Abstract
RATIONALE: 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. PATIENT CONCERNS: 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. DIAGNOSES: CPSFS 1. INTERVENTIONS: 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. OUTCOMES: 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 At a corrected gestational age of 36 weeks and 4 days, life-sustaining therapy was withdrawn following thorough counseling and parental deliberation.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. LESSONS: 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.