on possible metabolic roots. METHODS: Eleven patients were enrolled, three with WDSTS, five with KLEFS1 and three with CSS1, referring to Fondazione IRCCS Ca' Granda Ospedale Maggiore, Milan, Italy. We performed both a physical examination with detailed anthropometric measurements and an evaluation of the patients' REE (rest energy expenditure) by indirect calorimetry, comparing the results with age- and sex-matched healthy controls. RESULTS: We observed new clinical features and overlap between these conditions suggesting that different disturbances of epigenetic machinery genes can converge on a common effect, leading to overlapping clinical phenotypes.The REE was not distinguishable between the three conditions and healthy controls. CONCLUSIONS: Epigenetic machinery plays an essential role both in growth regulation and in neurodevelopment; we recommend evaluating skeletal [craniovertebral junction abnormalities (CVJ) polydactyly], otolaryngological [obstructive sleep apnea syndrome (OSAs), recurrent otitis media], dental [tooth agenesis, talon cusps], and central nervous system (CNS) [olfactory bulbs and cerebellum anomalies] features. These features could be included in monitoring guidelines. Further studies are needed to deepen the knowledge about energy metabolism.
Assuntos
Anormalidades Múltiplas , Face , Deficiência Intelectual , Micrognatismo , Pescoço , Fenótipo , Humanos , Masculino , Feminino , Deficiência Intelectual/genética , Anormalidades Múltiplas/genética , Criança , Micrognatismo/genética , Face/anormalidades , Pré-Escolar , Pescoço/anormalidades , Adolescente , Anormalidades Craniofaciais/genética , Deformidades Congênitas da Mão/genética , Itália , Deleção Cromossômica , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/complicações , Estudos de Casos e Controles , Lactente , Cromossomos Humanos Par 9RESUMO
BACKGROUND: Tinea versicolor is a very common condition. We reported a specific follicular manifestation and proposed that this particular presentation might be related to the patient's history of previous keratosis pilaris. CASE PRESENTATION: A 46-year-old Asian woman of Han ethnicity presented to the clinic with trunk lesions for over a year. On physical examination: multiple light brown patches of varying size centered on hair follicles in the axillae and trunk, with the patches on the back fusing together and scales visible on the surface of the patches. Finally, through fungal microscopy and pathological examination, the patient was diagnosed with folliculocentric tinea versicolor. CONCLUSIONS: Follicular tinea versicolor is a rare type of tinea versicolor. It is still not clear what causes tinea versicolor to become folliculocentric. This case may suggest that patients with a history of keratosis pilaris may have a tendency to develop follicular centration in the course of other diseases.
Assuntos
Tinha Versicolor , Humanos , Feminino , Pessoa de Meia-Idade , Tinha Versicolor/diagnóstico , Tinha Versicolor/tratamento farmacológico , Antifúngicos/uso terapêutico , Folículo Piloso/patologia , Doença de Darier/diagnóstico , Doença de Darier/patologia , Anormalidades Múltiplas , Sobrancelhas/anormalidadesRESUMO
Background: KBG syndrome is a monogenic disorder caused by heterozygous pathogenic variants in ANKRD11. A recent single-case study suggested that the clinical spectrum of KBG syndrome, classically defined by distinctive craniofacial traits and developmental delay, may include movement disorders. Case report: We report a 24-year-old patient harboring a pathogenic de novo ANKRD11 frameshift variant. The phenotype was dominated by a progressive tremor-dominant movement disorder, characterized by rest, intention and postural tremor of the hands, voice tremor, head and tongue tremor, increased muscle tone and signs of ataxia. Additionally, the patient had a history of mild developmental delay and epilepsy. Discussion: Adding to the recently described individual, our present patient highlights the relevance of movement disorders as a clinically relevant manifestation of KBG syndrome. ANKRD11 pathogenic variants should be considered in the differential diagnosis of combined tremor syndromes.
