Expanding the skeletal phenotype of Loeys‐Dietz syndrome

  title={Expanding the skeletal phenotype of Loeys‐Dietz syndrome},
  author={S{\'e}rgio B. Sousa and Karen Lambot-Juhan and Marl{\`e}ne Rio and Genevi{\`e}ve Baujat and Vicken Topouchian and Nadine Hanna and Martine le Merrer and Francis Brunelle and Arnold Munnich and Catherine Boileau and Val{\'e}rie Cormier-Daire},
  journal={American Journal of Medical Genetics Part A},
S ergio B. Sousa, Karen Lambot-Juhan, Marl ene Rio, Genevi eve Baujat, Vicken Topouchian, Nadine Hanna, Martine Le Merrer, Francis Brunelle, Arnold Munnich, Catherine Boileau, and Val erie Cormier-Daire* Department of Medical Genetics (AP-HP), Universit e Paris Descartes, INSERM U781, Hôpital Necker-Enfants Malades, Paris, France Servi co de Gen etica M edica, Hospital Pedi atrico de Coimbra, Coimbra, Portugal Service de Radiologie P ediatrique, Hôpital Necker-Enfants Malades, Paris, France… 

Two Chinese Patients with Loeys-Dietz Syndrome: A Connecitve Tissue Disorder with Marfan-like Features and Vasculopathy

It is of vital importance for paediatricians to recognise this recently described connective tissue disorder in order to provide appropriate surveillance and early intervention to improve the prognosis.

Two Chinese Patients with Loeys-Dietz Syndrome: A Connective Tissue Disorder with Marfan-like Features and Vasculopathy

It is of vital importance for paediatricians to recognise this recently described connective tissue disorder in order to provide appropriate surveillance and early intervention to improve the prognosis.

Hand and fibrillin‐1 deposition abnormalities in Loeys–Dietz syndrome—expanding the clinical spectrum

It is suggested that LDS should be included in the differential diagnosis of joint contractures seen pre and postnatally, because of the lack of fibrillin‐1 microfibril deposition and impaired and inadequate elastic fiber assembly in this patient's fibroblasts.

Arthrogryposis as neonatal presentation of Loeys-Dietz syndrome due to a novel TGFBR2 mutation.

Clinical diagnosis of Larsen syndrome, Stickler syndrome and Loeys-Dietz syndrome in a 19-year old male: a case report

LDS should be considered in patients with a clinical diagnosis of Larsen syndrome, in particular in the presence of arterial aneurysms or tortuosity, and genetic high throughput sequencing analysis is particularly useful for the differential diagnosis of hereditary connective tissue disorders.

Loeys–Dietz syndrome: a primer for diagnosis and management

This review of literature and expert opinion aims to provide medical guidelines for care of individuals with Loeys–Dietz syndrome.

Loeys-Dietz syndrome: cardiovascular, neuroradiological and musculoskeletal imaging findings

This review focuses on the cardiovascular, neuroradiological and musculoskeletal imaging findings in this disorder and recommendations for follow-up imaging.

Evaluation of cervical spine pathology in children with Loeys-Dietz syndrome

Cervical spine evaluation is important in this cohort of children with LDS; 37.5% had evidence of cervical spine instability, and many had concurrent spinal pathology.

High prevalence of cervical deformity and instability requires surveillance in Loeys-Dietz syndrome.

Patients with Loeys-Dietz syndrome have a high prevalence of cervical instability, particularly a pattern of instability at C3 vertebral body hypoplasia and C2-C3 focal kyphosis, and patients requiring surgery typically present in early childhood.



Musculoskeletal findings of Loeys-Dietz syndrome.

Patients with Loeys-Dietz syndrome commonly present to the orthopaedic surgeon with cervical malformations, spinal and foot deformities, and findings in the craniofacial and cutaneous systems.

Recent progress in genetics of Marfan syndrome and Marfan-associated disorders

It is indicated that genetic heterogeneity exists in MFS and its related conditions and that regulation of TGFβ signaling plays a significant role in these disorders.

Aneurysm Syndromes Caused by Mutations in the TGF-β Receptor

An additional cohort of 40 patients who had vascular Ehlers–Danlos syndrome without the characteristic type III collagen abnormalities or the craniofacial features of the Loeys–Dietz syndrome were screened and a mutation in TGFBR1 or TGF BR2 was found.

Aneurysm syndromes caused by mutations in the TGF-beta receptor.

Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan‐related phenotypes

It was indicated that FBN1 mutations were predominant in MFS but TGFBRs defects may account for approximately 5–10% of patients with the syndrome.

TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys‐Dietz syndrome

Several point mutations were found in the highly conserved serine/threonine kinase domain of TGFBR2, which has been shown to be associated with a second type of this disorder with typically mild or absent ocular involvement.

Phenotypic heterogeneity of Marfan-like connective tissue disorders associated with mutations in the transforming growth factor-beta receptor genes.

The findings support the notion that mutations in the TGFBR gene may be associated with greater phenotypic heterogeneity than previously reported and the most probable diagnosis of these 3 patients was LDS.

Two novel and one known mutation of the TGFBR2 gene in Marfan syndrome not associated with FBN1 gene defects

The data support the recently reported association between TGFBR2 gene and MFS without major ocular signs (MFS2), and all patients proven or suspected to be affected by MFS with negative FBN1 gene screening could benefit from rapid investigation of the TGF BR2 gene.

Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype‐phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys‐Dietz syndrome and related disorders

The yield of mutation detection within the two genes was very low : 4.8% for classical MFS, 4.6% for incomplete MFS and 1% for TAAD in the TGFBR2 gene; in contrast to LDS, where the yield was exceptionally high.

A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2

These data definitively implicate perturbation of TGFβ signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.