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J Pediatr Genet 2014; 03(01): 029-034
DOI: 10.3233/PGE-14080
Case Report
Georg Thieme Verlag KG Stuttgart – New York

Osteogenesis imperfecta caused by PPIB mutation with severe phenotype and congenital hearing loss

Eric T. Rush
a   Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA
b   Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
d   Children's Hospital and Medical Center, Omaha, NE, USA
e   Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA
,
Kathleen S. Caldwell
e   Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA
,
Rose M. Kreikemeier
d   Children's Hospital and Medical Center, Omaha, NE, USA
,
Richard E. Lutz
a   Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA
d   Children's Hospital and Medical Center, Omaha, NE, USA
e   Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA
,
Paul W. Esposito
a   Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA
c   Department of Orthopedic Surgery, University of Nebraska Medical Center, Omaha, NE, USA
d   Children's Hospital and Medical Center, Omaha, NE, USA
› Author Affiliations
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Publication History

28 February 2014

26 May 2014

Publication Date:
27 July 2015 (online)

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Abstract

Osteogenesis imperfecta (OI) is an inherited disorder of connective tissue typically caused by defects in either COL1A1 or COL1A2. A number of other genes causative of this disorder have been found, including PPIB, which forms one subunit of the prolyl 3-hydroxylase enzyme complex. Patients with homozygous or compound heterozygous mutations in this gene have OI with a trend toward lethal or severe phenotype. We present a Native American female with prenatal diagnosis of OI. Long bones were shortened with significant rhizomelia. At birth, fractures were present in ribs, humerii, and femurs. She had significant respiratory disease at birth, and required oxygen throughout her life. She also had recurrent pneumonias, one of which ultimately caused her death at age 16 mo. She also had significant bilateral sensorineural hearing loss. Molecular testing showed that the patient was homozygous for a single nucleotide substitution in PPIB (c. 136-2A>G). Patients with OI caused by PPIB mutations have had variable disease, but with majority of either with perinatal lethality or progressively deforming severe disease. Patients with OI due to PPIB mutation have shown some differences in phenotype. There appears to be a trend toward rhizomelic shortening and less severe bowing of the extremities, as compared to patients with comparably severe OI caused by COL1A1 or COL1A2 mutation. Congenital hearing loss may be an inconsistent feature of this condition, or may have co-occurred in our patient for unrelated reasons. Still, patients with OI caused by PPIB mutation should have appropriate early and regular management of their hearing.

Keywords

Osteogenesis imperfecta - PPIB - skeletal dysplasia - metabolic bone disease - hearing loss - collagen diseases - brittle bone disease