HDAC8 - Related Cornelia de Lange Syndrome (CdLS5): An Atypical Neonatal Presentation

Dr. Somireddy Ramanjaneyulu Reddy, Dr. Bharadwaj Namala, Dr. Reena Lankala, Dr. Shreya Patlolla, Dr. Srinivas Tadaraj

Abstract: Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous cohesinopathy caused by variants in NIPBL, SMC1A, SMC3, RAD21, or HDAC8, with the HDAC8-related subtype (CdLS5) accounting for a small minority of cases and following X-linked dominant inheritance. We report a late-preterm, low-birth-weight female neonate who presented with a difficult perinatal transition, culture-negative sepsis, hypernatremia, neonatal seizures, hyperbilirubinemia, microcephaly, and ambiguous genitalia, initially raising suspicion of congenital adrenal hyperplasia (CAH). Endocrine work-up (testosterone, cortisol, DHEA-S, 17-hydroxyprogesterone and plasma renin activity) did not support classic CAH. Cranial MRI at follow-up showed a simplified gyral pattern with underopercularised sylvian fissures and prominent trigones, suggestive of a primary microcephaly syndrome. Whole exome sequencing subsequently identified a heterozygous nonsense variant in HDAC8 (NM_018486.3:c.490C>T, p.Arg164Ter), classified as pathogenic and previously reported in association with Cornelia de Lange syndrome 5, establishing the diagnosis. This case highlights the importance of considering cohesinopathies in the differential diagnosis of a neonate with primary microcephaly and atypical genitalia once classic CAH has been excluded, and demonstrates the diagnostic yield of exome sequencing in phenotypically atypical presentations of CdLS.

Keywords: Cornelia de Lange syndrome, HDAC8, cohesinopathy, primary microcephaly, ambiguous genitalia, neonatal seizures, whole exome sequencing

How to Cite?: Dr. Somireddy Ramanjaneyulu Reddy, Dr. Bharadwaj Namala, Dr. Reena Lankala, Dr. Shreya Patlolla, Dr. Srinivas Tadaraj, "HDAC8 - Related Cornelia de Lange Syndrome (CdLS5): An Atypical Neonatal Presentation", Volume 15 Issue 8, August 2026, International Journal of Science and Research (IJSR), Pages: 1216-1218, https://www.ijsr.net/getabstract.php?paperid=MR26818200747, DOI: https://dx.doi.org/10.21275/MR26818200747

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