Distinct Clinical Presentations of Menke-Hennekam Syndrome: Insights From CREBBP and EP300 Variants

KETENCİ İŞLEK S., ÜREL DEMİR G., ÜTİNE G. E., ŞİMŞEK KİPER P. Ö.

Journal of Child Neurology, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1177/08830738261474118
  • Dergi Adı: Journal of Child Neurology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, BIOSIS, EBSCO Education Source, EMBASE, MEDLINE, MLA - Modern Language Association Database, Psycinfo, MLA International Bibliography, Academic Search Ultimate (EBSCO), Social Science Premium Collection (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Education Collection (ProQuest), Education Source Ultimate (EBSCO), Health Research Premium Collection (ProQuest)
  • Anahtar Kelimeler: developmental delay, genetics, intellectual disability, neurodevelopment, next-generation sequencing
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Menke-Hennekam syndrome types 1 and 2 (MKHK1 and MKHK2) are autosomal dominant neurodevelopmental disorders characterized by psychomotor developmental delay, intellectual disability, and dysmorphic features. MKHK1 is caused by heterozygous variants in exons 30-31 of the CREBBP gene, whereas MKHK2 results from heterozygous variants in EP300. Although these genes are classically associated with Rubinstein-Taybi syndrome (RTS), Menke-Hennekam syndrome presents a distinct phenotype despite involvement of the same alleles. We report 2 patients who exhibited developmental delay, intellectual disability, and dysmorphic features without typical RTS findings. Genetic analysis revealed a novel frameshift variant in EP300 in one patient and a de novo missense variant in CREBBP in the other. Long-term follow-up and increasing use of whole-exome sequencing have facilitated recognition of Menke-Hennekam syndrome as a distinct clinical entity. Reporting 2 patients with exon 31 variants in CREBBP and EP300, we aim to improve awareness and diagnostic accuracy of this rare disorder.