Tai-Heng Chen1, Xia Tian2, Pao-Lin Kuo3, Hui-Ping Pan4, Lee-Jun C Wong2,5, Yuh-Jyh Jong6,7,8. 1. Division of Pediatric Emergency, Department of Emergency, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. Baylor Genetics, Houston, TX, USA. 3. Departments of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, Taiwan. 4. Center for Medical Genetics, National Cheng Kung University Hospital, Tainan, Taiwan. 5. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. 6. Departments of Pediatrics and Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 7. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 8. Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
Abstract
BACKGROUND: Fetal akinesia deformation sequence (FADS) refers to a broad spectrum of disorder with the absent fetal movement as the unifying feature. The etiology of FADS is heterogeneous, and the majority remains unknown. Prenatal diagnosis of FADS because of neuromuscular origin has relied on clinical features and fetal muscle pathology, which can be unrevealing. The recent advance of next-generation sequencing (NGS) can provide definitive molecular diagnosis effectively. METHODS AND RESULTS: An 18-week-old fetus presented with akinesia and multiple contractures of joints. The mother had two previously aborted similarly affected fetuses. Clinical diagnosis of FADS was made. Molecular diagnosis using cord blood by NGS of genes related to neuromuscular diseases revealed two compound heterozygous mutations; c.602G > A(p.W201*) and c.1516A > C(p.T506P), in the Kelch-like 40 (KLHL40) gene. Based on this information, prenatal diagnosis was performed on the CVS of the subsequent pregnancy that resulted in an unaffected female baby, heterozygous for the c.1516A > C(p.T506P) mutation. CONCLUSION: Identification of KLHL40 mutations in one of the aborted fetuses provided a confirmative diagnosis of FADS, facilitating the prenatal diagnosis of the subsequent pregnancy. This report underscores the importance of target NGS in providing FADS families with an affordable, precise molecular diagnosis for genetic counseling and options of prenatal diagnosis.
BACKGROUND:Fetal akinesia deformation sequence (FADS) refers to a broad spectrum of disorder with the absent fetal movement as the unifying feature. The etiology of FADS is heterogeneous, and the majority remains unknown. Prenatal diagnosis of FADS because of neuromuscular origin has relied on clinical features and fetal muscle pathology, which can be unrevealing. The recent advance of next-generation sequencing (NGS) can provide definitive molecular diagnosis effectively. METHODS AND RESULTS: An 18-week-old fetus presented with akinesia and multiple contractures of joints. The mother had two previously aborted similarly affected fetuses. Clinical diagnosis of FADS was made. Molecular diagnosis using cord blood by NGS of genes related to neuromuscular diseases revealed two compound heterozygous mutations; c.602G > A(p.W201*) and c.1516A > C(p.T506P), in the Kelch-like 40 (KLHL40) gene. Based on this information, prenatal diagnosis was performed on the CVS of the subsequent pregnancy that resulted in an unaffected female baby, heterozygous for the c.1516A > C(p.T506P) mutation. CONCLUSION: Identification of KLHL40 mutations in one of the aborted fetuses provided a confirmative diagnosis of FADS, facilitating the prenatal diagnosis of the subsequent pregnancy. This report underscores the importance of target NGS in providing FADS families with an affordable, precise molecular diagnosis for genetic counseling and options of prenatal diagnosis.
Authors: Dongmei Liu; Jiali Yu; Xin Wang; Yang Yang; Li Yu; Shi Zeng; Ming Zhang; Ganqiong Xu Journal: Front Pediatr Date: 2022-07-19 Impact factor: 3.569