Deletion of the distal long arm of chromosome 10; is there a characteristic phenotype? A report of 15 de novo and familial cases

Abstract

It has been suggested previously that patients with terminal deletions of chromosome 10q have a recognizable phenotype including a characteristic facial appearance combined with other abnormalities including mental retardation, cardiac and anogenital anomalies. We report the largest published series of new cases of terminal 10q deletion, including eight familial and four de novo cases and three cases with interstitial deletions involving chromosome bands 10q25.2-26.3. The deleted regions were defined by FISH using YAC probes, as well as standard karyotyping. The most consistent clinical features in our cases are cranial anomalies including facial asymmetry, prominent nose and nasal bridge, prominent ears, thin upper lip, along with growth retardation, developmental delay, and digital abnormalities. Visceral abnormalities were only identified in a small number of the patients, with renal involvement in three cases and structural cardiac malformations in two others. Learning difficulties of varying severity were found in 11 cases and behavioral problems described in four. Candidate genes for behavioral and learning difficulties within the deleted region include Calcyon. Other genes in the region that might have a role in causing the phenotype include the genes coding for fibroblast growth factor receptor type 2 (FGFR2) and C-terminal binding protein 2 (CTBP2).

The future of prenatal diagnosis: rapid testing or full karyotype? An audit of chromosome abnormalities and pregnancy outcomes for women referred for Down's Syndrome testing

“…This is consistent with previous observations of phenotypic variability in individuals with small terminal deletions of chromosome 10q. 19 Although the outcome in case 15 could not be ascertained, this karyotype (trisomy 16) when found at CVS is associated with a high risk of IUGR, reduced birthweight and fetal malformation.…”

Molecular and clinical analyses with neuropsychological assessment of a case of del(10)(q26.2qter) without intellectual disability: Genomic and transcriptomic combined approach and review of the literature

“…Frequent findings of individuals with subtelomeric deletion 10q (present in !50%), include low birthweight, microcephaly at birth, short stature in childhood/adulthood, characteristic facial dysmorphism, intellectual disability, and behavioral problems (summed up for 21 patients of the literature in Table I) [Irving et al, 2003;Courtens et al, 2006;Miller et al, 2009;Yatsenko et al, 2009;Iourov et al, 2014] . On the basis of genomics arrays data, previous efforts to establish genotype-phenotype correlations proposed a 600 kb minimal critical region encompassing the C10orf90 and DOCK1 genes.…”

“…Common clinical findings include psychomotor delay/ intellectual disability with hypotonia, pre-and post-natal growth retardation, congenital heart disease, genital/ urinary tract anomalies, microcephaly, and mild facial dysmorphism [Courtens et al, 2006]. We decided to focus our interest on the subtelomeric deletion 10q26 (clinical data summed up for 21 patients of the literature in Table I) [Irving et al, 2003;Courtens et al, 2006;Miller et al, 2009;Yatsenko et al, 2009;Iourov et al, 2014]. On a molecular level, the haploinsufficiency of the DOCK1, C10orf90, and CALY genes have been discussed as …”

Novel interstitial deletion of 10q24.3–25.1 associated with multiple congenital anomalies including lobar holoprosencephaly, cleft lip and palate, and hypoplastic kidneys

“…Deletions of the distal end of 10q have been associated with common characteristics, such as dysmorphic facial features, intellectual disability, hypotonia, growth retardation, congenital heart disease, and urogenital abnormalities [Irving et al, 2003], although there is significant clinical variability between patients. There have been reports of individuals with more proximal chromosome 10q deletions manifesting features of single gene syndromes relating to one of the deleted genes; for example Renal Coloboma syndrome (RCS) in a patient with a 10q24.3-q25.1 deletion encompassing PAX2 [Hoefele et al, 2012] and patients with 10q23 deletions with an Infantile Juvenile Polyposis syndrome with deletions encompassing the BMPR1A and PTEN genes [Menko et al, 2008].…”