Assuntos
Proteínas Repressoras , Tremor , Humanos , Tremor/genética , Tremor/fisiopatologia , Adulto Jovem , Proteínas Repressoras/genética , Masculino , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Fácies , Mutação da Fase de Leitura , Microcefalia/genética , Microcefalia/complicações , Microcefalia/fisiopatologia , Anormalidades Dentárias/genética , Anormalidades Dentárias/fisiopatologia , Doenças do Desenvolvimento Ósseo/genética , Doenças do Desenvolvimento Ósseo/fisiopatologia , Doenças do Desenvolvimento Ósseo/complicações , Doenças do Desenvolvimento Ósseo/diagnóstico , Feminino , Anormalidades MúltiplasRESUMO
Anorectal malformations (ARMs) consist of a range of anomalies that are often associated with other anomalies The purpose of the study is to assess the incidence of associated congenital anomalies that are seen in patients with ARMs. An observational prospective study was conducted on 162 cases with ARM from February 2019 to January 2020, and data were collected on patient demographics, type of ARM, and associated anomalies using a prestructured questionnaire and analysis done using SPSS (IBM), version 23, software. Relevant statistical analysis was done, and the results are presented in tables and charts. Of 162 cases studied, 70 of them were males and 92 were females with a male-to-female ratio of 0.76:1. The majority of male patients (45%) had rectourethral fistulas, whereas 63% of the females had rectovestibular fistula. While 76 (47%) patients presented with isolated ARM, 86 (53%) had ≥1 associated congenital malformations. Forty-eight (30%) patients presented with a single associated anomaly, whereas 20 (12%) patients had≥3 associated anomalies. The commonest associated anomalies were urologic 26.5% followed by genital (22.8%), cardiac 20.4%, and musculoskeletal 16.6%, and 12.3% of them had vertebral; anorectal; cardiac; tracheoesophageal fistula; renal; limb association. More than half of the children have other associated abnormalities. We found urogenital anomalies to be the most common associated congenital defects. A lower incidence of cardiac and spinal cord anomalies was noted suggesting a need for active workup to be in line with the latest standards of care.
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Malformações Anorretais , Humanos , Masculino , Feminino , Estudos Prospectivos , Malformações Anorretais/epidemiologia , Malformações Anorretais/complicações , Incidência , Recém-Nascido , Pobreza/estatística & dados numéricos , Anormalidades Múltiplas/epidemiologia , Índia/epidemiologia , Lactente , Criança , Pré-Escolar , Fístula Retal/epidemiologiaRESUMO
BACKGROUND: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA. METHODS: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping. The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trio-WGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. RESULTS: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants. There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants. CONCLUSION: This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS.
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Anormalidades Múltiplas , Cariotipagem , Sequenciamento Completo do Genoma , Humanos , Recém-Nascido , Estudos Prospectivos , Masculino , Feminino , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Fenótipo , Unidades de Terapia Intensiva Neonatal , Lactente , Genótipo , Testes Genéticos/métodosRESUMO
The 22q11.2 region is highly susceptible to genomic rearrangements leading to multiple genomic disorders, including 22q11.2 microdeletion syndrome (22q11.2 DS) (MIM# 188400), 22q11.2 microduplication syndrome (MIM# 608363), supernumerary der(22)t(11;22) syndrome (also known as Emanuel Syndrome; MIM# 609029), and Cat Eye Syndrome (MIM# 115470). In this study, we present data on causes of mortality, average age of death, and the existing associated risk factors in patients with 22q11.2 rearrangements. Our cohort included 223 patients (120 males and 103 females) with confirmed diagnoses of 22q11.2 rearrangements diagnosed through molecular techniques (FISH, MLPA, and CMA). Relatives from patients who have been molecularly confirmed with 22q11.2 rearrangements have also been added to the study, regardless of the presence or absence of symptoms. Of these 223 individuals, 21 (9.4%) died. Deceased patients' rearrangements include 19 microdeletions, 1 microduplication, and 1 patient with a marker chromosome. The median age of death was 3 months and 18 days (ranging from 3 days to 34 years). There were 17 patients who died at pediatric age (80.95%), 3 died at adult age (14.28%), and for 1 of whom, the age of death is unknown (4.76%). Eighteen patients were White Mediterranean (European non-Finnish) (85.71%) whereas three were Amerindian (South American) (14.28%). Mortality from cardiac causes accounted for 71.42%. The second most frequent cause of death was sepsis in two patients (9.52%). One patient died from respiratory failure (4.76%) and one from renal failure (4.76%). Information regarding the cause of death was not available in two patients (9.52%). Most patients who died were diagnosed within the first week of life, the majority on the first day. This study adds additional information on mortality in one of the largest cohorts of patients with 22q11.2 rearrangements in more than 30 years of follow-up.
