Schwartz-Jampel syndrome (SJS) type 1 (OMIM; #255800), a rare cause of skeletal dysplasia, is characterized by myotonic myopathy, chondrodystrophy, short stature, facial and eye abnormalities. SJS type 1 develops due to variations in the HSPG2 gene which produces the “perlecan” molecule, one of the main proteoglycans of the basement membrane. A 6-year-old girl presented with short stature, a mask face, shrunken lips, narrow palpebral opening due to blepharospasm, stiffness of facial muscles, micrognathia, overlapping teeth, a short neck, and a bell-shaped thorax due to myotonic myopathy. She was diagnosed with SJS type 1 due to compound heterozygosity of two novel variations in the HSPG2 gene. In patients with short stature and an accompanying myotonic myopathy SJS should be considered. Compound heterozygosity may cause typical clinical findings of SJS. In case of suspicion creatinine kinase levels can be measured, and the determination of myotonia may require evaluation with electromyography. Once the diagnosis is made, patients should be carefully monitored in terms of growth, neuromuscular disorders, joints problems and bone health.

BackgroundBlepharospasm is one of the most limiting symptoms in patients with Schwartz-Jampel syndrome and can affect early visual development, causing amblyopia and leading to disability. There is no consensus on the optimal management of blepharospasm in these patients. This systematic review aims to evaluate the current evidence for the appropriate management strategies for blepharospasm in Schwartz-Jampel syndrome.MethodsThis was a prospective register of systematic reviews (PROSPERO)-registered (CRD42024569495), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline-adherent systematic review. Databases searched include Medline (PubMed), Scopus, and Web of Science from any time to February 1st, 2025. All scientific manuscripts published discussing the management of blepharospasm in patients with Schwartz-Jampel syndrome were included. A novel therapeutic algorithm has been developed and proposed.ResultsFrom an initial number of 59 articles, 15 of them were included. No clinical trials nor observational studies were found. All these 15 articles were case series or case reports (quality of evidence: 4 or 5), involving 21 patients. A great heterogeneity in how to manage blepharospasm in Schwartz-Jampel syndrome was gathered. Therapeutic options included oral drugs (sodium channel blockers: carbamazepine, phenytoin, and procainamide), botulinum-toxin-A, and eyelid surgery (orbicularis myectomy). The management algorithm proposal is oral sodium channel blockers as the first option and eyelid surgery as the second option treatment. Botulinum-toxin-A might be considered a therapeutic step prior to surgery.ConclusionsThe published evidence regarding management strategies for blepharospasm in Schwartz-Jampel syndrome is scarce and of low quality. Since this nosology is a very rare disease, efforts should be promoted to conduct clinical research and a consensus document for the management of blepharospasm.

Perlecan is an essential multi-domain, disulfide bond rich basement membrane protein. Mutations in perlecan cause Schwartz-Jampel syndrome and dyssegmental dysplasia. While there has been a large body of experimental work reported on perlecan, there is only minimal structural information available to date. There is no prior structural data for region 3 of perlecan in which some Schwartz-Jampel syndrome causing point mutations have been reported. Here, we produce constructs of the disulfide rich region 3 of perlecan along with five mutations previously reported to cause Schwatz-Jampel syndrome. Four of the mutations resulted in decreased yields and thermal stability compared to the wild-type protein. In contrast, the P1019L mutation was produced in good yields and showed higher thermal stability than the wild-type protein. The crystal structures for both the wild-type and P1019L mutation were solved. As expected, both showed laminin IV-like and laminin-type EGF-like domains, with the P1019L mutation resulting in only a minor conformational change in a loop region and no significant changes in regular secondary or tertiary structure.

Stüve-Wiedemann syndrome (SWS) is a rare autosomal recessive disorder that is characterized by bowing of long bones, dysautonomia, temperature dysregulation, swallowing and feeding difficulties, and frequent respiratory infections. Respiratory distress and hyperthermic events are the leading causes of early neonatal death, and most patients are not expected to survive past infancy. Here, we report on the survival of a 5-year-old male with SWS, discussing his case presentation, providing a brief clinical course, and discussing the outcome. This case adds to the literature surrounding rare instances of childhood survivors of SWS and raises awareness for this syndrome to facilitate an earlier recognition, intervention, and genetic counseling for the families, thereby improving understanding of this disease and the health outcomes for the children affected by this condition.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive disorder characterized by muscle stiffness (myotonia) and chondrodysplasia. This disease is caused by biallelic loss of function mutations in the HSPG2 gene, which encodes the core protein of perlecan. This study aims to investigate causative variants in two sisters born to consanguineous Iranian parents. Both patients were presented with myotonia and a mask-like face; moreover, they showed a less common symptom, gastrointestinal bleeding, which is not typical of SJS and has only been reported in one patient. Regarding the crucial role of perlecan in vascular structure and mucosal stability, bleeding disorders could be expected in perlecan dysfunctions. In addition to the case study, a comprehensive literature review was conducted to gather information on similar genetic variants, associated clinical features, and possible disease mechanisms. Results of this study contribute to our understanding of the genetic and clinical aspects of Schwartz-Jampel syndrome, and more importantly, the manifestation of gastrointestinal bleeding in patients with Schwartz-Jampel syndrome.