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Neuroendocrinology and Pituitary

SUN-037 - Endocrine Manifestations of Luscan-Lumish Syndrome Due to A Novel SETD2 Frameshift Mutation

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor

    Abstract Poster Presenter(s)

  • Julia May Huang, MD

    PGY-2 Resident
    Julia Huang
    Los Angeles, CA, United States

    • Co-Author(s)

  • DA

    Diana Ashouri, MD

    Pasadena, CA, United States

    • Senior Author/Primary Investigator(s)

  • AD

    Alyssa L. Dominguez, MD

    Assistant Professor of Clinical Medicine
    KECK SCHOOL OF MEDICINE OF USC
    Los Angeles, United States

Disclosure(s):
Julia May Huang, MD: No financial relationships to disclose
Background
Luscan-Lumish syndrome (LLS) is a rare autosomal dominant disorder caused by pathogenic variants in the SETD2 gene, characterized by postnatal overgrowth, obesity, developmental delay, seizures, and Chiari I malformation. Detailed endocrine characterization of this syndrome remains limited in the literature.

Case Presentation
We report a 47-year-old woman with a novel frameshift mutation in SETD2 (c.4451_4454del, p.Lys1486Argfs*28), presenting with severe obesity (BMI 62.9 kg/m²), hyperprolactinemia, hypogonadotropic hypogonadism, hirsutism, seizures, and Chiari I malformation. The patient experienced rapid weight gain of approximately 200 pounds beginning at age 14-15 despite reportedly normal eating habits, accompanied by severe hirsutism and secondary amenorrhea. Laboratory evaluation revealed inappropriately low gonadotropins (LH 0.3 IU/L, FSH 0.5 IU/L) with low estradiol (26.4-48 pg/mL), hyperprolactinemia (140-150 ng/mL), and prediabetes (HbA1c 5.7%). Despite evaluation at multiple institutions over three decades, including the National Institutes of Health, no unifying diagnosis was established until genetic testing revealed a pathogenic SETD2 variant.

Conclusion
This case expands the phenotypic spectrum of Luscan-Lumish syndrome to include characterization of hypogonadotropic hypogonadism, hyperprolactinemia, and metabolic dysfunction. To our knowledge, this represents the first comprehensive report of the endocrine manifestations of LLS, thereby extending the recognized clinical features of this rare syndrome. This case underscores the importance of considering genetic testing in adolescents and adults with rapid-onset severe obesity accompanied by multisystem neurodevelopmental features, brain malformations, or atypical endocrine presentations. Early genetic diagnosis enables appropriate multidisciplinary care, genetic counseling, and potential access to emerging targeted therapies for genetic obesity syndromes.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*