Jackson-Weiss Syndrome

Last update 08 May 2025

Basic Info

Synonyms

Acrocephalosyndactyly Jackson Weiss type, CRANIOSYNOSTOSIS, MIDFACIAL HYPOPLASIA, AND FOOT ABNORMALITIES, Craniosynostosis, midfacial hypoplasia, and foot abnormalities

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Introduction

A rare, autosomal dominant inherited disorder caused by mutations in the FGFR2 gene. It is characterized by the premature fusion of the bones of the skull (craniosynostosis) and foot abnormalities. The craniosynostosis results in a malformed skull, widely spaced eyes, and a bulging forehead. The foot abnormalities consist of short and wide first toes, which bend away from the other toes. In addition, syndactyly in some toes may be present. The hands are almost always normal.

100 Clinical Results associated with Jackson-Weiss Syndrome

100 Translational Medicine associated with Jackson-Weiss Syndrome

0 Patents (Medical) associated with Jackson-Weiss Syndrome

Literatures (Medical) associated with Jackson-Weiss Syndrome

01 Jan 2025·Journal of Clinical Orthopaedics and Trauma

Clinical and radiological insights into fibrodysplasia ossificans progressiva: A report on two cases

Article

Author: Rapole, Sanika ; Mehta, Bhavika ; Sodhai, Vivek

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic illness marked by progressive heterotopic ossification of tendons, ligaments, fascia, and skeletal muscle, leading to immobility and reduced quality of life. Early recognition is critical to avoiding flare-ups often triggered by trivial trauma or medical interventions. This report presents two early-diagnosed FOP cases-one at 6 months, the other at 18 months-both with typical features and congenital great toe abnormalities. Early detection enables preventive strategies that enhance the quality and longevity of affected children's lives. Increased awareness among healthcare professionals about the unique presentation of FOP is vital for prompt diagnosis.

19 Jun 2023·Philosophical transactions of the Royal Society of London. Series B, Biological sciences

Functional identification of hot-spot mutations in cardiac calcium channel genes associated with the J wave syndromes.

Article

Author: Zhang, Xiang ; Antzelevitch, Charles ; Zeng, Bin ; Glikson, Michael ; Powers, Andrew ; Hu, Dan ; Schimpf, Rainer ; Barajas-Martinez, Hector

J wave syndrome (JWS) is an inherited cardiac channelopathy associated with malignant ventricular arrhythmias and sudden cardiac death (SCD), which comprises early repolarization syndrome and Brugada syndrome. Here, we explore the association between variants in the L-type calcium channel gene subunits, α_1C (CACNA1C) and β2b (CACNB2b), and the JWS phenotype. Using next-generation genetic sequencing of 402 JWS probands and their family members, we identified a CACNA1C-G37R (p.Gly37Arg) mutation in five individuals in four families, two of which had a family history of SCD as well as a CACNB2b-S143F (p.Ser143Phe) mutation in seven individuals in three families, two of which had a family history of SCD. The variants were located in exon 2 in CACNA1C and exon 5 in CACNB2b; both were in highly conserved amino acid residues. Whole-cell patch-clamp results showed that compared with the wild-type group, calcium current density of CACNB2b-S143F and CACNA1C-G37R were significantly lower displaying a dominant-negative effect. Our findings provide further support for the hypothesis that variants in CACNA1C and CACNB2b are associated with JWS. The results suggest that mutations in these two genes lead to loss-of-function of the cardiac calcium channel current warranting their inclusion in genetic screening protocols. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

01 Oct 2022·Circulation: Genomic and Precision Medicine

Acacetin, a Potent Transient Outward Current Blocker, May Be a Novel Therapeutic for KCND3 -Encoded Kv4.3 Gain-of-Function-Associated J-Wave Syndromes

Article

Author: Kim, C.S. John ; Ye, Dan ; Antzelevitch, Charles ; Giudicessi, John R. ; Ackerman, Michael J. ; Tester, David J. ; Zhou, Wei ; Hu, Dan ; Hamrick, Samantha K. ; Barajas-Martinez, Hector

Background: The transient outward current (Ito) that mediates early (phase 1) repolarization is conducted by the KCND3 -encoded Kv4.3 pore-forming α-subunit. KCND3 gain-of-function mutations have been reported previously as a pathogenic substrate for J wave syndromes (JWS), including the Brugada syndrome and early repolarization syndrome, as well as autopsy-negative sudden unexplained death (SUD). Acacetin, a natural flavone, is a potent Ito current blocker. Acacetin may be a novel therapeutic for KCND3 -mediated J wave syndrome. Methods: KCND3-V392I was identified in an 18-year-old male with J wave syndrome/early repolarization syndrome, and a history of cardiac arrest including ventricular tachycardia/ventricular fibrillation and atrial fibrillation/atrial flutter. Pathogenic KCND3 mutation was engineered by site-directed mutagenesis and co-expressed with wild-type KChIP2 in TSA201 cells. Gene-edited/variant-corrected isogenic control and patient-specific pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) from the p. Val392Ile-KCND3-positive patient were generated. I to currents and action potentials were recorded before and after treatment with Acacetin using the whole cell patch-clamp and multielectrode array technique. Western blot and immunocytochemistry were performed to investigate KCND3 expression. Results: KCND3-V392I demonstrated a marked gain-of-function phenotype, increasing peak I to current density by 92.2% ( P <0.05 versus KCND3-WT). KCND3 expression was significantly increased in KCND3-V392I-derived iPSC-CMs ( P <0.05 versus isogenic control). While KCND3-WT revealed an IC50 of 7.2±1.0 µmol/L for acacetin effect, 30 µmol/L acacetin dramatically inhibited KCND3-V392I peak Ito current density by 96.2% ( P <0.05 versus before Acacetin). Ito was also increased by 60.9% in Kv4.3-V392I iPSC-CM ( P <0.05 versus isogenic control iPSC-CM). Ten micromoles per liter acacetin, a concentration approaching its IC50 value, inhibited Ito by ≈50% in patient-derived iPSC-CMs and reduced the accentuated action potential notch displayed in KCND3-V392I-derived iPSC-CMs. Conclusions: This preclinical study provides pharmacological and functional evidence to suggest that Acacetin may be a novel therapeutic for patients with KCND3 gain-of-function-associated J wave syndrome by inhibiting I to and abolishing the accentuated action potential notch in patient-derived iPSC-CMs.

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Jackson-Weiss Syndrome

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