ORPHA:666

Osteogenesis imperfecta

Synonyms: OI · Brittle bone disease · Glass bone disease · Lobstein disease

Type: Disease
Group: Disorder
Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Age of onset: All ages
Status: active

A rare, genetic, primary bone dysplasias characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures. The clinical severity is heterogeneous.

Names in Orphadata languages

12 of 12 languages

Lang	Name	Synonyms
en	Osteogenesis imperfecta	OI · Brittle bone disease · Glass bone disease · Lobstein disease
fr	Ostéogenèse imparfaite	Maladie de Lobstein · Maladie des os de verre · OI
de	Osteogenesis imperfecta	Glasknochenkrankheit · Lobstein-Krankheit · OI · Porak-Durante-Krankheit
es	Osteogénesis imperfecta	Enfermedad de Lobstein · Enfermedad de los huesos de cristal · OI
it	Osteogenesi imperfetta	Malattia delle ossa di vetro · Malattia delle ossa fragili · Malattia di Lobstein · OI
nl	Osteogenesis imperfecta	Brozebottenziekte · Glazenbottenziekte · OI · Ziekte van Lobstein
pt	Osteogenesis imperfecta	Doença de Lobstein · Doença dos ossos Brittle · Doença dos ossos de vidro · Doença dos ossos quebradiços · OI · Osteogénese imperfeita
pl	Wrodzona łamliwość kości	Choroba szklanych kości · Osteopsathyrosis · Choroba kruchych kości · Choroba Lobsteina · Choroba Poraka i Durante · OI
cs	Osteogenesis imperfecta	Lobsteinova nemoc · OI · Osteopsathyrosis · Porakova a Durantova nemoc · Nemoc křehkých kostí · Nemoc skleněných kostí
uk	Недосконалий остеогенез	Захворювання крихких кісток · Хвороба скляної кістки · Хвороба Лобштейна · OI
zh	成骨不全	Porak和Durante病
tr	Osteogenezis imperfekta	OI · Lobstein hastalığı · Osteopsatiroz · Cam kemik hastalığı · Kırılgan kemik hastalığı · Porak ve Durante hastalığı

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	166200	BTNT		validated
OMIM	166210	BTNT		validated
OMIM	166220	BTNT		validated
OMIM	166230	BTNT		validated
OMIM	259420	BTNT		validated
OMIM	259440	BTNT		validated
OMIM	301014	BTNT		validated
OMIM	610682	BTNT		validated
OMIM	610915	BTNT		validated
OMIM	610967	BTNT		validated
OMIM	610968	BTNT		validated
OMIM	613848	BTNT		validated
OMIM	613849	BTNT		validated
OMIM	613982	BTNT		validated
OMIM	614856	BTNT		validated
OMIM	615066	BTNT		validated
OMIM	615220	BTNT		validated
OMIM	616229	BTNT		validated
OMIM	616507	BTNT		validated
OMIM	619131	BTNT		validated
OMIM	619795	BTNT		validated
ICD-10	Q78.0	E	specific	validated
ICD-11	LD24.K0	E	specific	validated
MONDO	0019019	E		validated
MeSH	D010013	E		validated
UMLS	C0029434	E		validated
GARD	1017	E		validated
MedDRA	10031243	E		validated

E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.

Classification

Preferential parent (Orphanet linearisation):

ORPHA:93419Rare bone disease

Parents in the classifications (1):

ORPHA:93446Primary bone dysplasia with decreased bone density
rare developmental anomalies during embryogenesis; rare genetic diseases; rare bone diseases

Children (5):

Genes

0 direct · 36 via subtypes

Orphanet records no gene directly on this code.

