Atypical presentation of Glass syndrome in a child with epilepsy, autism, and unusual bleeding and thermoregulation issues

We report a male child of Eastern European ancestry presenting with global developmental delay, absence of speech, autism spectrum disorder, and epilepsy confirmed by abnormal EEG recordings. Clinical evaluation revealed hypotonia, impaired fine and gross motor skills, anxiety, sleep disturbances, high pain threshold, and thermoregulation difficulties. Craniofacial features included a thin, elongated nose with a narrow nasal ridge and slightly downslanting palpebral fissures. Additional findings comprised prominent fetal pads, long fingers, selective agenesis of permanent upper central incisors, and recurrent severe epistaxis and oral cavity bleeding. Gastrointestinal symptoms included chronic constipation.
Whole-exome sequencing performed as a trio identified a heterozygous pathogenic de novo variant in SATB2 [NM_001172509.2:c.1166G>T p.(Arg389Leu)], consistent with Glass syndrome (GLASS) [MIM:612313]. The patient’s phenotype overlaps with the classical spectrum of GLASS, which includes intellectual disability, speech impairment, craniofacial dysmorphism, and dental anomalies. However, features such as recurrent oral bleeding, high pain threshold, and thermoregulation difficulties are rarely reported and may represent an expansion of the phenotypic variability associated with SATB2-related disorders.
This case emphasizes the importance of recognizing atypical features in SATB2-related syndromes and highlights the critical role of accurate clinical phenotyping combined with genetic testing for precise diagnosis and informed counseling.