LAUSR

Rationale: Clinical and genetic management of patients with rare syndromes is often a difficult, confusing, and slow task. Patient concerns: Male child patient with a multisystemic disease showing congenital heart defects, facial dysmorphism, skeletal malformations, and eye anomalies. Diagnosis: The patient remained clinically undiagnosed until the genetic results were conclusive and allowed to associate its clinical features with the germline ABL1 mutations-associated syndrome. Interventions: We performed whole-exome sequencing to uncover the underlying genetic defect in this patient. Subsequently, family segregation of identified mutations was performed by Sanger sequencing in all available family members. Outcomes: The only detected variant compatible with the disease was a novel heterozygous nonframeshift de novo deletion in ABL1 (c.434_436del; p.Ser145del). The affected residue lays in a functional domain of the protein, it is highly conserved among distinct species, and its loss is predicted as pathogenic by in silico studies. Lessons: Our results reinforce the involvement of ABL1 in clinically undiagnosed cases with developmental defects and expand the clinical and genetic spectrum of the recently reported ABL1-associated syndrome. In this sense, we described the third germline ABL1 causative mutation and linked, for the first time, ocular anterior chamber anomalies to this pathology. Thus, we suggest that this disorder may be more heterogeneous than is currently believed and may be overlapping with other multisystemic diseases, hence genetic and clinical reassessment of this type of cases should be considered to ensure proper diagnosis.