2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Identification of a pathogenic variant in NSDHL in a patient with congenital high airway obstruction (CHAOS) syndrome

Identification of a pathogenic variant in NSDHL in a patient with congenital high airway obstruction (CHAOS) syndrome
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This case study discusses the identification of a pathogenic variant in the NSDHL gene in a patient with Congenital High Airway Obstruction (CHAOS) syndrome. The patient had prenatal findings of echogenic lungs and enlarged fetal chest, as well as airway obstruction at the level of the larynx on MRI. They were delivered via EXIT procedure and had multiple clinical findings, including pulmonary complications and ichthyosiform skin lesions. Cytogenetic and molecular testing confirmed a de novo pathogenic variant in the NSDHL gene. The patient was discharged home at 4 weeks of life, with improvement of skin findings using topical therapy. This case is significant as it expands the understanding of genotype and phenotype correlations in NSDHL-related disorders and describes the prenatal phenotype of CHAOS in NSDHL-related conditions. It also demonstrates the potential benefit of exome sequencing in identifying genetic abnormalities during the prenatal period. CHAOS is a rare congenital anomaly primarily caused by laryngeal or tracheal atresia. It can lead to pulmonary hypoplasia, fetal ascites, and fetal hydrops. Delivery planning for CHAOS involves multidisciplinary approaches, including the use of Ex-Utero Intrapartum Treatment (EXIT). The NSDHL gene is involved in cholesterol biosynthesis and has an X-linked inheritance pattern. Variants in this gene are typically de novo and are associated with CHILD syndrome, which presents with icthyosiform skin lesions, limb defects, and other anomalies. In conclusion, this case highlights the importance of early identification and management of CHAOS, as well as the role of genetic testing in understanding underlying genetic causes. It contributes to the existing knowledge of NSDHL-related disorders and emphasizes the potential benefits of exome sequencing in prenatal diagnosis.

Asset Subtitle

Presenting Author - Asha N. Talati, MD, MS; Co-Author - Edward Spence, MD; Co-Author - Neeta L. Vora, MD, FACMG; Co-Author - William H. Goodnight, MD, MS;

Meta Tag

Congenital Anomaly

Dysmorphology

Exome sequencing

Fetal Therapy

Genotype-Phenotype Correlations

Malformation

NextGen Sequencing

Phenotype

Sequencing

Ultrasound

Co-Author Edward Spence, MD

Co-Author Neeta L. Vora, MD, FACMG

Co-Author William H. Goodnight, MD, MS

Presenting Author Asha N. Talati, MD, MS

Keywords

pathogenic variant

NSDHL gene

Congenital High Airway Obstruction syndrome

CHAOS syndrome

echogenic lungs

EXIT procedure

ichthyosiform skin lesions

exome sequencing

pulmonary hypoplasia

genetic testing