BCARD syndrome is a rare autosomal recessive connective tissue disorder characterized by bone abnormalities, cataract, risk of arterial rupture due to vascular aneurisms or dissections, and sensorineural deafness. BCARD, linked to biallelic pathogenic variants in the PLOD3 gene, was characterized in 10 cases across six reports. Here we present an 11-year-old female patient whose phenotype, alongside the clinical features specific to BCARD syndrome, also exhibited vesico-ureteral reflux, intestinal anomaly, minor cardiac anomalies, focal epilepsy, and brain abnormalities, including polymicrogyria and heterotopia. Whole-exome sequencing revealed two novel nucleotide variants (c.335A>G and c.2158G>T) in the PLOD3 gene. The first variant functions as a cryptic splice site variant, and RNA analysis confirmed that it causes a 4 bp truncation of exon 3. This truncation induces a frameshift, resulting in the formation of a premature termination codon (p.(Asp112AlafsTer4)). The second variant, a nonsense mutation located in the final exon, leads to the truncation of a functionally critical protein domain. This case expands our understanding of BCARD syndrome variability, aiding in earlier detection of skeletal pathology, brain, ocular, vascular complications, and intestinal, ureteral, cardiac abnormalities. SMARCA2-related Nicolaides-Baraitser syndrome (SMARCA2-NCBRS) is characterized by commonly shared dysmorphic features including sparse scalp hair, prominence of the interphalangeal joints and distal phalanges due to decreased subcutaneous fat, characteristic coarse facial features, microcephaly (typically acquired), seizures, and developmental delay / intellectual disability. Developmental delay / intellectual disability is severe in nearly half of affected individuals, moderate in one third, and mild in the remainder. Nearly one third never develop speech or language skills. Seizures are of various types and can be difficult to manage, requiring multiple anti-seizure medications to achieve reasonable control. Regression or lack of developmental progress has been noted with the onset of seizures in some affected individuals. Behavioral issues can include autistic-like features (perseveration, hyperacusis), with a minority of affected individuals being diagnosed clinically with an autism spectrum disorder. Cryptorchidism is common in males. About half of affected individuals have growth deficiency and short stature. Delayed tooth eruption with hypo- or oligodontia has also been reported. Radiographic findings may include cone-shaped epiphyses, metaphyseal flaring of the phalanges, and shortening of the phalanges, metacarpals, and/or metatarsals (especially of the 4th and 5th rays) of the hands; platyspondyly; flat intervertebral disc space; and pelvic/femoral anomalies. Rare findings include conductive hearing loss, refractive error / astigmatism, and congenital heart defects. The diagnosis of SMARCA2-NCBRS is established in a proband with suggestive findings and a heterozygous SMARCA2 pathogenic variant identified by molecular genetic testing. Treatment of manifestations: Standard therapy for developmental delay / intellectual disability, behavioral issues, epilepsy, poor growth, myopia, astigmatism, hearing loss, dental issues, cryptorchidism, and congenital heart defects. Surveillance: At each visit, measure growth parameters; evaluate nutritional status and safety of oral intake; monitor those with seizures; assess for new manifestations; monitor developmental progress and educational needs; assess for behavioral issues such as short attention span, sensitivity to loud noises, and oral sensitivity; and evaluate mobility and self-help skills. Dental evaluation at least every six months after the eruption of first dentition. Annual audiology evaluation in childhood. Ophthalmology evaluation per treating ophthalmologist. SMARCA2-NCBRS is expressed in an autosomal dominant manner and typically caused by a de novo SMARCA2 pathogenic variant; the risk to other family members is presumed to be low. Once a SMARCA2 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Stickler syndrome is a collagen disorder associated with hypermobility and juvenile osteoarthritis in multiple joints. This report presents a 12-year-old adolescent boy with Stickler syndrome presenting with bilateral ankle pain. He had bilateral distal tibial recurvatum-valgus deformity and distal tibial slipped epiphysis (DTSE). He underwent osteotomy along the true plane of deformity and internal fixation. At the latest follow-up, he had decreased pain and improved clinical and radiographic alignment. DTSE is a rare condition contributing to ankle deformity. Previously reported in renal osteodystrophy and myelomeningocele, DTSE is reported herein for the first time in association with Stickler syndrome.

