Table 3.

Disorders Characterized by Osteopetrosis in the Differential Diagnosis of Pycnodysostosis

Features of Differential
Disorder Overlapping
w/Pycnodysostosis		Gene(s)Differential DisorderMOIFeatures of DIfferential Disorder Not Observed in Pycnodysostosis
Osteosclerosis, diffuse & focal sclerosis of varying severity, modeling defects at metaphysis, osteomyelitis, pathologic fractures, tooth eruption defects CA2 Osteopetrosis w/renal tubular acidosis (OMIM 259730)ARBone marrow impairment is rare; cranial nerve compression, DD, intracranial calcification, renal tubular acidosis
CLCN7
SNX10
TCIRG1 		Osteopetrosis, severe neonatal or infantile forms (See CLCN7-Related Osteopetrosis.)ARCranial nerve compression (II, VII, VIII), extramedullary hematopoiesis, hydrocephalus, hypocalcemia, pancytopenia
CLCN7
PLEKHM1
TNFSF11 		Osteopetrosis, intermediate form 1 (See CLCN7-Related Osteopetrosis.)ARAnemia, extramedullary hematopoiesis, occasional optic nerve compression
CLCN7 Osteopetrosis, late-onset form type 2 ADModerate hematologic failure, cranial nerve compression
FERMT3 Osteopetrosis, moderate form w/defective leukocyte adhesion (OMIM 612840)ARDefective neutrophil adhesion to endothelial cells, hepatosplenomegaly, leukocytosis, mucosal bleeding
IKBKG Osteopetrosis w/ectodermal dysplasia & immune defect (OMIM 300291)XLAnhidrotic ectodermal dysplasia, immunodeficiency (→ overwhelming infection), lymphedema
OSTM1 Osteopetrosis, infantile form, w/nervous system involvement (OMIM 259720)ARCranial nerve compression (II, VII, VIII), extramedullary hematopoiesis, hydrocephalus, hypocalcemia, pancytopenia, primary neurodegeneration incl retinal atrophy
TNFRSF11A Osteopetrosis, infantile form, osteoclast-poor w/immunoglobulin deficiency (OMIM 612301)ARAnemia, hepatosplenomegaly, hypogammaglobulinemia, thrombocytopenia
Osteosclerosis, short stature, pathologic fractures CSF1R
TNFRSF11A
SLC29A3 		Dysosteosclerosis (OMIM 618476) 2ARBrain abnormalities, progressive neurologic deterioration (specific to CSF1R), patches of hyperpigmented skin, platyspondyly, radiolucency of widened submetaphyseal portions of tubular bones
Osteosclerosis localized mainly to metaphyses & epiphyseal margins of appendicular bones & metaphyseal equivalents of axial bones LRRK1 Osteosclerotic metaphyseal dysplasia 3ARDD; ↑ urinary pyridinoline & deoxypyridinoline excretion; ↑ serum alkaline phosphatase, aspartate aminotransferase & creatine kinase; seizures
Acroosteolysis, joint laxity, short stature, skull deformities NOTCH2 Hajdu-Cheney syndrome (OMIM 102500)ADMild ID (in a small proportion), osteoporosis
Clavicular dysplasia, delayed anterior fontanelle closure, delayed eruption of teeth, high arched palate, short stature RUNX2 Cleidocranial dysplasia spectrum disorder ADAbnormally shaped pelvic & pubic bones, absent clavicles, thoracic deformations

AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked

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From: Pycnodysostosis

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