P461: Cartilage-hair hypoplasia: Expanding the association of severe prenatal skeletal findings

Treatment and Management: During the proband's diagnostic odyssey, she was admitted to the Vanderbilt ICU for acute hypoxic respiratory failure secondary to obesity at age 8 years.Inpatient care was thus transferred to the Vanderbilt Medical Weight Loss Center to ameliorate airway compromise through weight loss.Preadmission medications including insulin glargine 38 u nightly, gabapentin 100 mg thrice daily, and levetiracetam 5 mL twice daily were noted to further contribute to the patient's obesity.A diet centered around ultra-processed carbohydrates, a dearth of physical exercise due to musculoskeletal constraint, food preoccupation, and hyperphagia were also noted.Known monogenic causes of obesity, including Prader-Wili Syndrome and Bardet-Biedl Syndrome, were excluded given the proband's extant GS and methylation data.Semaglutide 0.25 mg weekly and preprandial pramlintide were started off-label.Outcome and Follow-Up: The proband's management at Vanderbilt University Medical Center also demonstrated a weight loss treatment effect from semaglutide and pramlitinide at age eight years, younger than validated in extant literature.Discussion: Ferraz et al expanded upon MED12L's association with variants in chromosomal structure.We found diploid-triploid mosaicism in our case, supporting the hypothesis that loss of MED12L function may induce chromosomal instability.Our report expands the corpus of Nizon-Isidor Syndrome in literature and supports the hypothesis that heterozygous loss of MED12L function may induce chromosomal instability during embryonic development.Conclusion: Our proband's case suggests future research directions for the treatment of pediatric obesity secondary to mosaicism.Effective collaboration between clinical specialties, medical professions, and foundational scientists is requisite for diagnosis, clinical management, and knowledge generation in conditions like this.Multidisciplinary clinical and research programs, such as the UDN, are helpful in navigating some of the barriers to diagnosis and further knowledge of rare disease.Introduction: Nizon-Isidor Syndrome is a rare disease caused by heterozygous variants in MED12L, with few cases reported in literature.Case Presentation: We describe the case of a seven-year-old female referred to the Undiagnosed Diseases Network (UDN) at Vanderbilt University Medical Center (VUMC) for developmental delay, hemi-hypertrophy of the right leg, laryngeal cleft, esotropia, abnormal skin pigmentation, sectoral iris hypopigmentation, dysphagia, periventricular nodular heterotopia, seizure disorder, morbid obesity, and a pelvic kidney.