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

Abstract

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.

Adaptive and maladaptive functioning in Kleefstra syndrome compared to other rare genetic disorders with intellectual disabilities

“…KS is a rare ID syndrome, caused by EHMT1 haploinsufficiency (Kleefstra et al, 2006). KS patients function in the range from a moderate to profound ID, rarely on a mild ID to borderline IQ (Bock et al, 2016;Samango-Sprouse et al, 2016). Several KS case reports mention autistic features, regression, and sleep problems (Schmidt, Nag, Hunn, Houge, & Hoxmark, 2016;Verhoeven, Egger, Vermeulen, van de Warrenburg, & Kleefstra, 2011;Verhoeven, Kleefstra, & Egger, 2010;Vermeulen et al, 2015).…”

Case Report: A Case Study on the Neurodevelopmental Profile of a Child With Pallister–Killian Syndrome and His Unaffected Twin

“…Consistent with AF's childhood apraxia of speech (CAS), motor planning difficulties are at the root of CAS and are often associated with neurogenetic disorders ( 23 – 25 ). These motor planning issues coupled with hypotonia often cause dysfunction with the orofacial musculature, resulting in difficulties shaping the muscles to articulate the desired production ( 24 ).…”

A Gene-Based Algorithm for Identifying Factors That May Affect a Speaker’s Voice

“…31 (DRD3, ZBTB20 ‡ , GAP43, LSAMP) † ‡ OMIM: 615433; Cytogenetic location: 3q13.31 Genomic coordinates (GRCh38): 3:113,700,000-117,600,000 Names: Chromosome 3q13. 31 Delayed speech [27], Apraxia [28] and Absent speech Delayed speech [34]; Impaired speech [35] Dysarthric speech, absent speech [36]; impaired speech [37] 11q23. 3…”