KBG Syndrome Complicated with Chylothorax in A Newborn: A Case Report and Literature Review

Yuqian Wang¹Xin Peng¹Jing Zhu¹Ning Zou¹Xiaotong Yu²Liu Yang^1*

• ¹Second Affiliated Hospital of Dalian Medical University, Dalian, China
• ²Dalian Women and Children's Medical Center, Dalian, China

Abstract 17 Objective: To discuss a unique case of KBG syndrome (KBGS) in neonates that 18 developed congenital chylothorax and to examine how ANKRD11 gene variations 19 may be related to lymphatic malformation. 20 Methods: The newborn was delivered at 38+5 weeks of gestation, presenting with 21 congenital chylothorax, a ventricular septal defect, feeding difficulties, and 22 craniofacial dysmorphism, and has been diagnosed with KBGS. Whole exome 23 sequencing (WES) was employed to validate the diagnosis of a genetic disorder. 24 Also, a systematic literature search of published KBGS cases between 1975 and June 25 2025 (n = 246) was carried out. 26 Results: The newborn was found to have a heterozygous ANKRD11 frameshift 27 variant (NM_013275.6: c.37683769 del; p.His1256Glnfs *26) , which came from his 28 mother. The clinical presentation was congenital chylothorax, craniofacial 29 dysmorphism (triangular face, bulging forehead, hypertelorism, short nose root, 30 anteverted nostrils, big ears, and micrognathia), ventricular septal defect, and 31 difficulty feeding. This was found to be the second case of KBGS with chylothorax in 32 the literature review. The literature review revealed that the predominant universal 33 neonatal phenotypes were feeding challenges (52.1%) and small-for-gestational-age 34 status (41.1%). The long-term phenotypes included facial features (100%), 35 macrodontia of upper central incisors (93.9%), skeletal disorders (90.7%), and 36 developmental delay (93.2%). Other symptoms included short stature, neurological 37 problems, and visual and auditory impairment. The incidence of skeletal 38 3 developmental defects and developmental delay was considerably higher in truncated 39 variant patients compared to missense variant patients (p<0.05). 40 Conclusion: The newborn presented with KBGS complicated by chylothorax, 41 attributable to a pathogenic variant in the ANKRD11 gene. These results broaden the 42 existing knowledge of KBGS clinical and genetic spectra. WES or whole-genome 43 sequencing should be important in diagnosing patients with unexplained 44 developmental abnormalities. It is imperative that the management for KBGS is 45 multidisciplinary to deliver optimal prognosis and long-term outcomes.