Case Report: Two New Cases of Chromosome 12q14 Deletions and Review of the Literature

Abstract

Interstitial deletions on the long arm of chromosome 12 (12q deletions) are rare, and are associated with intellectual disability, developmental delay, failure to thrive and congenital anomalies. The precise genotype-phenotype correlations of different deletions has not been completely resolved. Ascertaining individuals with overlapping deletions and complex phenotypes may help to identify causative genes and improve understanding of 12q deletion syndromes. We here describe two individuals with non-overlapping 12q14 deletions encountered at our clinical genetics outpatient clinic and perform a review of all previously published interstitial 12q deletions to further delineate genotype-phenotype correlations. Both individuals presented with a neurodevelopmental disorder with various degrees of intellectual disability, failure to thrive and dysmorphic features. Previously, larger deletions overlapping large parts of the deletions encountered in both individuals have been described. Whereas, individual 1 seems to fit into the previously described phenotypic spectrum of the 12q14 microdeletion syndrome, individual 2 displays more severe neurological symptoms, which are likely caused by haploinsufficiency of the BAF complex member SMARCC2, which is included in the deletion. We furthermore perform a review of all previously published interstitial 12q deletions which we found to cluster amongst 5 regions on chromosome 12, to further delineate genotype-phenotype correlations, and we discuss likely disease relevant genes for each of these deletion clusters. Together, this expands knowledge on deletions on chromosome 12q which might facilitate patient counseling. Also, it illustrates that re-analysis of previously described microdeletions syndromes in the next generation sequencing era can be useful to delineate genotype-phenotype correlations and identify disease relevant genes in individuals with neurodevelopmental disorders.

Fetal Nasal Bone Hypoplasia in the Second Trimester as a Marker of Multiple Genetic Syndromes

“…Further, 12q14 microdeletion syndrome is a rare condition, characterized by low birth weight, failure to thrive, short stature, learning disabilities and osteopoikilosis [ 21 ]. In our present group, deletion 12q14.3q21.1 was associated with nasal bone hypoplasia, ventriculomegaly, hyperechogenic kidneys and two-vessel umbilical cord.…”

Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss

“…Multiple studies have described that chromosome 12 deletions are uncommon but are linked to ID, developmental delay, growth retardation and dysmorphic features ( James et al, 2005 ; Adam et al, 2010 ; Lynch et al, 2011 ; Labonne et al, 2016 ; Deng et al, 2021 ). Unlike previously documented CNVs, the specific abnormalities identified in our patients were not found in established databases such as the DGV, dbVar, Gene2Phenotype, or DisGeNet.…”

Mild intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss: A case report

“…Multiple studies have described that chromosome 12 deletions are uncommon but are linked to intellectual disability, developmental delay, growth retardation and dysmorphic features (32)(33)(34)(35)(36). In the DECIPHER database (37), a highly similar copy number loss (DECIPHER 501071, chr12:27,895,481 − 30,065,521) was reported to be responsible for short stature in one patient.…”

“…Intellectual disability (ID) is characterized by signi cant impairments in both intellectual and adaptive functioning, which refers to the ability to learn, reason, and solve problems, and functioning in conceptual, social, and practical domains (1). According to intelligence quotient (IQ) scores, severity is classi ed into mild (IQ 50-69), moderate (IQ [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49], severe (IQ [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and profound (IQ 0-19). Between 1% and 3% of the global population is affected by this type of developmental disorder (2,3); of all cases, approximately 85% are classi ed as having mild severity (4).…”