Novel Variant in SOX5 Gene Pathogenic for Lamb–Shaffer Syndrome Co-existing with 7q35-7q36.3 Deletion in a Child with Developmental Delay: A Case Report from India

Abstract Background: Lamb–Shaffer syndrome (LAMSHF) is a rare neurodevelopmental disorder with dysmorphic features and skeletal abnormalities caused by a mutation in the SOX5 gene on chromosome 12p.12. Clinical Description: A 10-month-old female infant presented with fever and fast breathing, associated with global developmental delay and a history of recurrent hospitalizations for various infections. Earlier echocardiography records showed ventricular septal defect. On examination, the infant was in congestive cardiac failure along with features of severe malnutrition, microcephaly, dysmorphic facies, thoracic scoliosis, and a pan-systolic murmur. Management and Outcome: Routine blood investigations were normal, and chest X-ray showed hyperinflated lung fields. Whole-exome sequencing identified a novel likely pathogenic deletion in the SOX5 gene known to cause LAMSHF, as well as another likely pathogenic deletion, 7q35-7q36.3 deletion. The infant was managed along the lines of congestive heart failure, followed by occupational and physiotherapy. Conclusion: This report brings to light an unusual combination of a novel variant in the SOX5 gene causing LAMSHF syndrome associated with 7q35-7q36.3 deletion in an infant, probably the first reported from India.