Severe pharyngeal stenosis and laryngomalacia in an individual of HNRNPU-related neurodevelopmental disorder associated with a novel nonsense variant.

Congenital anomalies 2025 Jan-Dec

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Heterozygous loss-of-function variants in heterogeneous nuclear ribonucleoprotein U (HNRNPU) cause early-onset developmental and epileptic encephalopathy with multiple congenital anomalies. Limited clinical information is currently available on HNRNPU-related neurodevelopmental disorder. The patient was a 1-year-old Japanese girl with developmental delay, hypotonia, early-onset epilepsy, respiratory distress, and distinctive facial features, including ptosis, epicanthus, a prominent nasal bridge, a wide nasal floor, a cleft soft palate, and micrognathia. Respiratory distress was caused by pharyngeal stenosis and laryngomalacia, which gradually worsened, necessitating a scheduled tracheostomy at 1 year and 7 months of age. We performed whole-exome sequencing and identified a novel de novo nonsense variant in HNRNPU. We herein describe the first case of HNRNPU-related neurodevelopmental disorder with severe airway anomalies and a novel nonsense variant, thereby expanding the phenotypic spectrum. © 2025 Japanese Teratology Society.

Citation

Yusuke Sasaki, Hiroaki Murakami, Yukiko Kuroda, Yumi Enomoto, Takuya Naruto, Syunsuke Nagara, Toshinari Koyama, Kunihiro Matsunami, Tatsuya Sakashita, Hideo Kaneko, Kyoko Morimoto, Atsushi Imamura, Kenji Kurosawa. Severe pharyngeal stenosis and laryngomalacia in an individual of HNRNPU-related neurodevelopmental disorder associated with a novel nonsense variant. Congenital anomalies. 2025 Jan-Dec;65(1):e70006