Skeletal dysplasias (SD) are rare genetic disorders affecting skeletal development and bone growth. Whereas specific gene mutations have been identified in many, however, the molecular signaling pathways contributing to the phenotype are poorly understood. The C-type natriuretic peptide (CNP) signaling pathway is a driver of normal endochondral bone growth and underlies the impact of several genetic disorders of bone growth, including achondroplasia, the most common form of SD. In this cross-sectional study of 73 children with SD, comprising 7 distinct forms, we have examined the association of plasma concentrations of bioactive CNP and bio-inactive NTproCNP (recognized bio markers driving growth) and of collagen X marker (CXM) (an established biomarker of the growth plate response) with age and with annualized height velocity (HV). Although significant associations were identified with age in several disorders, the association of NTproCNP and of CXM with HV was aberrant except in type II collagen disorders and MOPD II. In OI, CNP and NTproCNP were reduced in proportion to severity of OI phenotype. Reduction in CNP exceeded NTproCNP, suggesting that higher rate of clearance/degradation of bioactive CNP occurs in OI. Across a wide range of HV in subjects with OI, biomarkers were dissociated and unrelated to HV. Similar changes were observed in 3 other forms of SD (multiple epiphyseal dysplasia, microcephalic osteodysplastic primordial dwarfism type II, and Morquio A syndrome). Although limited numbers of affected individuals within each group were studied employing a single sample at one time point, the results indicate aberrant responses both within biomarkers and when related to HV. Importantly, we identify enhanced rates of CNP clearance in OI and other forms of SD, which suggests CNP agonists could have therapeutic benefits. Skeletal dysplasias (SD) are rare genetic disorders affecting bone development and growth. C-type natriuretic peptide (CNP) and collagen X marker (CXM) are proteins involved in bone growth and are impacted in SD. In this study of 73 children with SD, we have looked at these protein levels compared with age and height velocity (HV). In some of these conditions, there was an association between these levels and age. However, in all but 2 of these conditions, there was no association between these levels and HV, which is a change from the general population and indicates growth plate differences in this population.

Wolcott-Rallison syndrome (WRS) is an autosomal recessive multisystemic genetic disorder caused by homozygous mutation in the eukaryotic translation initiation factor 2 alpha kinase 3 gene. It typically presents with neonatal onset insulin-dependent diabetes. Here, we report a 14-year-old male patient with WRS who presented with late-onset diabetes mellitus. A 14-year-old male patient presented with acute liver failure secondary to acute gastroenteritis. On physical examination, signs of chronic malnutrition and muscle atrophy in the extremities were evident, accompanied by a waddling gait. Infectious, autoimmune, and metabolic diseases were excluded. Liver tests improved within 3 weeks with supportive treatment. Direct radiographs were consistent with multiple epiphyseal dysplasia. High blood glucose levels were observed at follow-up in the intensive care unit. At the 4-month follow-up, HbA1c increased to 55 mmol/mol (7.2 %) and basal insulin treatment was started at a dose of 0.4U/kg/day. Glycemic control was achieved after 6 months. Diabetes typically manifests within the first 6 months of life, with a median age of 2.5 months, and has been observed in all patients with WRS reported in the literature. Our case is an interesting WRS patient whose diabetes started at the age of 14 years with a novel mutation.

Acetabular subchondral cysts are commonly identified signs of joint degeneration and arthritis. This pathology is generally considered a relative contraindication for hip preservation surgery. To investigate the effect of arthroscopic bone grafting for the treatment of acetabular subchondral cysts. Cohort study (diagnosis); Level of evidence, 3. We completed a retrospective analysis of hip arthroscopies performed by the senior author between 2013 and 2021. Patients with radiologic evidence of acetabular cysts who underwent arthroscopic bone grafting, with or without subsequent periacetabular osteotomy (PAO) and/or derotational femoral osteotomy with a minimum of 2-year follow-up, were included in the analysis. Patients undergoing surgical treatment for diagnoses of slipped capital femoral epiphysis, Legg-Calves-Perthe disease, osteochondromatosis, or postdislocation syndrome, as well as patients who refused to participate in the study, were excluded. We compared the patient-reported outcomes (PROs) for patients who underwent arthroscopic bone grafting with a case-matched control group without acetabular cysts with the same surgical route (hip arthroscopy or hip arthroscopy followed by PAO). An "inside-out" arthroscopic bone grafting technique was utilized, which allowed for precise access to the cystic cavity through the articular side. We analyzed postoperative PROs at a minimum of 2 years postoperatively using the international Hip Outcome Tool (iHOT-12) and Nonarthritic Hip Score (NAHS). In total, there were 44 hips in the experimental group and 78 hips in the control group. The mean PRO interval in the experimental group was 3.4 years (range, 2-5 years postoperatively), with 20 patients reaching PROs 5 years postoperatively. The experimental group reported significant improvement of iHOT-12 and NAHS scores postoperatively (both P < .001). Postoperative iHOT-12 and NAHS scores did not significantly differ between groups over a 5-year follow-up interval (P = .26 and .17, respectively). Radiographic evidence of cyst healing was achieved in all 7 patients who underwent postoperative magnetic resonance imaging, with 3 cases of complete resolution. Acetabular subchondral cysts treated with an inside-out method of arthroscopic bone grafting in the setting of hip preservation surgery with or without PAO was associated with a significant improvement in midterm PROs, comparable with a control group of patients without acetabular cysts who did not undergo bone grafting. Our results support the use of arthroscopic grafting in appropriately selected patients and suggest that hip preservation is not contraindicated in patients with acetabular subchondral cysts.