Assuntos
Cromossomos Humanos Par 22 , Síndrome de DiGeorge , Humanos , Masculino , Feminino , Lactente , Cromossomos Humanos Par 22/genética , Pré-Escolar , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/mortalidade , Criança , Recém-Nascido , Adolescente , Duplicação Cromossômica/genética , Adulto , Adulto Jovem , Anormalidades MúltiplasRESUMO
Bruck syndrome is a rare, autosomal-recessive condition associated with features of both arthrogryposis and osteogenesis imperfecta. It is characterised by congenital large joint contractures with pterygia and bone fragility, leading to fractures and deformities, along with a short stature caused by progressive skeletal deformities. There are fewer than 50 described cases of Bruck syndrome in the literature, with no reported cases in pregnancy. We describe a case of a successful pregnancy in a woman with Bruck syndrome.In pregnant women with Bruck syndrome, we recommend a multidisciplinary approach including input from obstetric and fetal medicine specialists, midwives, anaesthetists, geneticists, occupational therapists and physiotherapists.
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Artrogripose , Osteogênese Imperfeita , Humanos , Feminino , Gravidez , Artrogripose/diagnóstico , Osteogênese Imperfeita/complicações , Osteogênese Imperfeita/diagnóstico , Adulto , Complicações na Gravidez/diagnóstico , Anormalidades Múltiplas/diagnóstico , Resultado da Gravidez , Hipertermia Maligna , Anormalidades da PeleRESUMO
Background: Wiedemann-Steiner syndrome (WSS), a rare autosomal-dominant disorder caused by haploinsufficiency of the KMT2A gene product, is part of a group of disorders called chromatinopathies. Chromatinopathies are neurodevelopmental disorders caused by mutations affecting the proteins responsible for chromatin remodeling and transcriptional regulation. The resulting gene expression dysregulation mediates the onset of a series of clinical features such as developmental delay, intellectual disability, facial dysmorphism, and behavioral disorders. Aim of the Study: The aim of this study was to investigate a 10-year-old girl who presented with clinical features suggestive of WSS. Methods: Clinical and genetic investigations were performed. Whole exome sequencing (WES) was used for genetic testing, performed using Illumina technology. The bidirectional capillary Sanger resequencing technique was used in accordance with standard methodology to validate a mutation discovered by WES in all family members who were available. Utilizing computational protein modeling for structural and functional studies as well as in silico pathogenicity prediction models, the effect of the mutation was examined. Results: WES identified a de novo heterozygous missense variant in the KMT2A gene KMT2A(NM_001197104.2): c.3451C>G, p.(Arg1151Gly), absent in the gnomAD database. The variant was classified as Likely Pathogenetic (LP) according to the ACMG criteria and was predicted to affect the CXXC-type zinc finger domain functionality of the protein. Modeling of the resulting protein structure suggested that this variant changes the protein flexibility due to a variation in the Gibbs free energy and in the vibrational entropy energy difference between the wild-type and mutated domain, resulting in an alteration of the DNA binding affinity. Conclusions: A novel and de novo mutation discovered by the NGS approach, enhancing the mutation spectrum in the KMT2A gene, was characterized and associated with WSS. This novel KMT2A gene variant is suggested to modify the CXXC-type zinc finger domain functionality by affecting protein flexibility and DNA binding.
Assuntos
Sequenciamento do Exoma , Histona-Lisina N-Metiltransferase , Proteína de Leucina Linfoide-Mieloide , Humanos , Feminino , Sequenciamento do Exoma/métodos , Proteína de Leucina Linfoide-Mieloide/genética , Criança , Histona-Lisina N-Metiltransferase/genética , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Deficiência Intelectual/diagnóstico , Mutação de Sentido Incorreto , Anormalidades Múltiplas/genéticaRESUMO
Not required for Clinical Vignette.
Assuntos
Hormônio do Crescimento Humano , Micrognatismo , Humanos , Hormônio do Crescimento Humano/uso terapêutico , Masculino , Micrognatismo/tratamento farmacológico , Deformidades Congênitas da Mão/tratamento farmacológico , Deformidades Congênitas da Mão/genética , Resultado do Tratamento , Anormalidades Múltiplas/tratamento farmacológico , Anormalidades Múltiplas/genética , Deficiência Intelectual/tratamento farmacológico , Pescoço/anormalidades , Face/anormalidades , Proteínas Recombinantes/uso terapêuticoRESUMO
OBJECTIVE: To analyze the lymphocyte subsets in individuals with Kabuki syndrome for better characterizing the immunological phenotype of this rare congenital disorder. METHODS: We characterized the immunological profile including B-, T- and natural killer-cell subsets in a series (N = 18) of individuals with Kabuki syndrome. RESULTS: All 18 individuals underwent genetic analysis: 15 had a variant in KMT2D and 3 a variant in KDM6A. Eleven of the 18 individuals (61%) had recurrent infections and 9 (50%) respiratory infections. Three (17%) had autoimmune diseases. On immunological analysis, 6 (33%) had CD4 T-cell lymphopenia, which was preferentially associated with the KMT2D truncating variant (5/9 individuals). Eight of 18 individuals (44%) had a humoral deficiency and eight (44%) had B lymphopenia. We found abnormal distributions of T-cell subsets, especially a frequent decrease in recent thymic emigrant CD4 + naive T-cell count in 13/16 individuals (81%). CONCLUSION: The immunological features of Kabuki syndrome showed variable immune disorders with CD4 + T-cell deficiency in one third of cases, which had not been previously reported. In particular, we found a reduction in recent thymic emigrant naïve CD4 + T-cell count in 13 of 16 individuals, representing a novel finding that had not previously been reported.
