| Autor: |
Brar, Bobby K., Blakemore, Karin, Hertenstein, Christine, Miller, Jena L., Miller, Kristen A., Shamseldin, Hanan, Maddirevula, Sateesh, Hays, Thomas, Lianoglou, Billie, Dukhovny, Stephanie, Baker, Linda A., Sparks, Teresa N., Wapner, Ronald, Alkuraya, Fowzan S., Norton, Mary E., Jelin, Angie C. |
| Zdroj: |
Prenatal Diagnosis; Feb2024, Vol. 44 Issue 2, p196-204, 9p |
| Abstrakt: |
Objective: Fetal megacystis generally presents as suspected lower urinary tract obstruction (LUTO), which is associated with severe perinatal morbidity. Genetic etiologies underlying LUTO or a LUTO—like initial presentation are poorly understood. Our objectives are to describe single gene etiologies in fetuses initially ascertained to have suspected LUTO and to elucidate genotype‐phenotype correlations. Methods: A retrospective case series of suspected fetal LUTO positive for a molecular diagnosis was collected from five centers in the Fetal Sequencing Consortium. Demographics, sonograms, genetic testing including variant classification, and delivery outcomes were abstracted. Results: Seven cases of initially prenatally suspected LUTO‐positive for a molecular diagnosis were identified. In no case was the final diagnosis established as urethral obstruction that is, LUTO. All variants were classified as likely pathogenic or pathogenic. Smooth muscle deficiencies involving the bladder wall and interfering with bladder emptying were identified in five cases: MYOCD (2), ACTG2 (2), and MYH11 (1). Other genitourinary and/or non‐genitourinary malformations were seen in two cases involving KMT2D (1) and BBS10 (1). Conclusion: Our series illustrates the value of molecular diagnostics in the workup of fetuses who present with prenatally suspected LUTO but who may have a non‐LUTO explanation for their prenatal ultrasound findings. Key points: What is already known about this topic?Lower urinary tract obstruction (LUTO) presents prenatally with fetal megacystis, a thickened bladder wall, and possible signs of upper urinary tract obstructionLUTO is seen at an increased prevalence in cases of aneuploidySome cases initially suspected to be LUTO prenatally represent other disorders distinctly different from simple urethral obstruction What does this study add?Heterozygous and homozygous variants in several single genes, including MYOCD, ACTG2, MYH11, KMT2D, and BBS10, may be identified in prenatally suspected LUTO, which does not represent a simple anatomic urethral obstruction but rather a functional smooth muscle deficiency disorder or a multiple malformation syndromeMutations in MYOCD and ACTG2 are associated with a LUTO—like picture prenatally and failure of bladder emptying (FOBE). Familial cases can demonstrate variable expressivity, incomplete penetrance, and sex‐dependent phenotypesEuploid fetuses with prenatally suspected LUTO and non‐genitourinary malformations are likely to have a higher frequency of single gene etiologiesA molecular diagnosis can provide clarity in cases presenting initially with suspected LUTO and assists not only in counseling regarding recurrence risks and reproductive planning but also in clarifying the underlying mechanism for failure of bladder emptying and, thereby, counseling regarding prognosis and management [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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