Expanding the Genotypic and Phenotypic Spectrum of Li-Campeau Syndrome: A Homozygous Single-Exon Deletion in UBR7.

Biallelic pathogenic variants in UBR7, encoding ubiquitin protein ligase E3 component n-recognin 7, cause Li-Campeau syndrome (LICAS; OMIM #619189), which is characterized by developmental delay/intellectual disability, epilepsy, hypothyroidism, ptosis, genital anomalies, and cardiac anomalies. LICAS is an ultrarare disorder, and to date, only nine patients from eight unrelated families have been reported with detailed clinical phenotypes. Here, we report an 18-year-old female patient with dysmorphic facial features, ptosis, congenital hypothyroidism, intellectual disability, stereotypic hand movements, attention-deficit/hyperactivity disorder, hepatosplenomegaly, and toenail hypoplasia. In contrast to previously reported patients, all of whom presented with global developmental delay, our patient achieved age-appropriate early motor and language milestones, representing the mildest early developmental course reported in LICAS to date. Exome sequencing revealed a homozygous deletion encompassing Exon 7 of UBR7, representing the first single-exon deletion reported in this gene. This report expands both the phenotypic and genotypic spectrum of LICAS and underscores the clinical utility of Next generation sequencing-based copy-number variant analysis in the diagnostic workup of rare diseases.