Neonatal Marfan Syndrome: Report of a Case with an Inherited Splicing Mutation outside the Neonatal Domain.
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SUBMITTER: Le Gloan L
PROVIDER: S-EPMC4802997 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMarfan syndrome (MFS) is a heritable disorder of connective tissue resulting from pathogenic variants of the fibrillin-1 gene (FBN1). Neonatal Marfan syndrome (nMFS) is rare and the most severe form of MFS, involving rapidly progressive cardiovascular dysfunction leading to death during early childhood. The constant enrichment of the nMFS mutation spectrum is helpful to improve our understanding of genotype-phenotype correlations in the disease. Herein, we report a novel dominant mutation in exon 26 of FBN1 (c.3331 T > C) in a sporadic case with nMFS.Case presentationAn 8-month-old Han Chinese girl presented with the classic nMFS phenotype, including prominent manifestations of bone overgrowth, aortic root dilatation, and multiple cardiac valve dysfunctions. Genetic analysis revealed that she was heterozygous for a de novo FBN1 missense mutation (c.3331 T > C). The mutation leads to the substitution of a highly conserved FBN1 cysteine residue (p.Cys1111Arg), which is likely to severely perturb the FBN1 structure because of an alteration of the disulfide bond pattern in the calcium-binding epidermal growth factor-like (cbEGF) 12 domain. This variant was absent in 208 ethnically matched controls, providing further evidence that it may be causative of nMFS. An analysis of nMFS-associated mutations from the UMD-FBN1 database indicates that those de novo mutations altering disulfide bonds or Ca(2+) binding sites of the cbEGF domains encoded by exons 25-33, and a lack of phenotypic heterogeneity may be associated with an increased risk for nMFS.ConclusionWe diagnosed an infant with rare nMFS showing rapidly progressive cardiovascular dysfunction and widely systemic features. As the only causal FBN1 mutation identified in the patient, the missense mutation c.3331 T > C (p.Cys1111Arg) was associated with the severe phenotype of MFS. However, the pathogenicity of the novel mutation needs further confirmation in other patients with nMFS. Our review of the prominent characteristics of nMFS mutations relative to classic or incomplete MFS-related mutations will be helpful for the recognition of novel nMFS-associated variants.
| S-EPMC4852411 | biostudies-literature
Project description:BackgroundPersistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia.Patient presentationWe report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported.ConclusionsKabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.
| S-EPMC7499940 | biostudies-literature
Project description:Neonatal Marfan syndrome (nMFS) is considered to be on the most severe end of the spectrum of type I fibrillinopathies. The common features of nMFS include ascending aortic dilatation, severe mitral and/or tricuspid valve insufficiency, ectopia lentis, arachnodactyly, joint contractures, crumpled ear, loose skin, and pulmonary emphysema.We describe a newborn male diagnosed with nMFS. He presented several atypical features, such as diaphragmatic eventration, severe hydronephrosis with hydroureter, and dilated cisterna magna. Molecular analysis revealed a missense mutation at nucleotide 3217 (c.3217G>A) in exon 26 of the fibrillin-1 (FBN1) gene, resulting in the substitution of a glutamate for a lysine at codon 1073 (E1073K) in the 12th calcium binding epidermal growth factor-like domain of the FBN1 protein. Here we report a rare case of Nmfs with several combined atypical features, such as diaphragmatic eventration, severe hydronephrosis with hydroureter, and dilated cisterna magna. Our report is the first atypical nMFS case with p.Glu1073Lys mutation of FBN1 in Korea and may help clinicians with the diagnosis and follow-up of atypical nMFS.
| S-EPMC5143279 | biostudies-literature
Project description:BackgroundNeonatal Marfan syndrome (nMFS), the most severe form of Marfan syndrome, is a rare condition that presents a clinical and treatment challenge. nMFS has high infant mortality related to progressive valvular dysfunction. Valve replacement in this setting improves long-term prognosis but carries high morbidity and mortality. Thus, sharing clinical experience in treating such patients is valuable.Case summaryA 2 year old with nMFS underwent tricuspid valve annuloplasty and prosthetic mitral valve replacement. Postoperative management was complicated by pulmonary hypertension, cardiogenic shock, and arrythmias. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) helped overcome these challenges but posed a high risk for prosthetic valve thrombosis (PVT). Despite decompression of the left atrium (LA) with an LA vent, the left ventricle (LV) was distended because of aortic regurgitation and no native cardiac output. We lowered the ECMO flow under echocardiographic guidance; used inodilators and pacing to encourage transmitral flow and reduce LV afterload. The patient completed a successful 6-day ECMO run with good end-organ perfusion. At last follow up, she was 6 years old, enjoying school, home-ventilated through the tracheostomy, and mobilizing with walking aids/wheelchair.DiscussionValve replacement can improve life quality and expectancy for patients with nMFS. Lowering ECMO flow under echocardiography guidance till the aortic valve is seen to open; coupled with inodilators, pacing and adequate anticoagulation can be a safe way to deliver VA-ECMO for cardiogenic shock after prosthetic valve replacement. Further research is needed to show if this strategy prevents prosthetic valve thrombosis and provides sufficient haemodynamic support and myocardial rest.
