Mini-Review Monosomy 1p36 syndrome: reviewing the correlation between deletion sizes and phenotypes

Abstract

ABSTRACT. The major clinical features of monosomy 1p36 deletion are developmental delay and hypotonia associated with short stature and craniofacial dysmorphisms. The objective of this study was to review the cases of 1p36 deletion that was reported between 1999 and 2014, in order to identify a possible correlation between the size of the 1p36-deleted segment and the clinical phenotype of the disease. Scientific articles published in the (National Center for Biotechnology Information; NCBI http://www.ncbi.nlm. nih.gov/pubmed) and Scientific Electronic Library Online (www.scielo.com. br) databases were searched using key word combinations, such as "1p36 deletion", "monosomy 1p36 deletion", and "1p36 deletion syndrome". Articles in English or Spanish reporting the correlation between deletion sizes and the respective clinical phenotypes were retrieved, while letters, reviews, guidelines, and studies with mouse models were excluded. Among the 746 retrieved articles, only 17 (12 case reports and 5 series of cases), comprising 29 patients (9 males and 20 females, aged 0 months (neonate) to 22 years) bearing the 1p36 deletions and whose clinical phenotypes were described, met the inclusion criteria. The genotype-phenotype correlation in monosomy 1p36 is a challenge because of the variability in the size of the deleted segment, as well as in the clinical manifestations of similar size deletions. Therefore, the severity of the clinical features was not always associated with the deletion size, possibly because of the other influences, such as stochastic factors, epigenetic events, or reduced penetration of the deleted genes.

Prenatal findings in 1p36 deletion syndrome: New cases and a literature review

“…Details of each case are given in Table . The mean ± SD (range) term at the time of diagnosis was 19 ± 5.6 weeks of gestation, and the mean ± SD (range) maternal age was 29.2 ± 6.7 (19‐42). In all cases, the indication for an invasive procedure (CVS in four cases and amniocentesis in six) was the presence of abnormal ultrasound findings: nuchal translucency greater than 3.5 mm (n = 4), a structural brain abnormality (hypoplasic corpus callosum, n = 2), ventricular dilatation (n = 3), retrognathia suggesting a Pierre‐Robin sequence (n = 2), and a cardiac defect (n = 1).…”

“…Establishing a genotype‐phenotype correlation in monosomy 1p36 is a challenge because of (a) the variability in the size of the deletion and (b) phenotypic differences between cases with similar‐sized deletions. Indeed, the severity of the clinical features is not always related to the deletion size—suggesting that other factors (such as stochastic factors, epigenetic events, or reduced penetration of the deleted genes) have a role . Better knowledge of the genotype‐phenotype correlation would enable more accurate, individualized prognostic counseling.…”

“…Indeed, the severity of the clinical features is not always related to the deletion size-suggesting that other factors (such as stochastic factors, epigenetic events, or reduced penetration of the deleted genes) have a role. 10 Better knowledge of the genotype-phenotype correlation would enable more accurate, individualized prognostic counseling. To date, candidate genes that might contribute to these phenotypes have been proposed on the basis of their expression pattern, putative function, or the phenotypes seen in animal models and/or individuals who carry harmful mutations.…”

Electroclinical features of epilepsy monosomy 1p36 syndrome and their implications

“…This could be explained by mechanisms such as stochastic or epigenetic factors, and/or the lack of complete penetrance of the gene, which could influence the clinical picture and the precise phenotype-genotype correlation. 23 One possible explanation of the emergence of dele- Fisher's exact test 2 by 2. *P = 0.0225.…”

“…As the terminal region of chromosome 1p is gene-rich, multiple genes may contribute to the various phenotypic features in this syndrome 2,4,15,21. This could be explained by mechanisms such as stochastic or epigenetic factors, and/or the lack of complete penetrance of the gene, which could influence the clinical picture and the precise phenotype-genotype correlation 23. The functional loss of one KCNAB2 allele decreases the threshold for seizures, by reducing potassium channel-mediated membrane repolarization and increasing neuronal excitability 2.…”