Expanding the Neurological Phenotype of Ring Chromosome 10 Syndrome: A Case Report and Review of the Literature

Abstract

Ring chromosome 10 [r(10)] syndrome is a rare genetic condition, currently described in the medical literature in a small number of case report studies. Typical clinical features include microcephaly, short stature, facial dysmorphisms, ophthalmologic abnormalities and genitourinary malformations. We report a novel case of r(10) syndrome and review the neurological and neuroradiological phenotypes of the previously described cases. Our patient, a 3 year old Italian girl, represents the 20th case of r(10) syndrome described to date. Intellectual disability/developmental delay (ID/DD), microcephaly, strabismus, hypotonia, stereotyped/aggressive behaviors and electroencephalographic abnormalities were identified in our patient, and in a series of previous cases. A brain MRI disclosed a complex malformation involving both the vermis and cerebellar hemispheres; in the literature, posterior cranial fossa abnormalities were documented by CT scan in another case. Two genes deleted in our case (ZMYND11 in 10p and EBF3 in 10q) are involved in autosomal dominant neurodevelopmental disorders, characterized by different expressions of brain and posterior cranial fossa abnormalities, ID/DD, hypotonia and behavioral problems. Our case expands the neurological and neuroradiological phenotype of r(10) syndrome. Although r(10) syndrome represents an extremely rare condition, with a clinical characterization limited to case reports, the recurrence of specific neurological and neuroradiological features suggests the need for specific genotype-phenotype studies.

Transgenic mice overexpressing mutant TDP-43 show aberrant splicing of autism associated geneZmynd11prior to onset of motor symptoms

“…Therefore, for the purpose of this study, 50-day old (pre-symptomatic) and 100-day old animals (post-symptomatic) were classified into respective groups, to represent stages of the disease. Among the aberrantly spliced genes, zinc finger, MYND typecontaining 11 ( Zmynd11 ) is of particular interest due to its recent implications in autism-related motor delay (Moskowitz, Belnap et al 2016); intellectual disability (Pruccoli, Graziano et al 2021) and brain atrophy and ataxia (Indelicato, Zech et al 2022). In addition, Zmynd11/ZMYND11 has been previously reported to be an RNA binding partner of TDP-43 in the mouse brain (Narayanan, Mangelsdorf et al 2013), rat cortical neurons (Sephton, Cenik et al 2010) and post-mortem human brain (Tollervey, Curk et al 2011) and was reported to be aberrantly spliced in the spinal cord of sporadic ALS patients with TDP-43 pathology (Rabin, Kim et al 2010).…”