| S-EPMC9477202 | biostudies-literature
Project description:RationaleKBG syndrome (KBGS, OMIM: 148050), a rare genetic disorder, is clinically characterized by megalodontia, short stature, skeletal abnormalities, and nervous system manifestations. In the study, we explore the clinical and genetic characteristics of one neonate suffering KBGS caused by ANKRD11 gene mutation.Patient concernsThe proband, a female, was born prematurely at 31 + 2 weeks. There were repeated infections and abdominal distension in the first month after birth, and the platelets could not rise to normal. Head ultrasound showed intracranial brain injury and intracranial hemorrhage.DiagnosesSequencing revealed that there was a heterozygous mutation in exon 9 of the ANKRD11 gene (NM_013275.5) for the child, c.1896_1897delTA (p.H632Qfs*30), which was a de novo mutation and has not been reported. Combining clinical features and genetic results, the proband was diagnosed as KBGS.Interventions and outcomesThe brain sonography on day 4 after birth showed brain injury and intracranial hemorrhage. Therefore, 140 mg of bovine lung surfactant was administered through endotracheal intubation in addition to ventilator-assisted ventilation. Antibiotic treatment was also given till the inflammatory indicators of the infant returned to normal levels. The following-up of 1-year-6-month showed that the language, motion and height of development is slight falling behind the children of the same age.LessonsThis is the first case of KBGS was diagnosed in the neonatal period, which provides a reference for the child to receive timely and correct treatment.
| S-EPMC10553122 | biostudies-literature
Project description:Marfan syndrome (MFS) is a genetic disorder of the connective tissue which rarely manifests in the neonatal period and has an ominous prognosis. A case of a first female offspring of healthy parents is described here. The pregnancy was uneventful and the mother had a term caesarean delivery. At birth, some dysmorphic signs became apparent, such as loose redundant skin, dolichocephaly, frontal bossing, deeply sunken eyes, micrognathia, contractures of the elbows, arachnodactyly and hip dysplasia. The echocardiogram showed a mitral and tricuspid valve regurgitation and a long aortic arch. The diagnosis of neonatal MFS came forward and genetic studies revealed a de novo mutation in the fibrillin 1 (FBN1) gene. At 6 months, due to a progressive worsening of the cardiac pathology, she was submitted to mitral valvuloplasty. She is now 2 years and 10 months old, which is a remarkable feat for a child suffering from this condition.
| S-EPMC4069814 | biostudies-literature
Project description:The study's purpose is to investigate the clinical characteristics and research progress of PURA syndrome. It will also provide new ideas and methods for the diagnosis of neonatal hypotonia etiology. A case of PURA syndrome admitted to Shenzhen Hospital of Peking University was analyzed retrospectively. The keywords "PURA", "PURα", "PURA syndrome", and "5q31" were used to search the Chinese periodical full-text database and Wanfang database. The keywords "PURA", "PURα", "Pur-alpha", "PURA syndrome", and "5q31" were used to search the biomedical literature database (PubMed). The Web of Science database and Proquest database were used to find works of literature from the establishment of the database to November 10, 2019. By analyzing the 72 cases of PURA syndrome reported in ten Chinese and international studies, it was found that 57% (21/37) of the patients had a gestational age greater than 41 weeks. Neonatal patients exhibited hypotonia (82%, 59/72), feeding difficulties (97%, 64/66), apnea or primary hypoventilation (57%, 41/72), intrauterine excessive hiccupping (55%, 6/11), and drowsiness (51%, 24/47). After the neonatal period, the pediatric patients demonstrated moderate to severe mental retardation (100%), epilepsy (54%, 29/54), progressive hip dysplasia (17%, 7/42), scoliosis (48%, 11/23), dysphagia and salivation (69%, 25/36), and constipation (60%, 21/35). The clinical manifestations of the present case were consistent with those in the literature reports. It was the first confirmed case at Shenzhen Hospital in the neonatal period and had a de novo mutation. It was difficult to diagnose PURA syndrome in the neonatal period, which might affect multiple systems. In newborns with obvious hypotonia, the evaluation should be expanded to consider other symptoms. Additionally, targeted gene detection should be completed to achieve early diagnosis and intervention, improve the prognosis, and perform genetic counseling.
| S-EPMC7882292 | biostudies-literature
Project description:The Witkop syndrome is a rare autosomal dominant disorder characterized by the absence of several teeth and abnormalities of the nails. This is the first report of a rare genetic tooth and nail syndrome diagnosed in a 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia. A homozygous mutation was identified in 3'-UTR of MSX1 gene in the proband. The parents of the patient had no dental and nail anomalies.
| S-EPMC3771223 | biostudies-literature
Project description: Not available
| S-EPMC10964307 | biostudies-literature
Project description:RationaleBranchiooculofacial syndrome (BOFS) is a rare autosomal dominant disorder with a diverse clinical phenotype. To summarise the clinical characteristics and genetic variations of neonatal-onset BOFS through a case study and literature review.Patient concernsA preterm neonate with a very low birth weight, born at a gestational age of 29+3 weeks, exhibited cosmetic abnormalities at a postmenstrual age of 34+6 weeks, including microcleft lip, high arched palate, curved upper lip, low ear position, and ocular hypertelorism. Hence, a genetic test on peripheral blood was carried out.DiagnosesThe genetic testing showed a heterozygous variant of c.724G > A (p.Glu242Lys) in the exon 4 region of the TFAP2A (transcription factor AP-2-α) gene in the short arm of chromosome 6. BOFS was confirmed based on clinical appearance and the genetic result.InterventionsThe patient underwent solely cleft lip repair at the age of 6 months with no further intervention.OutcomesThe infant shows normal growth and development at 1 year of age and subsequent follow-up.LessonsThe characteristic facial features, branchial skin defects, and ocular anomalies are the main clinical manifestations of BOFS with neonatal onset, but the diverse clinical phenotype and variable genetic variants pose certain challenges for clinical diagnosis.
| S-EPMC10627626 | biostudies-literature