Recorded by Orphanet on subtypes of this disorder:

Gene	Subtype	Association	Status	HGNC	Ensembl	OMIM	Locus	Name	Source of validation
MBTPS2	ORPHA:216796Osteogenesis imperfecta type 1	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:15455	ENSG00000012174	300294	Xp22.12	membrane bound transcription factor peptidase, site 2	27380894[PMID]
MESD	ORPHA:216804Osteogenesis imperfecta type 2	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:13520	ENSG00000117899	607783	15q25.1	mesoderm development LRP chaperone	33596325[PMID]_31564437[PMID]
TENT5A	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:18345	ENSG00000112773	611357	6q14.1	terminal nucleotidyltransferase 5A	29358272[PMID]
WNT1	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:12774	ENSG00000125084	164820	12q13.12	Wnt family member 1	23499310[PMID]_25046257[PMID]
WNT1	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:12774	ENSG00000125084	164820	12q13.12	Wnt family member 1	23434763[PMID]_25046257[PMID]
BMP1	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:1067	ENSG00000168487	112264	8p21.3	bone morphogenetic protein 1	22052668[PMID]
COL1A1	ORPHA:216796Osteogenesis imperfecta type 1	Disease-causing germline mutation(s) in	Assessed	HGNC:2197	ENSG00000108821	120150	17q21.33	collagen type I alpha 1 chain	21438135[PMID]_20301472[PMID]
COL1A1	ORPHA:216804Osteogenesis imperfecta type 2	Disease-causing germline mutation(s) in	Assessed	HGNC:2197	ENSG00000108821	120150	17q21.33	collagen type I alpha 1 chain	21438135[PMID]_20301472[PMID]
COL1A1	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:2197	ENSG00000108821	120150	17q21.33	collagen type I alpha 1 chain	21438135[PMID]_20301472[PMID]
COL1A1	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:2197	ENSG00000108821	120150	17q21.33	collagen type I alpha 1 chain	21438135[PMID]_20301472[PMID]
COL1A2	ORPHA:216796Osteogenesis imperfecta type 1	Disease-causing germline mutation(s) in	Assessed	HGNC:2198	ENSG00000164692	120160	7q21.3	collagen type I alpha 2 chain	21438135[PMID]_20301472[PMID]
COL1A2	ORPHA:216804Osteogenesis imperfecta type 2	Disease-causing germline mutation(s) in	Assessed	HGNC:2198	ENSG00000164692	120160	7q21.3	collagen type I alpha 2 chain	21438135[PMID]_20301472[PMID]
COL1A2	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:2198	ENSG00000164692	120160	7q21.3	collagen type I alpha 2 chain	21438135[PMID]_20301472[PMID]
COL1A2	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:2198	ENSG00000164692	120160	7q21.3	collagen type I alpha 2 chain	21438135[PMID]_20301472[PMID]
CREB3L1	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:18856	ENSG00000157613	616215	11p11.2	cAMP responsive element binding protein 3 like 1	24079343[PMID]
CRTAP	ORPHA:216804Osteogenesis imperfecta type 2	Disease-causing germline mutation(s) in	Assessed	HGNC:2379	ENSG00000170275	605497	3p22.3	cartilage associated protein	21438135[PMID]
CRTAP	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:2379	ENSG00000170275	605497	3p22.3	cartilage associated protein	21438135[PMID]
