ABSTRACT
OBJECTIVE: Non-invasive prenatal screening (NIPS) utilizes circulating cell-free DNA (cfDNA) to screen for fetal genetic abnormalities. NIPS is the first widely-available prenatal screen to assess genotypic sex. Most pediatricians have limited familiarity with NIPS technology and potential etiologies of discordant results. Increased familiarity may provide diagnostic insight and improve clinical care. STUDY DESIGN: We reviewed all patients with discordant genotypic fetal sex assessed by cfDNA and neonatal phenotypic sex referred to our medical center. RESULT: Four infants with discordant cfDNA result and phenotypic sex were identified. Etiologies include vanishing twin syndrome, difference of sexual development, sex chromosome aneuploidy and maternal chimerism. CONCLUSIONS: We present four cases illustrating potential etiologies of discordant cfDNA result and postnatal phenotypic sex. Unanticipated cfDNA results offer the perinatologist a unique opportunity for early diagnosis and targeted treatment of various conditions, many of which may not have otherwise been detected in the perinatal period.
Subject(s)
Cell-Free Nucleic Acids/analysis , Disorders of Sex Development/diagnosis , Prenatal Diagnosis/methods , Sex Determination Analysis/methods , Sex , Adult , Early Diagnosis , Female , Genetic Testing/methods , Humans , Infant, Newborn , Liquid Biopsy/methods , Male , PregnancyABSTRACT
OBJECTIVES: To explore the advantages and limitations of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of a fetus with anomalies and a chromosome abnormality. METHODS: We used karyotype analysis, FISH and array CGH to investigate an unbalanced chromosome rearrangement. RESULTS: We report a case of a fetus with ultrasound anomalies at 11 weeks' gestation and an unbalanced chromosome translocation [46,XX,der(13)t(2;13)(p25.1;q32)pat]. Initially, a chromosome 13 deletion was reported from G-banded chromosome analysis and 13q subtelomere FISH. The involvement of chromosome 2 was determined after a balanced translocation was identified in the father, 46,XY,t(2;13)(p25.1;q32). Array CGH confirmed the fetal abnormality as partial trisomy of the short arm chromosome 2 and partial monosomy of the long arm of chromosome 13. The abnormalities identified by ultrasound studies and autopsy appear to be most consistent with 13q deletion syndrome. CONCLUSIONS: Array CGH successfully identified a subtle unbalanced chromosome complement in a fetus with multiple ultrasound anomalies. If array CGH had been performed along with the fetal karyotype, the cryptic partial trisomy 2 could have been identified in a more timely manner to assist in the prenatal counseling of this family.
Subject(s)
Chromosome Disorders/diagnostic imaging , Fetal Diseases/diagnostic imaging , Lymphangioma, Cystic/genetics , Prenatal Diagnosis/methods , Translocation, Genetic , Adult , Chromosome Disorders/genetics , Chromosome Disorders/pathology , Chromosomes, Human, Pair 13 , Comparative Genomic Hybridization , Female , Fetal Diseases/genetics , Fetal Diseases/pathology , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Lymphangioma, Cystic/diagnostic imaging , Pregnancy , Ultrasonography, PrenatalABSTRACT
OBJECTIVE: To explore the utility of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of microphthalmia and linear skin defects syndrome. METHODS: We used karyotype analysis, FISH and array CGH to investigate an X;Y translocation. Replication studies were done on cultured amniocytes and lymphoblasts. RESULTS: We describe a severe case of MLS syndrome that presented prenatally with multiple anomalies including cystic hygroma, microphthalmia, intrauterine growth restriction and a complex congenital heart defect. Cytogenetic analysis of amniocytes revealed an unbalanced de novo translocation between chromosomes X and Y [karyotype 46,X,der(X)t(X;Y)(p22.3;q11.2).ish der(X)(DXZ1+,DMD+,KAL-,STS-,SRY-),22q11.2 (Tuple1 x 2)]. MLS diagnosis was made at birth and the prenatal karyotype was confirmed. Replication studies showed the derivative X chromosome was the inactive X. Array CGH confirmed the X and Y imbalances seen in the karyotype and also showed twelve BACs in the MLS region were deleted as a result of the translocation. FISH with BAC clones verified the array findings and placed the X breakpoint in Xp22.2, resulting in the amended karyotype, 46,X,der(X)t(X;Y)(p22.2;q11.2).ish der(X)(DXZ1+,DMD+,KAL-,STS-,SRY-),22q11.2(Tuple1 x 2) arr cgh Xp22.33p22.2(LLNOYCO3M15D10 -->GS1-590J6)x 1,Yq11.222q23(RP11-20H21-->RP11-79J10)x 1. CONCLUSION: The sensitivity of array CGH was valuable in detecting monosomy of the MLS critical region. Array CGH should be considered for the prenatal diagnosis of this syndrome.
