Spondylocarpotarsal synostosis syndrome. A rare case of short stature and congenital scoliosis

Mangaraj, Swayamsidha; Choudhury, A. K.; M, Sar; Patro, Debasish

doi:10.11138/ccmbm/2017.14.2.258

Cited by 3 publications

(7 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These conditions have been reported in less than 25% reported cases [ 1 , 6 , 14 ]. Rarely, rib anomalies, odontoid aplasia and epiphyseal dysplasia with SCT are also present [ 1 , 2 , 15 ]. None of these conditions were manifested by our patients.…”

Section: Discussionmentioning

confidence: 99%

“…Other skeletal deformities include clinodactyly, brachydactyly, limited joint mobility, cleft palate and dysmorphic facial features. Patients with SCT can exhibit dental enamel hypoplasia and mixed hearing loss [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Filamins arrange actin into three dimensional networks and control structure and function of cytoskeleton. Filamin B, encoded by FLNB is involved in cartilage growth and condensation of developing vertebrae [ 2 ]. FLNB is composed of two actin-binding domains (ABD) at the N-terminus and 24 filamin repeat regions.…”

Section: Introductionmentioning

confidence: 99%

“…SCT can be inherited due to MYH3 variant , or predominantly by biallelic loss of function alleles of FLNB [ 1 , 4 ]. Interestingly, heterozygous missense variants of FLNB cause different autosomal dominant syndromes which include Boomerang dysplasia (BD; OMIM # 112310), Larsen syndrome (LS; OMIM # 150250), Atelosteogenesis I (AOI; OMIM # 108720) and III (AOIII; OMIM # 108721) [ 2 ]. Less than 20 families having patients with FLNB -related SCT are known [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report

Yasin

Mäkitie

Naz

2021

BMC Musculoskelet Disord

View full text Add to dashboard Cite

Background Loss of function or gain of function variants of Filamin B (FLNB) cause recessive or dominant skeletal disorders respectively. Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive disorder characterized by short stature, fused vertebrae and fusion of carpal and tarsal bones. We present a novel FLNB homozygous pathogenic variant and present a carrier of the variant with short height. Case presentation We describe a family with five patients affected with skeletal malformations, short stature and vertebral deformities. Exome sequencing revealed a novel homozygous frameshift variant c.2911dupG p.(Ala971GlyfsTer122) in FLNB, segregating with the phenotype in the family. The variant was absent in public databases and 100 ethnically matched control chromosomes. One of the heterozygous carriers of the variant had short stature. Conclusion Our report expands the genetic spectrum of FLNB pathogenic variants. It also indicates a need to assess the heights of other carriers of FLNB recessive variants to explore a possible role in idiopathic short stature.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report

Yasin

Mäkitie

Naz

2021

BMC Musculoskelet Disord

View full text Add to dashboard Cite

show abstract

“…Spondylocarpotarsal synostosis (SCT) is an autosomal recessive skeletal disorder characterized by carpal/tarsal bone and vertebrae fusions, delayed endochondral ossification, and short stature 1 – 6 . The majority of SCT cases result from biallelic nonsense mutations in the gene that encodes filamin B ( FLNB ) 2 , 5 – 7 . SCT is progressive; there is radiographic evidence of mild disc narrowing at birth ultimately advancing to severe spinal scoliosis, kyphosis, and lordosis due to premature vertebral fusions 1 , 2 , 5 , 6 , 8 .…”

Section: Introductionmentioning

confidence: 99%

Intervertebral disc degeneration is rescued by TGFβ/BMP signaling modulation in an ex vivo filamin B mouse model

Zieba¹,

Forlenza²,

Heard³

et al. 2022

Bone Res

View full text Add to dashboard Cite

Spondylocarpotarsal syndrome (SCT) is a rare musculoskeletal disorder characterized by short stature and vertebral, carpal, and tarsal fusions resulting from biallelic nonsense mutations in the gene encoding filamin B (FLNB). Utilizing a FLNB knockout mouse, we showed that the vertebral fusions in SCT evolved from intervertebral disc (IVD) degeneration and ossification of the annulus fibrosus (AF), eventually leading to full trabecular bone formation. This resulted from alterations in the TGFβ/BMP signaling pathway that included increased canonical TGFβ and noncanonical BMP signaling. In this study, the role of FLNB in the TGFβ/BMP pathway was elucidated using in vitro, in vivo, and ex vivo treatment methodologies. The data demonstrated that FLNB interacts with inhibitory Smads 6 and 7 (i-Smads) to regulate TGFβ/BMP signaling and that loss of FLNB produces increased TGFβ receptor activity and decreased Smad 1 ubiquitination. Through the use of small molecule inhibitors in an ex vivo spine model, TGFβ/BMP signaling was modulated to design a targeted treatment for SCT and disc degeneration. Inhibition of canonical and noncanonical TGFβ/BMP pathway activity restored Flnb−/− IVD morphology. These most effective improvements resulted from specific inhibition of TGFβ and p38 signaling activation. FLNB acts as a bridge for TGFβ/BMP signaling crosstalk through i-Smads and is key for the critical balance in TGFβ/BMP signaling that maintains the IVD. These findings further our understanding of IVD biology and reveal new molecular targets for disc degeneration as well as congenital vertebral fusion disorders.

show abstract

Novel FLNB Variants in Seven Argentinian Cases with Spondylocarpotarsal Synostosis Syndrome

et al. 2022

View full text Add to dashboard Cite

Spondylocarpotarsal synostosis syndrome (SCT) is a very rare skeletal dysplasia characterized by vertebral, carpal, and tarsal fusion; growth retardation; and mild dysmorphic facial features. Variants in FLNB, MYH3, and RFLNA have been implicated in this dysplasia. We report the clinical and radiological follow-up of seven SCT pediatric cases associated with biallelic FLNB variants, from four Argentinian families. The seven cases share previously described facial characteristics: round facies, large eyes, and wide based nose; all of them had variable height deficit, in one case noted early in life. Other findings included clinodactyly, joint limitation without bone fusion, neurosensorial hearing loss, and ophthalmological compromise. All cases presented with spinal fusion with variable severity and location, carpal bones coalition, and also delay in carpal ossification. The heterozygous carrier parents had normal height values to −2.5 score standard deviation, without skeletal defects detected. Three different FLNB variants, one nonsense and two frameshift, were detected, all of which were predicted to result in a truncated protein or are degraded by nonsense mediated decay. All cases had at least one copy of the nonsense variant, c.1128C> G; p. (Tyr376*), suggesting the presence of a common ancestor.

show abstract

Spondylocarpotarsal synostosis syndrome. A rare case of short stature and congenital scoliosis

Cited by 3 publications

References 11 publications

Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report

Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report

Intervertebral disc degeneration is rescued by TGFβ/BMP signaling modulation in an ex vivo filamin B mouse model

Novel FLNB Variants in Seven Argentinian Cases with Spondylocarpotarsal Synostosis Syndrome

Contact Info

Product

Resources

About