International Expert Opinion on Standard of Care for Patients With Schinzel-Giedion Syndrome: A Modified Delphi Study

Am J Med Genet A. 2025 Jun;197(6):e64015. doi: 10.1002/ajmg.a.64015. Epub 2025 Feb 19.

Abstract

Schinzel-Giedion Syndrome (SGS) is an ultra-rare, multisystem, genetic developmental disorder caused by gain-of-function pathogenic variants in the SETBP1 gene. No standard of care (SoC) recommendations currently exist. To assess expert opinion on SoC for individuals with SGS using a modified Delphi method. A multidisciplinary panel of 21 experts from the USA and Europe was assembled. Experts responded to a two-round questionnaire, with a subgroup participating in a virtual workshop, through which recommendations pertaining to the diagnosis, monitoring, treatment, and management of SGS were iteratively developed. Consensus was defined as ≥ 70% of respondents demonstrating agreement/disagreement with 6-point Likert scale questions, or ≥ 70% of respondents selecting a given multiple-choice question option. Overall, 81/94 statements achieved consensus. Experts agreed that the recommendations should be considered applicable to any individual with confirmed SGS or an indicative phenotype and any SETBP1 gain-of-function mutation. Key considerations included early and sustained involvement of a multidisciplinary team, routine monitoring for common tumors, neurologic, renal, genitourinary, pulmonary, musculoskeletal and gastrointestinal manifestations/complications, and facilitation of shared decision-making processes. These recommendations should help guide clinicians and families/caregivers in care decisions to enhance quality and duration of life for individuals with SGS and facilitate shared decision-making.

Keywords: Delphi technique; Schinzel‐Giedion syndrome; recommendations; standard of care.

MeSH terms

  • Abnormalities, Multiple* / diagnosis
  • Abnormalities, Multiple* / epidemiology
  • Abnormalities, Multiple* / genetics
  • Abnormalities, Multiple* / pathology
  • Abnormalities, Multiple* / therapy
  • Autistic Disorder* / diagnosis
  • Autistic Disorder* / genetics
  • Autistic Disorder* / therapy
  • Carrier Proteins
  • Consensus
  • Craniofacial Abnormalities* / diagnosis
  • Craniofacial Abnormalities* / epidemiology
  • Craniofacial Abnormalities* / genetics
  • Craniofacial Abnormalities* / pathology
  • Craniofacial Abnormalities* / therapy
  • Delphi Technique
  • Hand Deformities, Congenital* / diagnosis
  • Hand Deformities, Congenital* / epidemiology
  • Hand Deformities, Congenital* / genetics
  • Hand Deformities, Congenital* / pathology
  • Hand Deformities, Congenital* / therapy
  • Humans
  • Intellectual Disability* / diagnosis
  • Intellectual Disability* / epidemiology
  • Intellectual Disability* / genetics
  • Intellectual Disability* / pathology
  • Intellectual Disability* / therapy
  • Limb Deformities, Congenital* / diagnosis
  • Limb Deformities, Congenital* / epidemiology
  • Limb Deformities, Congenital* / genetics
  • Limb Deformities, Congenital* / pathology
  • Limb Deformities, Congenital* / therapy
  • Mutation
  • Nails, Malformed* / diagnosis
  • Nails, Malformed* / epidemiology
  • Nails, Malformed* / genetics
  • Nails, Malformed* / pathology
  • Nails, Malformed* / therapy
  • Nuclear Proteins
  • Standard of Care*

Substances

  • SETBP1 protein, human
  • Carrier Proteins
  • Nuclear Proteins

Supplementary concepts

  • Schinzel-Giedion syndrome