Dataset Information

Loeys-Dietz syndrome associated with a heterozygous mutation in TGFBR2 in a female infant: A case report.

ABSTRACT: Loeys-Dietz syndrome (LDS) is an unusual hereditary connective tissue disease with no clear standard clinical diagnosis. The present report describes a case of an infant diagnosed with LDS at the age of 2 months and 23 days. To the best of our knowledge, this case represents the youngest reported case of LDS in China. Whole exome sequencing revealed a heterozygous variation, c.1441(exon 6)G>A [p.E481k(p.Glu481Lys) (NM_001024847)], located at chr3:30715708 in the transforming growth factor ? receptor 2 gene. The patient underwent systematic rehabilitation and standard high-risk infant follow-up. Currently, the overall development of the patient continues to improve. The patient can walk with assistance, stand up on her feet unaided, exhibits improved optical line of sight and both eyes can move up and down, side to side (left and right) and track moving objects. The parents have been advised that a further echocardiogram should be performed as soon as possible and regular follow-up sessions with a cardiovascular specialist are ongoing. LDS diagnosis was confirmed in the patient based on collective findings of skeletal system changes, ocular hypertelorism, ocular exotropia, micrognathia and high-vaulted palate, in combination with a specific pathogenic gene mutation.

SUBMITTER: Zhu C

PROVIDER: S-EPMC7678639 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Loeys-Dietz syndrome associated with a heterozygous mutation in <i>TGFBR2</i> in a female infant: A case report.

Zhu Chun C Tong Meiling M Chi Xia X

Experimental and therapeutic medicine 20201104 1

Loeys-Dietz syndrome (LDS) is an unusual hereditary connective tissue disease with no clear standard clinical diagnosis. The present report describes a case of an infant diagnosed with LDS at the age of 2 months and 23 days. To the best of our knowledge, this case represents the youngest reported case of LDS in China. Whole exome sequencing revealed a heterozygous variation, c.1441(exon 6)G>A [p.E481k(p.Glu481Lys) (NM_001024847)], located at chr3:30715708 in the transforming growth factor β rece ...[more]

PMID: 33235621

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Project description:BACKGROUND:Larsen syndrome is a hereditary disorder characterized by osteochondrodysplasia, congenital large-joint dislocations, and craniofacial abnormalities. The autosomal dominant type is caused by mutations in the gene that encodes the connective tissue protein, filamin B (FLNB). Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by arterial aneurysms, dissections and tortuosity, and skeletal, including craniofacial, manifestations. Mutations in five genes involved in the transforming growth factor beta (TGF-?) signaling pathway cause five types of LDS. Stickler syndrome is a genetically heterogeneous arthro-ophthalmopathy caused by defects in collagen, exhibiting a wide specter of manifestations in connective tissue. A rare case is reported that was diagnosed with all these three hereditary connective tissue disorders. CASE PRESENTATION:A 19 year-old, Norwegian male with a clinical diagnosis of Larsen syndrome and with healthy, non-consanguineous parents attended a reference center for rare connective tissue disorders. Findings at birth were hypotonia, joint hypermobility, hyperextended knees, adductovarus of the feet, cervical kyphosis, craniofacial abnormalities, and an umbilical hernia. From toddlerhood, he required a hearing aid due to combined conductive and sensorineural hearing loss. Eye examination revealed hyperopia, astigmatism, and exotropia. At 10 years of age, he underwent emergency surgery for rupture of an ascending aortic aneurysm. At 19 years of age, a diagnostic re-evaluation was prompted by the findings of more distal aortic dilation, tortuosity of precerebral arteries, and skeletal findings. High throughput sequencing of 34 genes for hereditary connective tissue disorders did not identify any mutation in FLNB, but did identify a de novo missense mutation in TGFBR2 and a nonsense mutation in COL2A1 that was also present in his unaffected father. The diagnosis was revised to LDS Type 2. The patient also fulfills the proposed criteria for Stickler syndrome with bifid uvula, hearing loss, and a known mutation in COL2A1. CONCLUSION:LDS should be considered in patients with a clinical diagnosis of Larsen syndrome, in particular in the presence of arterial aneurysms or tortuosity. Due to genetic heterogeneity and extensive overlap of clinical manifestations, genetic high throughput sequencing analysis is particularly useful for the differential diagnosis of hereditary connective tissue disorders.

Project description:BACKGROUND AND PURPOSE:Loeys-Dietz syndrome (LDS) is a recently described entity that has the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Its neuroradiologic manifestations have not been well delineated. We sought to describe the neuroradiologic features of LDS and to assess the manifestations that would warrant follow-up imaging. MATERIALS AND METHODS:Two neuroradiologists retrospectively reviewed CT angiography (CTA), MR imaging, and plain film studies related to the head and neck in 25 patients ranging from 1 to 55 years of age, all of whom had positive genetic testing and clinical characteristics of LDS. Arterial tortuosity was evaluated by subjective assessment of 2D and 3D volumetric CTA and MR angiography data. Craniosynostosis and spinal manifestations were assessed by using plain films and CT images. MR images mostly of the head were reviewed for associated findings such as hydrocephalus, Chiari malformation, etc. Clinical manifestations were collated from the electronic patient record. RESULTS:All patients had extreme arterial tortuosity, which is characteristic of this syndrome. Thirteen patients had scoliosis, 12 had craniosynostosis, 8 had intracranial aneurysms, 6 had spinal instability, 3 had dissections of the carotid and vertebrobasilar arteries, 3 had hydrocephalus, 4 had dural ectasia, 2 had a Chiari malformation, and 1 had intracranial hemorrhage as a complication of vascular dissection. CONCLUSIONS:Significant neuroradiologic manifestations are associated with LDS, predominantly arterial tortuosity. Most of the patients in this series were young and, therefore, may require serial CTA monitoring for development of intra- and extracranial dissections and aneurysms, on the basis of the fact that most of the patients with pseudoaneurysms and dissection were older at the time of imaging. Other findings of LDS such as craniosynostosis, Chiari malformation, and spinal instability may also need to be addressed.

Dataset Information

Loeys-Dietz syndrome associated with a heterozygous mutation in TGFBR2 in a female infant: A case report.

Publications

Loeys-Dietz syndrome associated with a heterozygous mutation in <i>TGFBR2</i> in a female infant: A case report.

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