Severe cleidocranial dysplasia and hypophosphatasia in a child with microdeletion of the C‐terminal region of RUNX2

• Published in: American journal of medical genetics. Part A Vol. 152A; no. 1; pp. 169 - 174
• Main Authors: El‐Gharbawy, Areeg H., Peeden, Joseph N., Lachman, Ralph S., Graham, John M., Moore, Stephen R., Rimoin, David L.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2010; Wiley-Liss
• Subjects: aCGH; Biological and medical sciences; Child; cleidocranial dysplasia; Cleidocranial Dysplasia - genetics; Core Binding Factor Alpha 1 Subunit - genetics; C‐terminus; Diseases of the osteoarticular system; Errors of metabolism; Humans; hypophosphatasia; Hypophosphatasia - genetics; kyphoscoliosis; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical genetics; Medical sciences; Metabolic diseases; microdeletion; Miscellaneous hereditary metabolic disorders; osteoporosis; Osteoporosis. Osteomalacia. Paget disease; RUNX2; Sequence Deletion; Alkaline phosphatase; Microdeletion; Deformation; Diseases of the osteoarticular system; Phosphoric monoester hydrolases; Esterases; Spine disease; Enzymopathy; aCGH; Osteoporosis; Osteochondrodysplasia; Child; Human; Enzyme; Metabolic diseases; Cleidocranial dysplasia; Hypophosphatasia; Terminal; C-terminus; RUNX2; Genetic disease; Kyphoscoliosis; Dorsal spine; Hydrolases; Severe
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.33146

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia due to mutations causing haploinsufficiency of RUNX2, an osteoblast transcription factor specific for bone and cartilage. The classic form of CCD is characterized by delayed closure of the fontanels, hypoplastic or aplastic clavicles and dental anomalies. Clinical reports suggest that a subset of patients with CCD have skeletal changes which mimic hypophosphatasia (HPP). Mutations in RUNX2 are detected in approximately 65% of cases of CCD, and microdeletions occur in 13%. We present clinical and radiological features in a 6‐year‐old child with severe CCD manifested by absence of the clavicles marked calvarial hypomineralization, osteoporosis and progressive kyphoscoliosis. HPP features included Bowdler spurs, severe osteopenia, and low alkaline phosphatase. Following negative mutation analysis of RUNX2, comparative genomic hybridization (CGH) microarray was performed. The result revealed a microdeletion in RUNX2, disrupting the C‐terminal part of the gene. © 2009 Wiley‐Liss, Inc.