CRTAP	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:2379	ENSG00000170275	605497	3p22.3	cartilage associated protein	21438135[PMID]
FKBP10	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:18169	ENSG00000141756	607063	17q21.2	FKBP prolyl isomerase 10	21438135[PMID]_25046257[PMID]
FKBP10	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:18169	ENSG00000141756	607063	17q21.2	FKBP prolyl isomerase 10	21438135[PMID]_25046257[PMID]
IFITM5	ORPHA:216828Osteogenesis imperfecta type 5	Disease-causing germline mutation(s) in	Assessed	HGNC:16644	ENSG00000206013	614757	11p15.5	interferon induced transmembrane protein 5	22863190[PMID]_22863195[PMID]_25046257[PMID]
MBTPS2	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:15455	ENSG00000012174	300294	Xp22.12	membrane bound transcription factor peptidase, site 2	27380894[PMID]
MBTPS2	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:15455	ENSG00000012174	300294	Xp22.12	membrane bound transcription factor peptidase, site 2	27380894[PMID]
P3H1	ORPHA:216804Osteogenesis imperfecta type 2	Disease-causing germline mutation(s) in	Assessed	HGNC:19316	ENSG00000117385	610339	1p34.2	prolyl 3-hydroxylase 1	21438135[PMID]
P3H1	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:19316	ENSG00000117385	610339	1p34.2	prolyl 3-hydroxylase 1	21438135[PMID]
P4HB	ORPHA:216796Osteogenesis imperfecta type 1	Disease-causing germline mutation(s) in	Assessed	HGNC:8548	ENSG00000185624	176790	17q25.3	prolyl 4-hydroxylase subunit beta	30913006[PMID]_30948499[PMID]
PPIB	ORPHA:216804Osteogenesis imperfecta type 2	Disease-causing germline mutation(s) in	Assessed	HGNC:9255	ENSG00000166794	123841	15q22.31	peptidylprolyl isomerase B	21438135[PMID]
PPIB	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:9255	ENSG00000166794	123841	15q22.31	peptidylprolyl isomerase B	21438135[PMID]
PPIB	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:9255	ENSG00000166794	123841	15q22.31	peptidylprolyl isomerase B	21282188[PMID]
SEC24D	ORPHA:216796Osteogenesis imperfecta type 1	Disease-causing germline mutation(s) in	Assessed	HGNC:10706	ENSG00000150961	607186	4q26	SEC24 homolog D, COPII component	25683121[PMID]
SERPINF1	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:8824	ENSG00000132386	172860	17p13.3	serpin family F member 1	21353196[PMID]_25046257[PMID]
SERPINF1	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:8824	ENSG00000132386	172860	17p13.3	serpin family F member 1	25046257[PMID]
SERPINH1	ORPHA:216812Osteogenesis imperfecta type 3	Disease-causing germline mutation(s) in	Assessed	HGNC:1546	ENSG00000149257	600943	11q13.5	serpin family H member 1	21438135[PMID]
SP7	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:17321	ENSG00000170374	606633	12q13.13	Sp7 transcription factor	21438135[PMID]
SPARC	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:11219	ENSG00000113140	182120	5q33.1	secreted protein acidic and cysteine rich	26027498[PMID]
TMEM38B	ORPHA:216820Osteogenesis imperfecta type 4	Disease-causing germline mutation(s) in	Assessed	HGNC:25535	ENSG00000095209	611236	9q31.2	transmembrane protein 38B	23313006[PMID]_25046257[PMID]