Assuntos
Anormalidades Múltiplas , Proteínas de Ligação a DNA , Face , Histona Desmetilases , Proteínas de Neoplasias , Doenças Vestibulares , Humanos , Doenças Vestibulares/genética , Doenças Vestibulares/imunologia , Face/anormalidades , Feminino , Masculino , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/imunologia , Criança , Proteínas de Ligação a DNA/genética , Adolescente , Histona Desmetilases/genética , Pré-Escolar , Adulto , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Adulto Jovem , Lactente , Linfopenia/imunologia , Linfopenia/genética , Fenótipo , Doenças Hematológicas/genética , Doenças Hematológicas/imunologia , Mutação , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , ImunofenotipagemRESUMO
Genetic variants in the zone of polarizing activity regulatory sequence (ZRS) that induce ectopic expression of the SHH gene have been associated with different ZRS-related phenotypes. We report the first patient with a de novo variant, c.423+4916 T>C, in ZRS (previously classified as a variant of uncertain significance) that causes tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome (THPTTS). A two-month-old male patient presented with bilateral preaxial polydactyly, triphalangeal thumb, and tibial agenesis and was heterozygous for the variant c.423+4916T>C (neither of his parents was a carrier). The findings obtained from the family study were sufficient to reclassify the variant from "uncertain significance" to "likely pathogenic" according to three criteria from the American College of Medical Genetics and Genomics guidelines, as follows: (1) absence of gnomAD, (2) confirmation of paternity and maternity, and (3) strong phenotype-genotype association. In ZRS-associated syndromes, a wide clinical spectrum has been observed, ranging from polydactyly to THPTTS; our patient has the most severe and rare phenotype. We did not perform functional assays. However, the c.423+4916T>C variant is flanked by three variants, which have been proven not only to cause the phenotype but also to increase the expression of SHH. Through all this data gathering, we consider the c.423+4916T>C variant to be causative of THPTTS.
Assuntos
Ectromelia , Deformidades Congênitas da Mão , Polegar , Humanos , Lactente , Masculino , Anormalidades Múltiplas/genética , Anormalidades Congênitas , Ectromelia/genética , Estudos de Associação Genética , Deformidades Congênitas da Mão/genética , Proteínas Hedgehog/genética , Disostose Mandibulofacial , Mutação , Fenótipo , Polidactilia/genética , Polegar/anormalidades , Tíbia/anormalidades , Dedos do Pé/anormalidadesRESUMO
Pulmonary agenesis is a very rare congenital abnormality that can be missed in a routine radiographic examination, which delays diagnosis until adulthood. It can be associated with other congenital malformations, such as valvular heart disease and gastrointestinal organ abnormalities. Computed tomography (CT) is a useful modality for its better delineation of pulmonary and vascular structures. The reported case here is for an adult male who presented with dextroposition of the heart and was found to have a unilobed right lung associated with polysplenia. This has not been previously reported in the literature.
Assuntos
Pulmão , Baço , Tomografia Computadorizada por Raios X , Humanos , Masculino , Pulmão/anormalidades , Pulmão/diagnóstico por imagem , Baço/anormalidades , Baço/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Anormalidades Múltiplas/diagnóstico por imagem , AdultoRESUMO
BACKGROUND: Contiguous gene deletion in the short arm of chromosome 4 is linked to various neurodevelopmental disorders. METHODS: In this study, we conducted peripheral blood chromosome G-banding karyotyping and whole-exome sequencing (WES) on a proband presenting with anal atresia, global developmental delay, lymphocytosis, and other multisystem anomalies. Additionally, chromosome G-banding karyotyping was also carried out on the proband's parents and brother. RESULTS: The 7-month-old proband was found to have a 26.738 Mb 4p15.33-p14 deletion as identified by chromosome G-banding karyotyping and WES. CONCLUSION: We identified a patient with proximal 4p deletion syndrome by karyotype and WES analysis, which might explain some of his phenotypes. Our research enhances clinicians' knowledge of this rare condition, and offers valuable genetic counseling to the affected family. Further research is necessary to identify the causative gene or critical region associated with proximal 4p deletion syndrome.
