Purpose or Case Report: Diffuse osteosclerosis in pediatric patients can present diagnostic challenges due to overlapping features with conditions such as osteopetrosis, dysosteosclerosis, and pyknodysostosis. A 1-year-old male infant, born to non-consanguineous parents presented with global developmental delays, motor and speech impairments, and distinct craniofacial abnormalities. Notable features included macrocephaly, midfacial hypoplasia, and the presence of wormian bones. Clinical examination noted prominent veins over the skull, marked sutural markings, and wide wrists. Laboratory tests indicated anisocytic hypochromic anemia. An MRI of the brain demonstrated asymmetric ventriculomegaly, with deposits identified in the right orbits. The patient's family history included a sibling who had a history of Type 1 diabetes mellitus and juvenile idiopathic arthritis, who passed away at the age of three.
Radiographic evaluation revealed diffuse osteosclerosis of the vertebrae and ribs, a “bone within bone” appearance in both ilia, and bilateral femora showed Erlenmeyer flask deformity. Additional findings included diphyseal sclerosis with focal segmental cortical thickening in both tibiae and patchy sclerosis observed in the metaphysis. Similar findings were seen in metacarpals.
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Results: Genetic evaluation revealed compound heterozygous mutations in the SLC29A3 gene, specifically c.1087C>T (p.Arg363Trp) and c.73C>T (p.Arg25Ter), confirming a likely pathogenic association with Histiocytosis-Lymphadenopathy Plus Syndrome. Additionally, a heterozygous variant in the NFIB gene (c.1443C>G, p.Asp481Glu) was identified. Of the four histiocytic disorders, Faisalabad histiocytosis (FHC) was the most probable subtypes owing to bony involvement.
Conclusions: This case underscores the importance of a thorough clinical, radiological, and genetic evaluation in pediatric patients presenting with osteosclerotic features. The findings support a diagnosis of Histiocytosis-Lymphadenopathy Plus Syndrome, highlighting the necessity for ongoing research into the genetic underpinnings of osteosclerotic conditions. Future studies may elucidate the relationship between these findings and associated clinical features, ultimately aiding in improved diagnosis and management of similar cases.