Prevalence and incidence

7 records

Type	Class	Value	Area	Qualification	Validation	Source
Point prevalence	1-5 / 10 000	8.06 / 100 000	Worldwide	Value and class	Validated	31769437[PMID]_25944380[PMID]_24715559[PMID]
Prevalence at birth	1-9 / 100 000	6.4 / 100 000	France	Value and class	Validated	2785882[PMID]
Prevalence at birth	1-9 / 1 000 000	0.4 / 100 000	Latin America	Value and class	Validated	3746832[PMID]
Prevalence at birth	1-9 / 100 000	1.5 / 100 000	Ireland	Value and class	Validated	22375084[PMID]
Prevalence at birth	1-9 / 100 000	6.95 / 100 000	United States	Value and class	Validated	22461456[PMID]_24715559[PMID]
Prevalence at birth	1-9 / 100 000	7.4 / 100 000	Sweden	Value and class	Validated	25944380[PMID]
Point prevalence	1-9 / 1 000 000	0.375 / 100 000	China	Value and class	Validated	34103049[PMID]

Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.

HPO phenotypes

114 annotations · validated 2020-04-08

HPO	Term (as annotated by Orphanet)	Diagnostic
Very frequent (99-80%)
HP:0000944	Abnormal metaphysis morphology
HP:0000772	Abnormal rib morphology
HP:0011073	Abnormality of dental color
HP:0000682	Abnormality of dental enamel
HP:0002992	Abnormality of tibia morphology
HP:0000248	Brachycephaly
HP:0000670	Carious teeth
HP:0000444	Convex nasal ridge
HP:0004331	Decreased skull ossification
HP:0005019	Diaphyseal thickening
HP:0001288	Gait disturbance
HP:0000365	Hearing impairment
HP:0001511	Intrauterine growth retardation
HP:0000256	Macrocephaly
HP:0000347	Micrognathia
HP:0000410	Mixed hearing impairment
HP:0000768	Pectus carinatum
HP:0000269	Prominent occiput
HP:0000883	Thin ribs
Frequent (79-30%)
HP:0030680	Abnormal cardiovascular system morphology
HP:0003103	Abnormal cortical bone morphology
HP:0003312	Abnormal form of the vertebral bodies
HP:0002823	Abnormality of femur morphology
HP:0011314	Abnormality of long bone morphology
HP:0000164	Abnormality of the dentition
HP:0003272	Abnormality of the hip bone
HP:0000739	Anxiety
HP:0004586	Biconcave vertebral bodies
HP:0000592	Blue sclerae
HP:0002653	Bone pain
HP:0007957	Corneal opacity
HP:0000973	Cutis laxa
HP:0000689	Dental malocclusion
HP:0000703	Dentinogenesis imperfecta
HP:0004621	Enlarged vertebral pedicles
HP:0003546	Exercise intolerance
HP:0012378	Fatigue
HP:0002980	Femoral bowing
HP:0003084	Fractures of the long bones
HP:0002857	Genu valgum
HP:0000501	Glaucoma
HP:0002150	Hypercalciuria
HP:0000975	Hyperhidrosis
HP:0002659	Increased susceptibility to fractures
HP:0001382	Joint hypermobility
HP:0001382	Joint hypermobility
HP:0000239	Large fontanelles
HP:0002505	Loss of ambulation
HP:0006640	Multiple ribs fractures
HP:0000774	Narrow chest
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001730	Progressive hearing impairment
HP:0002757	Recurrent fractures
HP:0004349	Reduced bone mineral density
HP:0004322	Short stature
HP:0003100	Slender long bone
HP:0002953	Vertebral compression fracture
HP:0000505	Visual impairment
Occasional (29-5%)
HP:0004306	Abnormality of the endocardium
HP:0002829	Arthralgia
HP:0006487	Bowing of the long bones
HP:0000978	Bruising susceptibility
HP:0030267	Calcification of the interosseus membrane of the forearm
HP:0002019	Constipation
HP:0000684	Delayed eruption of teeth
HP:0003083	Dislocated radial head
HP:0002015	Dysphagia
HP:0001371	Flexion contracture
HP:0001510	Growth delay
HP:0030268	Hyperplastic callus formation
HP:0000023	Inguinal hernia
HP:0005214	Intestinal obstruction
HP:0002808	Kyphosis
HP:0002983	Micromelia
HP:0002011	Morphological central nervous system abnormality
HP:0000787	Nephrolithiasis
HP:0002758	Osteoarthritis
HP:0003401	Paresthesia
HP:0000767	Pectus excavatum
HP:0003179	Protrusio acetabuli
HP:0004482	Relative macrocephaly
HP:0002650	Scoliosis
HP:0001518	Small for gestational age
HP:0003474	Somatic sensory dysfunction
HP:0001873	Thrombocytopenia
HP:0000325	Triangular face
HP:0100661	Trigeminal neuralgia
HP:0001537	Umbilical hernia
HP:0002119	Ventriculomegaly
HP:0100761	Visceral angiomatosis
HP:0002645	Wormian bones
Very rare (<4-1%)
HP:0004942	Aortic aneurysm
HP:0002647	Aortic dissection
HP:0001659	Aortic regurgitation
HP:0002616	Aortic root aneurysm
HP:0005294	Arterial dissection
HP:0001251	Ataxia
HP:0012366	Basilar invagination
HP:0002512	Brain stem compression
HP:0001342	Cerebral hemorrhage
HP:0002947	Cervical kyphosis
HP:0006824	Cranial nerve paralysis
HP:0002315	Headache
HP:0000238	Hydrocephalus
HP:0001634	Mitral valve prolapse
HP:0002643	Neonatal respiratory distress
HP:0010953	Noncommunicating hydrocephalus
HP:0000639	Nystagmus
HP:0002089	Pulmonary hypoplasia
HP:0008905	Rhizomelia
HP:0003396	Syringomyelia
HP:0002273	Tetraparesis
HP:0005257	Thoracic hypoplasia

Run the differential on the 12 obligate / very frequent terms

Annotation source: 20301472[PMID]_25439022[PMID]_36905741[PMID]

Sources for this card

Orphanet page: orpha.net/en/disease/detail/666
This record as JSON: /data/d/666.json