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In Depth Tutorials and Information
OI types I-IV.
4
Table 2.1
lists clinical OI types with
their associated mutations. (This is also discussed in
Chapter 1 by Sillence and Lemande.)
OI type I included most of those with the
tarda/levis
group and was defined by dominant inheritance, aver-
age stature, the absence of significant skeletal deformity
and blue sclerae. OI type II, the
severe tarda
group, was
characterized by perinatal lethal clinical presentations
with severe limb shortening, marked diminution of cal-
varial thickness and death, usually from respiratory
insufficiency. This group was thought to be inherited in
an autosomal recessive fashion because of sib recurrence
to 1979, the classification of OI was based only on skele-
tal features. As discussed by Smith et al. in 1983, the then
accepted classification was based on the age at which
fractures occurred.
2
Individuals born with fractures were
considered to have
osteogenesis imperfecta congenita
, while
those with fractures that occurred later were termed
osteogenesis imperfecta tarda.
OI tarda was subdivided into
a
gravis
group if fractures occurred during the first year
and a
levis
group if they occurred thereafter.
3
In 1979, Sillence, Rimoin and Danks used clinical,
radiographic and genetic characteristics to distinguish
four groups of patients with OI, soon transformed into
TABLE 2.1
Current Classification of OI Types
This table presents current classification of OI phenotypes and the associated mutations. Please refer to online. Online Mendelian Inheritance in Man® (OMIM) for
recent (post-publication) additions to this classification. OI types I-IV refer to the original Sillence classification. OI types IX-XV, which are inherited in an autosomal
recessive pattern present considerable overlap in phenotype and may not be distinguished on clinical features at this time. The designation moderate to severe
phenotype may include short stature, scoliosis with bony deformities of the thorax and skeletal deformities in the extremities. There is evidence of healed fractures
of both the femora and humeri and osteopenia is significant. DI may or may not be present. Rhizomelia may occur with type II OI and in type VII OI.
OI Type
Phenotype
Inheritance
Genetic Analysis
I Mild, non-deforming
Short or normal stature , blue sclera, mild joint laxity,
no DI
AD
Null mutation due to premature stop
codon
COL1A1
: normal collagen but
½ normal amount
II Perinatal lethal
Beaded ribs broad or narrow long bones, thin
calvarium, Rhizomelia, severe pulmonary
insufficiency
AD
COL1A1
and
COL1A2
structural
alterations in type I collagen.
CRTAP, LEPRE1
, PPIB
AR++
III Severe, deforming
White or blue sclera, DI, short stature, severe scoliosis,
wheel chair dependent
New mutation, AD
Structural alteration in type I collagen:
COL1A1, COL1A2
CRTAP
,
LEPRE1, PPIB
AR++
IV Moderately
deforming
Moderate skeletal deformity, frequent use of aids to
ambulation, blue sclera early that tend to lighten with
age, scoliosis, DI
AD
COL1A1
and
COL1A2
mutations
V Mild to moderately
deforming
Variable phenotype, mild to severe, white sclera,
dislocation radial head, interosseous membrane
calcification, hyperplastic callus, no DI. The defining
feature of OI type V is the mesh type lamellation
pattern on bone histology
AD
IFITM5
VI Hyperosteoidosis
Moderate/severe, white/blue sclerae. Early onset
fractures, osteomalacia on bone biopsy
AR
SERPINF1
VII Moderately
deforming
First Nations Quebec families, recessive inheritance,
moderate to severe, rhizomelia, no DI
AR
CRTAP, LEPRE1
VIII Severe, lethal
South African black population, lethal or severe, bone
deformity
AR
CRTAP, LEPREI
IX
Moderate to severe phenotype
AR
PPIB
X
Moderate to severe phenotype
AR
SERPINH1
XI
Moderate to severe phenotype
AR
FBK10
XII
Moderate to severe phenotype
AR
SP7/Osterix
XIII
Moderate to severe phenotype
AR
BMP1
XIV
Moderate to severe phenotype
AR
TMEM38B
XV
Moderate to severe phenotype
AR
Wnt1
+
+
In this table mutations associated with recessive disease are listed with OI Type II and type III categories because of the phenotype overlap. AD: Autosomal dominant
inheritance; AR: Autosomal recessive inheritance; DI: Dentinogenesis imperfecta.
