Expanding the phenotypic profile of Kleefstra syndrome: A female with low-average intelligence and childhood apraxia of speech

Am J Med Genet A. 2016 May;170A(5):1312-6. doi: 10.1002/ajmg.a.37575. Epub 2016 Feb 1.


Kleefstra syndrome (KS) is a rare neurogenetic disorder most commonly caused by deletion in the 9q34.3 chromosomal region and is associated with intellectual disabilities, severe speech delay, and motor planning deficits. To our knowledge, this is the first patient (PQ, a 6-year-old female) with a 9q34.3 deletion who has near normal intelligence, and developmental dyspraxia with childhood apraxia of speech (CAS). At 6, the Wechsler Preschool and Primary Intelligence testing (WPPSI-III) revealed a Verbal IQ of 81 and Performance IQ of 79. The Beery Buktenica Test of Visual Motor Integration, 5th Edition (VMI) indicated severe visual motor deficits: VMI = 51; Visual Perception = 48; Motor Coordination < 45. On the Receptive One Word Picture Vocabulary Test-R (ROWPVT-R), she had standard scores of 96 and 99 in contrast to an Expressive One Word Picture Vocabulary-R (EOWPVT-R) standard scores of 73 and 82, revealing a discrepancy in vocabulary domains on both evaluations. Preschool Language Scale-4 (PLS-4) on PQ's first evaluation reveals a significant difference between auditory comprehension and expressive communication with standard scores of 78 and 57, respectively, further supporting the presence of CAS. This patient's near normal intelligence expands the phenotypic profile as well as the prognosis associated with KS. The identification of CAS in this patient provides a novel explanation for the previously reported speech delay and expressive language disorder. Further research is warranted on the impact of CAS on intelligence and behavioral outcome in KS. Therapeutic and prognostic implications are discussed.

Keywords: 9q34 deletion syndrome; Kleefstra syndrome; childhood apraxia of speech; developmental dyspraxia; rare disease.

Publication types

  • Case Reports

MeSH terms

  • Apraxias / genetics*
  • Apraxias / physiopathology
  • Child
  • Chromosome Deletion
  • Chromosomes, Human, Pair 9 / genetics
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / physiopathology
  • Female
  • Gene Deletion
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / physiopathology
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Intelligence Tests
  • Language Development Disorders / genetics
  • Language Development Disorders / physiopathology
  • Motor Skills Disorders / genetics*
  • Motor Skills Disorders / physiopathology

Supplementary concepts

  • Kleefstra Syndrome