A child with multiple congenital anomalies due to partial trisomy 7q22.1 → qter resulting from a maternally inherited balanced translocation: a case report and review of literature

Abstract

Background: Parental balanced reciprocal translocations can result in partial aneuploidies in the offspring due to unbalanced meiotic segregation during gametogenesis. Herein, we report the phenotypic and molecular cytogenetic characterization of a 2 years and 4 months old female child with partial trisomy 7q22 → qter. This is the first such reported case resulting from a parental balanced translocation involving the long arms of chromosomes 7 and 14. The phenotype of the proband was compared with that of previously reported cases of trisomy 7q21 → qter or 7q22 → qter resulting from parental balanced translocations.

Case presentation: The proband was born pre-term to a 34-year-old mother with a history of two first trimester miscarriages and an early infant death. She was referred at the age of 8 months for genetic evaluation due to prenatal and postnatal growth retardation, developmental delay and multiple congenital anomalies. On clinical evaluation, she had craniofacial dysmorphic features such as scaphocephaly, large anterior fontanelle with open posterior fontanelle, prominent occiput, triangular face, high forehead, hypertelorism, down slanting eyes, flat nasal bridge, small nose, low set ears, micro-retrognathia, high arched palate and short neck. Cranial computerized tomography scan showed lateral ventriculomegaly with features of early cerebral atrophy. Conventional cytogenetic analysis showed the karyotype 46,XX,der(14)t(7;14)(q22;q32)mat in the proband due to an unbalanced segregation of a maternal balanced translocation t(7;14)(q22;q32). Fluorescence in-situ hybridization analysis confirmed the partial trisomy 7q22 → qter in the proband with a minimal loss of genetic material on chromosome 14. Single nucleotide polymorphism array further confirmed the duplication on chromosome 7q22.1 → qter and a small terminal deletion on chromosome 14q32.3 → qter.

Conclusion: We report the longest-surviving child with trisomy 7q22 → qter due to a parental balanced translocation between chromosomes 7 and 14. Clinical features observed in the proband were consistent with the consensus phenotype of partial trisomy 7q22 → qter reported in the scientific literature. Early diagnosis of these patients using molecular cytogenetic techniques is important for establishing the precise diagnosis and for making decisions pertaining to the prognostication and management of affected individuals.

Keywords: Congenital malformations; Fluorescence in-situ hybridization; SNP array; Translocation (7;14); Trisomy 7q.

Fig. 1

Pedigree of the proband. T1MC- first trimester miscarriage; Age- y: years, m: months

Fig. 2

Facial photograph of the proband (frontal view) showing dysmorphic features such as triangular face, high forehead, hypertelorism, down slanting eyes, flat nasal bridge, small nose and low set ears

Fig. 3

Karyograms (a) of the proband showing the derivative chromosome 14 and the normal chromosome 14 with the ideogram (b) of the proband’s mother showing the reciprocal translocation between chromosomes 7 and 14 with ideograms and the breakpoint on each chromosome

Fig. 4

FISH analysis of the proband (a) Using the XL 7q22/7q36 locus specific probe (Metasystems, Altlussheim, Germany) showing hybridization signals on two normal chromosomes 7 and on the derivative chromosome 14 (indicated by the arrowhead) on metaphase chromosomes [Right] and on interphase chromosomes [Left]; Orange labelled probe hybridizes to 7q22 region including the MLL5 gene. Green labelled probe hybridizes to 7q36 region that includes EZH2 gene. b Using XL IGH plus probe (Metasystems, Altlussheim, Germany) hybridizing to constant region (orange) and variable distal region (green) of the IGH locus on chromosome 14 (14q32). Analysis shows normal hybridization signals on normal chromosome 14 and derivative chromosome 14 (indicated by the arrowhead) in metaphase chromosomes [Left] and interphase chromosomes [Right]

Fig. 5

SNP array results of the proband (a) Full genome view of the proband, chromosome 7 duplication is circled. b Full view of chromosome 7. Top plots: Log R ratio representing the intensity data or the copy number, Bottom plots: B allele frequency