Table 4.

Hereditary Disorders in the Differential Diagnosis of Infantile and Childhood-Onset Hypophosphatasia

GeneDisorderMOIClinical Features / Comment
COL1A1
COL1A2 1 		Osteogenesis imperfect (OI) (See COL1A1/2 Osteogenesis Imperfecta.)ADOI w/deformation (typically type III in infancy or type IV later on) may resemble hypophosphatasia clinically.
DSPP Dentinogenesis imperfect (OMIM DSPP Clinical Synopsis)ADWhether part of OI or an isolated finding, dentinogenesis imperfecta is distinguishable from dental presentation of hypophosphatasia.
LIFR Stuve-Wiedemann syndrome (OMIM 601559)ARPresents w/temperature dysregulation, diminished reflexes, & contractures, but severe perinatal presentation shares several features w/hypophosphatasia: respiratory insufficiency, bowing of long bones, metaphyseal dysplasia, low bone density for age, & fracture predilection.
NOTCH2 Hadju-Cheney syndrome (OMIM 102500)ADCharacterized by failure to thrive, dysmorphic facial features, early tooth loss, genitourinary anomalies, osteopenia, pathologic fractures, wormian bones, failure of suture ossification, basilar impression, vertebral abnormalities, joint laxity, bowed fibulae, short distal digits, acroosteolysis, & hirsutism
P4HB
SEC24D 		Cole-Carpenter syndrome (OMIM PS112240)AD
AR		Characterized by bone deformities, multiple fractures, proptosis, shallow orbits, orbital craniosynostosis, frontal bossing, & hydrocephalus
RUNX2 Cleidocranial dysplasia spectrum disorder ADCharacterized by late closure of fontanels & cranial sutures, aplastic clavicles, delayed mineralization of the pubic rami, & delayed eruption of deciduous & permanent teeth. Skeletal dysplasia is distinguishable from hypophosphatasia on clinical exam & skeletal survey. Dental dysplasia does not result in early tooth loss, & enamel hypoplasia is readily distinguishable from odontohypophosphatasia.
1.

For additional genes associated with OI, see COL1A1/2 Osteogenesis Imperfecta, Table 5.

From: Hypophosphatasia

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