Two families with sibling recurrence of the 17q21.31 microdeletion syndrome due to low-grade mosaicism

Abstract

The 17q21.31 microdeletion syndrome is characterised by intellectual disability, epilepsy, distinctive facial dysmorphism, and congenital anomalies. To date, all individuals reported with this syndrome have been simplex patients, resulting from de novo deletions. Here, we report sibling recurrence of the 17q21.31 microdeletion syndrome in two independent families. In both families, the mother was confirmed to be the parent-of-origin for the 17q21.31 deletion. Fluorescence in situ hybridisation analyses in buccal mucosa cells, of the mother of family 1, identified monosomy 17q21.31 in 4/50 nuclei (8%). In mother of family 2, the deletion was identified in 2/60 (3%) metaphase and in 3/100 (3%) interphase nuclei in peripheral lymphocytes, and in 7/100 (7%) interphase nuclei in buccal cells. A common 17q21.31 inversion polymorphism predisposes to non-allelic homologous recombination and hereby to the 17q21.31 microdeletion syndrome. On the basis of the 17q21.31 inversion status of the parents, we calculated that the probability of the second deletion occurring by chance alone was 1/14 438 and 1/4812, respectively. If the inversion status of the parents of a child with the 17q21.31 microdeletion syndrome is unknown, the overall risk of a second child with the 17q21.31 microdeletion is 1/9461. We conclude that the presence of low-level maternal somatic-gonadal mosaicism is associated with the microdeletion recurrence in these families. This suggests that the recurrence risk for parents with a child with a 17q21.31 microdeletion for future pregnancies is higher than by chance alone and testing for mosaicism in the parents might be considered as a helpful tool in the genetic counselling.

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

“…13,18,20,22,30 In our cohort, we observed behavioural problems in 57% of cases. These problems included autism/autistic traits, ADHD/attention deficit/ hyperactivity, shyness, anxiety/phobias, impulsive and stereotypic behaviour, psychosis, and depression.…”

“…This study shows that haploinsufficiency of KANSL1 by itself is sufficient to cause the full KdVS phenotype, 5,20 including neonatal hypotonia, feeding difficulties, developmental delay, ID with speech delay, seizures, characteristic facial dysmorphism, musculoskeletal anomalies, congenital heart defects, renal and urogenital anomalies, and ectodermal anomalies. Although many individuals with KdVS display a social and friendly behaviour, dysfunctional neuropsychological problems are also common.…”

“…A search of the medical literature identified 23 articles describing the clinical features of 81 patients with KdVS. [1][2][3][4][5]13,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] …”

“…Borderline IQ was also described in two boys with a 17q21.31 deletion who finished secondary school with educational support. 20 However, in general the level of psychomotor delay is moderate and expressive language development seems to be particularly affected compared with receptive language or motor skills. In our cohort, 4 out of 35 informative cases (ie, age ≥ 5 years) were non-verbal (11%).…”

Williams-Beuren Syndrome:A Rare Case from Western India

“…Koolenet al 8 have also observed that the deletion of 7q11.23 is sporadic (De novo) in almost all cases. In our study, interestingly case -1 was not having any heart problems while case -2 had Supra Valvular Arotic Stenosis (SVAS).…”