The first Brazilian clinical report of Kleefstra syndrome, including semicircular canals agenesis as a possible phenotype expansion

Eur J Med Genet. 2024 Oct:71:104966. doi: 10.1016/j.ejmg.2024.104966. Epub 2024 Aug 13.

Abstract

Objective: to report the first case series of Brazilian children diagnosed with Kleefstra syndrome, present a possible phenotype expansion to the syndrome and to raise physicians' awareness for this rare disease.

Results: seven patients with confirmed KS were evaluated, including 5 males and 2 females. Abnormal prenatal findings were observed in 4 patients. Most patients were born at term, with normal birth measurements. All patients had neurodevelopmental delay and 6 evolved with intellectual disability. Hearing loss was present in 57.1% of patients and 28.7% had congenital heart disease. In males, cryptorchidism was present in 75%. Despite the facial dysmorphisms, only 2 out of 7 patients had a pre-test clinical suspicion of KS. One specific patient presented bilateral agenesis of the semicircular canals, a very rare ear manifestation in Kleefstra syndrome, representing a possible phenotype expansion of the syndrome.

Conclusion: this report aims to promote awareness among physicians evaluating patients in a context of neurodevelopmental delay or congenital malformations, especially congenital heart defects. We also highlight a possible phenotype expansion of the syndrome, with a case of semicircular anomaly, not reported in this syndrome so far.

Keywords: 9q34.3 microdeletion; Agenesis of the semicircular canals; EHMT1; Kleefstra syndrome.

Publication types

  • Case Reports

MeSH terms

  • Brazil
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 9 / genetics
  • Craniofacial Abnormalities* / genetics
  • Craniofacial Abnormalities* / pathology
  • Female
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / pathology
  • Humans
  • Infant
  • Intellectual Disability* / genetics
  • Intellectual Disability* / pathology
  • Male
  • Phenotype*
  • Semicircular Canals* / abnormalities
  • Semicircular Canals* / pathology

Supplementary concepts

  • Kleefstra Syndrome