Assuntos
Anormalidades Múltiplas , Deleção Cromossômica , Cromossomos Humanos Par 4 , Humanos , Masculino , Lactente , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Cromossomos Humanos Par 4/genética , Fenótipo , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Cariotipagem , Sequenciamento do ExomaRESUMO
OBJECTIVE: To explore the genetic etiology of a fetus with Coffin-Siris syndrome (CSS). METHODS: A fetus with abnormal ultrasound findings detected at Luoyang Maternal and Child Health Care Hospital in July 2023 was selected as the study subject. Clinical data were analyzed retrospectively. Whole exome sequencing was carried out on fetal tissue and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and pathogenicity analysis. This study was approved by the Luoyang Maternal and Child Health Care Hospital (Ethics No. LYFY-YCCZ-2023011). RESULTS: Color Doppler ultrasound at 16+ gestational weeks revealed bilateral ventriculomegaly and cerebellar hypoplasia in the fetus. Trio-WES found that the fetus has harbored a heterozygous c.553C>T (p.Gln185Ter) variant of the ARID1A gene, which was verified by Sanger sequencing to have a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.553C>T (p.Gln185Ter) variant of the ARID1A gene was classified as pathogenic (PVS1+PS2_Supporting+PM2_Supporting). CONCLUSION: The fetus was diagnosed with CSS type 2, and the heterozygous c.553C>T (p.Gln185Ter) variant of the ARID1A gene probably underlay its brain malformations.
Assuntos
Anormalidades Múltiplas , Proteínas de Ligação a DNA , Face , Deformidades Congênitas da Mão , Deficiência Intelectual , Micrognatismo , Pescoço , Fatores de Transcrição , Humanos , Micrognatismo/genética , Fatores de Transcrição/genética , Face/anormalidades , Deformidades Congênitas da Mão/genética , Feminino , Pescoço/anormalidades , Gravidez , Proteínas de Ligação a DNA/genética , Deficiência Intelectual/genética , Anormalidades Múltiplas/genética , Deformidades Congênitas das Extremidades Superiores/genética , Feto/anormalidades , Adulto , Sequenciamento do Exoma , Mutação , Testes Genéticos , Ultrassonografia Pré-Natal , Diagnóstico Pré-NatalRESUMO
To our knowledge, this is the first report of a patient with both genetically confirmed Kabuki and Marfan syndrome demonstrating a perifoveal macular degeneration in one eye. Progressive loss of the outer retinal layers was captured and demonstrated with spectral-domain optical coherence tomography imaging. Fundus autofluorescence imaging revealed perifoveal hypoautofluorescence. The patient had initially presented with a spontaneously resolved serous-exudative retinal detachment associated with tortuous retinal vasculature and preretinal proliferative vitreoretinopathy in the other eye. Prior to presentation, the patient had an ocular history of bilateral ectopia lentis treated with crystalline lens removal and placement of iris-claw intraocular lenses. [Ophthalmic Surg Lasers Imaging Retina 2024;55:541-544.].
Assuntos
Degeneração Macular , Síndrome de Marfan , Descolamento Retiniano , Tomografia de Coerência Óptica , Humanos , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Degeneração Macular/diagnóstico , Degeneração Macular/etiologia , Degeneração Macular/complicações , Tomografia de Coerência Óptica/métodos , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/complicações , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/etiologia , Angiofluoresceinografia/métodos , Anormalidades Múltiplas/diagnóstico , Face/anormalidades , Acuidade Visual , Feminino , Masculino , Fundo de Olho , Progressão da DoençaRESUMO
Macrophage activation syndrome (MAS), is a severe and fatal complication of various pediatric inflammatory disorders. Kabuki syndrome (KS), mainly caused by lysine methyltransferase 2D (KMT2D; OMIM 602113) variants, is a rare congenital disorder with multi-organ deficiencies. To date, there have been no reported cases of MAS in patients with KS. This report describes a case of a 22-year-old male with Kabuki syndrome (KS) who developed MAS. This unique case not only deepens the understanding of the involvement of KMT2D in immune regulation and disease, but expands the phenotype of the adult patient to better understand the natural history, disease burden, and management of patients with KS complicated with autoimmune disorders.