Introduction

Ring chromosome 10 [r(10)] is a rare genetic condition that can be associated with a terminal 10q deletion and a terminal 10p deletion, and mosaicism for monosomy 10 or double r(10). To date, at least 17 clinical reports have been described [ ]. Typical clinical abnormalities associated with r(10) include intellectual disability, developmental delay, microcephaly, short stature, facial dysmorphisms, ophthalmologic abnormalities and genitourinary malformations [ ]. Prenatal diagnosis of r(10) is very rare. To our knowledge, only one case has been reported in association of talipes equinovarus on fetal ultrasound [ ]. Here, we present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for r(10) and monosomy 10 at amniocentesis in a fetus associated with perinatal growth restriction but no gross structural abnormalities.

Case report

A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,XX,-10[11]/46,XX,r(10)[6]. Prenatal ultrasound was normal. She was referred for genetic counseling, and repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46,XX,r(10)[15]/45,XX,-10[5]. The parental karyotypes were normal. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed a 2.182-Mb 10p15.3 deletion encompassing the genes of ZMYND11 and DIP2C , and a 2.257-Mb 10q26.3 deletion outside the genes of DOCK1 and EBF3 ( Fig. 1 ). Prenatal ultrasound showed intrauterine growth restriction but no gross structural abnormalities. The parents elected to continue the pregnancy, and a 2425-g baby was delivered at 40 weeks of gestation without craniofacial dysmorphism. The cord blood had a karyotype of 46,XX,r(10)[29]/45,XX,-10[9]/47,XX,r(10),+r(10)[1]/46,XX[1] ( Fig. 2 ). When follow-up at age four months, the peripheral blood had a karyotype of 46,XX,r(10)[32]/45,XX,-10[8], her body weight was 5.1 Kg (<3 centile), and body height was 58 cm (<3 centile). She did not have craniofacial dysmorphism. When follow-up at age one year and two months, her body weight was 5.9 Kg (<3 centile), and body height was 68.5 cm (<3 centile). She manifested motor and speech developmental delay but no hypotonia. Brain computed tomography and whole-body ultrasound examination showed no abnormalities.

(A), (B) and (C) Array comparative genomic hybridization (aCGH) on the DNA extracted from the uncultured amniocytes using SurePrint G3 Unrestricted CGH ISCA v2, 8′60 K (Agilent Technologies, Santa Clara, CA, USA) shows the result of arr 10p15.3 (136,361–2,318,431)´1.0, arr 10q26.3 (133,177,546–135,434,178)´1.0 [GRCh37 (hg19)] with a 2.182-Mb 10p15.3 deletion encompassing the genes of ZMYND11 and DIP2C and a 2.257-Mb 10q26.3 deletion outside the genes of DOCK1 and EBF3 .

(A) A karyotype of 46,XX,r(10), (B) a karyotype of 45,XX,-10, (C) a karyotype of 47,XX,r(10),+r(10) and (D) a karyotype of 46,XX. r = ring chromosome. The arrows in the normal chromosome 10 indicate the points of break and reunion.

Discussion

The present case was associated with de novo mosaic r(10)/monosomy 10 at amniocentesis but without gross structural abnormality and was diagnosed because of advanced maternal age. In the present case, the first amniocentesis at 17 weeks of gestation revealed a karyotype of 45,XX,-10[11]/46,XX,r(10)[6], consistent with 65 % mosaicism for monosomy 10 and 35 % mosaicism for r(10). However, repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46,XX,r(10)[15]/45,XX,-10[5], consistent with 75 % mosaicism for r(10) and 25 % mosaicism for monosomy 10. At birth, the cord blood had a karyotype of 46,XX,r(10)[29]/45,XX,-10[9]/47,XX,r(10),+r(10)[1]/46,XX[1], consistent with 72.5 % mosaicism for r(10), 22.5 % mosaicism for monosomy 10, 2.5 % mosaicism for double r(10) and 2.5 % mosaicism for 46,XX. At age four months, the peripheral blood had a karyotype of 46,XX,r(10)[32]/45,XX,-10[8], consistent with 80 % mosaicism for r(10) and 20 % mosaicism for monosomy 10. The peculiar aspect of the present case is perinatal progressive increase of the r(10) and progressive decrease of the monosomy 10. The appearance of 46,XX in 1/40 cells in the cord blood lymphocytes was especially uncommon. However, during follow-up at age four months, no cell with a normal karyotype of 46,XX could be observed.

The present case has a 2.182-Mb 10p15.3 deletion encompassing ZMYND11 and DIP2C . Clinical reports of distal 10p deletion have been well described [ ]. Chromosome 10p15.3 microdeletion syndrome is characterized by neurodevelopmental disorder, characteristic dysmorphic features, behavioural disturbances, cognitive/developmental delay, speech delay, motor delay, brain anomalies, seizures, low birth weight and short stature, and in most cases the genes of ZMYND11 and DIP2C are deleted [ ]. Tumiene et al. [ ] suggested that the ZMYND11 is the critical gene responsible for chromosome 10p15.3 microdeletion syndrome. Deletions and mutations of ZMYND11 (OMIM 608668) are associated with autosomal dominant intellectual developmental disorder-30 (OMIM 616083).

The present case has a 2.257-Mb 10q26.3 deletion without the involvement of DOCK1 and EBF3 and no hypotonia. Clinical reports of distal 10q deletion have been well reported [ ]. The chromosome 10q26 deletion syndrome (OMIM 609625) is a clinical well-defined syndrome that is characterized by intellectual disability, developmental and growth delay, microcephaly, hypotonia, facial dysmorphism of prominent nasal bridge, hypertelorism and low-set ears, and less common features of digital anomalies, hearing loss, urogenital malformations and congenital heart defects [ , , ]. In the present case, there was no deletion of DOCK1 and EBF3 . Yatsenko et al. [ ] suggested that haploinsufficiency of DOCK1 is responsible for the chromosome 10q26 deletion syndrome. Deletions and mutations of EBF3 (OMIM 607407) is associated with autosomal dominant hypotonia, ataxia and delayed development syndrome (OMIM 617330).

In summary, we report prenatal diagnosis and molecular cytogenetic characterization of mosaicism for r(10) and monosomy 10 at amniocentesis in a fetus with a 10p15.3 microdeletion and a 10q26.3 microdeletion. Mosaicism for r(10) and monosomy 10 at prenatal diagnosis can be associated with perinatal growth restriction but no gross structural abnormalities.