Chromosome 9q34 Deletion

Yang et al. “Genotype–phenotype correlations in 9q34.3 microdeletion syndrome: a study of 35 Mainland Chinese patients”. “Orphanet Journal of Rare Diseases,” 2026, v. 21:22. 

Kleefstra syndrome is characterized by intellectual disability (ID), autism spectrum disorder, childhood hypotonia, and distinctive facial features. The majority of individuals function in the moderate-to-severe spectrum of ID. Symptoms of Kleefstra syndrome also includes various congenital anomalies like congenital heart defects, dysmorphic features, microcephaly, and renal anomalies. A diagnosis of Kleefstra syndrome is made when genetic testing reveals a heterozygous deletion at chromosome 9q34.3 that includes at least part of EHMT1 or a heterozygous intragenic EHMT1 pathogenic variant. Yang et al. expanded the genotype-phenotype correlations of Kleefstra syndrome in a cohort of 35 Chinese patients, 3 of which were fetuses (14 had 9q34.3 deletions and 21 had EHMT1 variants). The deletions ranged from 0.21 kb to 2581 kb. Genetic examination of the parents was available in 28 families, in two of these families (7%) one of the parents was the mosaic carrier of mutation in EHMT1. The authors described the following features in the current cohort: motor delay (29/30), developmental delay/intellectual disability (31/31), postnatal hypotonia (10/26), anomalies on brain MRI (12/22), chewing difficulties (10/23), autism spectrum disorder (3/14), congenital heart defect (10/26), hearing impairment (6/29), constipation (9/25), and renal anomalies (5/28). The authors report that for the first time, they observed that several patients who exhibited skin manifestations. The authors observed no difference in the prevalence of DD/ID, neurological features, congenital cardiac anomalies, genital anomalies of males, renal anomalies, and behavior issues between the 9q34.3 deletions and the EHMT1 variants. However, the authors have observed that the frequencies of everted lower lip, small and spaced teeth, short neck, and renal anomalies were significantly higher among the 9q34.3 deletions. The authors further suggest that other genes besides EHMT1 may be contributing to the multiorgan manifestations in Kleefstra syndrome caused by 9q34.3 deletions. The authors also did not observe any correlation between deletion size and severity of ID. Overall additional studies are needed to validate these findings and to better explore the genotype-phenotype correlations of Kleefstra syndrome.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. Review and formatting by Nicole Talaba, MS CGC. For more information on any article please contact info@chromodisorder.org