Escobar syndrome (ES) is a rare, nonlethal form of multiple pterygium syndrome, primarily characterized by joint contractures, pterygium formation, craniofacial anomalies, and scoliosis. Although scoliosis is frequently reported in ES, there is limited literature describing the broader spectrum of clinical comorbidities and intraspinal abnormalities. This study presents the largest reported cohort of ES patients to date, aiming to characterize their orthopaedic manifestations, scoliosis prevalence, and neurological anomalies. A retrospective review was conducted at a single pediatric institution from 2000 to 2024. Patients with a confirmed diagnosis of ES and scoliosis were included, with a minimum of 2 years of follow-up. Data collected included demographics, clinical comorbidities (pulmonary, cardiac, craniofacial), radiographic findings, spinal deformities, intraspinal anomalies on MRI, surgical interventions, and complications. Twenty patients met the inclusion criteria. Craniofacial anomalies were present in 100% of patients, while pulmonary disorders (43%) and cardiac anomalies (23%) were also common. Intraspinal anomalies were identified in 50% of patients, including a tethered spinal cord in 40%. Fourteen patients (70%) underwent spinal surgery at a mean age of 7 years (range, 1 to 14) with a mean follow-up of 7 years (range, 2 to 14). In all, 14 patients had spinal surgery, including 10 patients with growth-friendly procedures and 4 patients with an instrumented posterior spinal fusion (iPSF). The mean major curve improved from 77 degrees (range, 16 to 113) at initial presentation to 51 degrees (range, 18 to 110) at final follow-up. VEPTR was associated with the highest complication rate (7/3 patients, 233%), followed by MCGR (2/6 patients, 33%) and PSF (1/4 patients, 25%). Scoliosis is a common and often severe orthopaedic manifestation in patients with Escobar syndrome, frequently accompanied by a variety of comorbidities and intraspinal anomalies such as a tethered spinal cord. Surgical correction using growth-friendly techniques can be effective, but complication rates with VEPTR remain high. These findings highlight the importance of thorough preoperative imaging and thoughtful surgical planning. Level IV, therapeutic/prognostic studies.

Contractures, pterygia, and spondylocarpotarsal fusion syndrome (CPSFS) comprises a group of extremely rare genetic disorders characterized by congenital craniofacial and musculoskeletal abnormalities. With fewer than 500 cases reported globally, this scarcity contributes to limited clinical recognition, frequent diagnostic delays or errors, and missed opportunities for timely intervention. We present this case to enhance awareness of CPSFS and report a novel pathogenic variant in MYH3 (previously undocumented in the literature) that broadens the known mutational spectrum of MYH3 and enriches the phenotypic profile of CPSFS. A female neonate was born at 29 weeks, prenatal ultrasound and magnetic resonance imaging revealed scoliosis and vertebral fusion. The postnatal examination showed microstomia, low-set ears, a short neck with webbing, and flexion contractures at shoulders, elbows, knees, and hands. The whole genome sequencing found novel variants, namely NM_002470.4: c.1914del C; p. Lys639Argfs*18 and NM_002470.4: c.-68 + 4A > T, in the MYH3. CPSFS 1. Immediately after birth, noninvasive ventilatory support was initiated. The surgical team conducted comprehensive evaluations, while concurrent genetic testing was performed. Given the infant's multiple systemic skeletal malformations and inability to sustain spontaneous respiration, surgical intervention was deemed nonviable. Due to severe thoracic deformity and bronchopulmonary dysplasia, the infant required continuous noninvasive ventilation from birth and remained ventilator-dependent. At a corrected gestational age of 36 weeks and 4 days, life-sustaining therapy was withdrawn following thorough counseling and parental deliberation. The infant died shortly thereafter. Prenatal ultrasound and fetal magnetic resonance imaging can reliably detect characteristic manifestations including scoliosis, joint developmental abnormalities, and clubfoot. Thus, regular prenatal surveillance plays a critical role in early disease identification. For suspected cases, genetic counseling and diagnostic testing enable informed parental decision-making regarding management of affected offspring and future reproductive planning.

Fetal akinesia is a broad term used to describe absent (or reduced, fetal hypokinesia) fetal movements, and it can be detected as early as the first trimester. Depending on the developmental age of onset, anything that interferes or limits the normal in utero movement results in a range of deformations affecting multiple organs and organ systems. Arthrogryposis, also termed arthrogryposis multiplex congenita (AMC), is a definitive terminology for multiple congenital contractures, with two major subgroups; amyoplasia and distal arthrogryposis (DA). The spectrum includes fetal akinesia deformation sequence (FADS), lethal congenital contracture syndrome (LCCS), and multiple pterygium syndrome (MPS). Variants in more than >400 genes are known to cause AMC, and it is increasingly recognized that variants in genes encoding critical components (including ventral horn cell, peripheral nerve, neuromuscular junction, skeletal muscle) of the extended motor unit underlie ∼40% of presentations. With unbiased screening approaches, including sequencing of comprehensive disease gene panels, exomes and genomes, novel genes and phenotypic expansions associated with known human disease genes have been uncovered in the setting of fetal akinesia. Autosomal-recessive titinopathy is the most frequent genetic cause of AMC. Accurate genetic diagnosis is critical to genetic counseling and informing family planning. Around 50% remain undiagnosed following comprehensive prenatal, diagnostic or research screening. Comprehensive phenotyping and periodic reanalysis with appropriate genomic tools are valuable strategies when faced with initial inconclusive results. There are likely many novel causative genes still to identify, which will inform our understanding of the molecular pathways underlying early human development and in utero movement.

Bruck syndrome is a rare, autosomal-recessive condition associated with features of both arthrogryposis and osteogenesis imperfecta. It is characterised by congenital large joint contractures with pterygia and bone fragility, leading to fractures and deformities, along with a short stature caused by progressive skeletal deformities. There are fewer than 50 described cases of Bruck syndrome in the literature, with no reported cases in pregnancy. We describe a case of a successful pregnancy in a woman with Bruck syndrome.In pregnant women with Bruck syndrome, we recommend a multidisciplinary approach including input from obstetric and fetal medicine specialists, midwives, anaesthetists, geneticists, occupational therapists and physiotherapists.

Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3.