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Cornelia de Lange syndrome

Cornelia de Lange Syndrome Research Fallback

⚠️ Fallback MONDO:0016033

Cornelia de Lange Syndrome Research Fallback

Deep-research provider attempts were made after the ORPHA:199 direct Orphanet/MONDO target was selected:

  • timeout 120 just research-disorder falcon Cornelia_de_Lange_Syndrome
  • timeout 120 just research-disorder openai Cornelia_de_Lange_Syndrome

Both commands printed the initial provider line, then stalled without producing a research output file and were terminated by the timeout. The curation therefore used the structured Orphanet cache plus fetched PubMed cache records as the auditable evidence base.

Literature Scope Checked

  • references_cache/ORPHA_199.md: direct Orphanet leaf record for Cornelia de Lange syndrome, including definition, autosomal dominant and X-linked inheritance, exact MONDO and OMIM mappings, prevalence, age of onset, disease-gene assertions, and HPO phenotype rows.
  • references_cache/PMID_29995837.md: international consensus statement supporting CdLS as a cohesin-complex gene disorder with intellectual disability, facial features, upper-limb anomalies, atypical growth, molecular diagnostics, and long-term management guidance.
  • references_cache/PMID_15146186.md: human NIPBL gene-discovery evidence, including sporadic and familial CdLS cases and multisystem clinical manifestations.
  • references_cache/PMID_15146185.md: NIPBL/delangin gene-discovery evidence connecting Scc2/Nipped-B homolog function to CdLS and limb-patterning defects.
  • references_cache/PMID_23505322.md: human CdLS cohort evidence supporting frequent NIPBL somatic mosaicism and buccal swab DNA testing when blood testing is negative.
  • references_cache/PMID_26701315.md: human NIPBL series supporting de novo heterozygous NIPBL variants, germline and somatic NIPBL mutations, and first-line buccal cell DNA analysis for diagnostic sensitivity.
  • references_cache/PMID_19468298.md: human CdLS cell-line evidence for transcriptional dysregulation, cohesin regulatory-region binding, and phenotype-severity correlation.
  • references_cache/PMID_26581180.md: SMC1A-mutant CdLS cell evidence that mutant cohesin affects RNA polymerase II regulation.
  • references_cache/PMID_19763162.md: Nipbl heterozygous mouse-model evidence for multisystem defects and transcriptional dysregulation consistent with CdLS.
  • references_cache/PMID_25921057.md: clinical management paper used only for the Bohring-Opitz syndrome differential diagnosis.

Curation Conclusions

  • Disease identity is the syndrome-level disorder ORPHA:199, exact to MONDO:0016033 and OMIM:122470.
  • The core disease mechanism is pathogenic variation in cohesin structural or regulatory genes, especially NIPBL, causing impaired cohesin loading, altered chromatin/regulatory-region binding, and developmental transcriptional dysregulation.
  • Orphanet directly supports the curated phenotype profile, including synophrys, thick eyebrows, highly arched eyebrows, brachycephaly, microcephaly, micrognathia, high palate, long philtrum, downturned corners of mouth, short nose, depressed nasal bridge, anteverted nares, short neck, delayed eruption of teeth, generalized hirsutism, intellectual disability, hypertonia, anxiety, compulsive behaviors, attention deficit hyperactivity disorder, sleep abnormality, intrauterine growth retardation, short stature, delayed skeletal maturation, micromelia, small hand, toe syndactyly, short foot, oligodactyly, feeding difficulties, gastroesophageal reflux, hearing impairment, atresia of the external auditory canal, and ventricular septal defect.
  • Evidence-backed management is supportive and multidisciplinary, with genetic counseling and molecular testing supported by the consensus statement, inheritance evidence, and buccal swab testing evidence for mosaic cases.