The first reported case of <scp>Loeys‐Dietz</scp> syndrome in a patient with biallelic <scp><i>SMAD3</i></scp> variants

Baskin, Stephanie M.; Morris, Shaine A.; Vara, Autumn; Hecht, Jacqueline; Farach, Laura S.

doi:10.1002/ajmg.a.61844

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…For both, the scoliotic curve was severe and progressive, driving the indication for surgery. Notably, patient six has a rare homozygous mutation of SMAD3 , causing a severe form of the disease, as previously reported [ 11 ]. Posterior fusion achieves coronal correction of 48-67% in AIS patients [ 22 ], resulting in improved self-reported measures of self-image, function, and level of activity [ 23 ].…”

Section: Discussionsupporting

confidence: 60%

Thoracolumbar Scoliosis in Pediatric Patients With Loeys-Dietz Syndrome: A Case Series

LoPresti¹,

Athukuri²,

Khan³

et al. 2023

Cureus

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BackgroundLoeys-Dietz syndrome (LDS) is a genetic connective tissue disorder that predominantly affects cardiovascular, skeletal, and craniofacial structures. Associated thoracolumbar scoliosis in LDS can be challenging to manage, though other etiologies of pediatric scoliosis have better-defined management guidelines. We examined our institutional experience regarding the treatment of pediatric patients with LDS and scoliosis. MethodologyIn this retrospective study, all patients seen at our pediatric tertiary care center from 2004 through 2018 with a diagnosis of LDS were reviewed, and those with radiographic diagnoses of scoliosis (full-length scoliosis Xrays) were included. Demographic, clinical, and radiographic parameters were collected, and management strategies were reported. ResultsA total of 39 LDS patients whose ages ranged between seven and 13 years were identified. A total of nine patients were radiographically diagnosed with scoliosis, but three patients were excluded due to incomplete medical records, leaving six patients. The median age at scoliosis diagnosis was 11.5 years, with a median follow-up of 51 months. Two patients were successfully managed with observation (average initial Cobb angle (CA): 14°, average final CA: 20.5°). Two were braced, one successfully (initial CA: 15°, final CA: 30°) and one with a progressive disease requiring surgery (initial CA: 40°, final CA: 58°). Of the two who were offered surgical correction, one underwent surgery with a durable correction of spinal deformity (CA: 33° to 19°). One patient underwent a recent correction of aortic root dilatation and was not a candidate for scoliosis surgery. ConclusionsPrinciples of adolescent idiopathic scoliosis management such as bracing for CA of 20-50° and surgery for CA of >50° can be applied to LDS patients with good outcomes. This augments our understanding of the treatment algorithm for pediatric patients with LDS.

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Section: Discussionsupporting

confidence: 60%

Thoracolumbar Scoliosis in Pediatric Patients With Loeys-Dietz Syndrome: A Case Series

LoPresti¹,

Athukuri²,

Khan³

et al. 2023

Cureus

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Siblings with profound connective tissue disease: First report of biallelic TGFBR1‐related Loeys‐Dietz syndrome

Starr

Lindsay

Cárdenas

et al. 2022

American J of Med Genetics Pt A

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Heterozygous missense variants in TGFBR1, encoding one subunit of the transforming growth factor‐beta receptor, are a well‐established cause of Loeys‐Dietz syndrome (LDS)—an autosomal dominant disorder with variable phenotypic expression. Patients with LDS have compromised connective tissues that can result in life‐threatening arterial aneurysms, craniosynostosis, characteristic craniofacial and skeletal anomalies, skin translucency, and abnormal wound healing. We report a full sibship with a biallelic type of TGFBR1‐related disease. Each born at 38 weeks had aortic root dilation, congenital diaphragmatic hernia (CDH), skin translucency, and profound joint laxity at birth. Both had progressive dilation of the aorta and recurrence of a diaphragmatic defect after plication early in infancy. Patient 1 died at 66 days of age and Patient 2 is alive at 4 years and 4 months of age with multiple morbidities including cystic lung disease complicated by recurrent pneumothoraces and ventilator dependence, craniosynostosis, cervical spine instability, progressive dilation of the aorta, worsening pectus excavatum, large lateral abdominal wall hernia, and diffuse aortic ectasia. Fibroblasts cultured from Patient 2 showed decreased TGF‐β responsiveness when compared to control fibroblasts, consistent with previous observations in cells from individuals with autosomal dominant LDS. Whole genome copy number evaluation and sequencing for both patients including their parents as reference revealed compound heterozygous variants of uncertain clinical significance in exon 2 of TGFBR1 (c.239G>A; p.Arg80Gln paternal and c.313C>G; p.His105Asp maternal) in both siblings in trans. Each parent with their respective variant has no apparent medical issues and specifically no LDS characteristics. Neither of these variants have been previously reported. Thousands of patients have been diagnosed with LDS—an established autosomal dominant disease. These siblings represent the first reports of biallelic TGFBR1‐related LDS and expand the differential diagnosis of CDH.

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A Turkish Family with Loeys-dietz Syndrome and a Report of a Homozygous Patient with SMAD3 Pathogenic Variation

Altindas¹,

Zamani²,

Oflaz³

et al. 2022

Haseki

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The first reported case of Loeys‐Dietz syndrome in a patient with biallelic SMAD3 variants

Cited by 3 publications

References 27 publications

Thoracolumbar Scoliosis in Pediatric Patients With Loeys-Dietz Syndrome: A Case Series

Thoracolumbar Scoliosis in Pediatric Patients With Loeys-Dietz Syndrome: A Case Series

Siblings with profound connective tissue disease: First report of biallelic TGFBR1‐related Loeys‐Dietz syndrome

A Turkish Family with Loeys-dietz Syndrome and a Report of a Homozygous Patient with SMAD3 Pathogenic Variation

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