AO3
MCID: ATL012
MIFTS: 33

Atelosteogenesis, Type Iii (AO3)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Atelosteogenesis, Type Iii

MalaCards integrated aliases for Atelosteogenesis, Type Iii:

Name: Atelosteogenesis, Type Iii 56 13
Atelosteogenesis Type 3 52 25 58 29 6 71
Aoiii 56 52 25 58 73
Ao3 56 52 58 73
Atelosteogenesis Type Iii 25 58 73
Atelosteogenesis 3 73

Characteristics:

Orphanet epidemiological data:

58
atelosteogenesis type iii
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
atelosteogenesis, type iii:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM 56 108721
OMIM Phenotypic Series 56 PS108720
MeSH 43 D010009
ICD10 via Orphanet 33 Q78.8
UMLS via Orphanet 72 C3668942
Orphanet 58 ORPHA56305
UMLS 71 C3668942

Summaries for Atelosteogenesis, Type Iii

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 56305 Definition A rare skeletal dysplasia characterized by short limbs dysmorphic facies and diagnostic radiographic findings. Epidemiology The prevalence of AOIII is unknown. Less than 25 affected patients have been reported. Clinical description AOII, like AOI, is characterized by rhizomelic limb shortness, dislocated hip, knee and elbow joints, broad hands and feet with broad digits, club feet, facial dysmorphism (midface hypoplasia, micrognathia , cleft palate ). Feeding problems and cardiorespiratory insufficiency are often seen in newborns. Clinical manifestations due to secondary complications past early infancy include learning and language problems and a gross motor developmental delay . Etiology Atelosteogenesis III results from missense mutations or small in-frame deletions in the FLNB gene reported in exons 2-5, 13 and 27-33 resulting in the translation of filamin B protein with altered biochemical properties. Diagnostic methods The diagnosis is established after a full skeletal x-ray survey and confirmed with genetic testing . AOIII demonstrates less delay of normal ossification compared to AOI. Antenatal diagnosis Prenatal diagnosis is possible by ultrasound from 20 weeks onward and by prenatal genetic testing in case of family history . Genetic counseling Most cases of AOIII are sporadic, but AOIII may be transmitted in an autosomal dominant manner. Affected individuals of which one of the parents presents with a milder phenotype (like Larsen syndrome ) (see this term) have been reported. This is likely to be related to a somatic mosaicism in the parents for a mutation that is germline in the offspring. Visit the Orphanet disease page for more resources.

MalaCards based summary : Atelosteogenesis, Type Iii, also known as atelosteogenesis type 3, is related to boomerang dysplasia and atelosteogenesis. An important gene associated with Atelosteogenesis, Type Iii is FLNB (Filamin B). Affiliated tissues include bone, eye and brain, and related phenotypes are respiratory insufficiency and talipes equinovarus

Genetics Home Reference : 25 Atelosteogenesis type 3 is a disorder that affects the development of bones throughout the body. Affected individuals are born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. Bones in the spine, rib cage, pelvis, and limbs may be underdeveloped or in some cases absent. As a result of the limb bone abnormalities, individuals with this condition have very short arms and legs. Their hands and feet are wide, with broad fingers and toes that may be permanently bent (camptodactyly) or fused together (syndactyly). Characteristic facial features include a broad forehead, wide-set eyes (hypertelorism), and an underdeveloped nose. About half of affected individuals have an opening in the roof of the mouth (a cleft palate.) Individuals with atelosteogenesis type 3 typically have an underdeveloped rib cage that affects the development and functioning of the lungs. As a result, affected individuals are usually stillborn or die shortly after birth from respiratory failure. Some affected individuals survive longer, usually with intensive medical support. They typically experience further respiratory problems as a result of weakness of the airways that can lead to partial closing, short pauses in breathing (apnea), or frequent infections. People with atelosteogenesis type 3 who survive past the newborn period may have learning disabilities and delayed language skills, which are probably caused by low levels of oxygen in the brain due to respiratory problems. As a result of their orthopedic abnormalities, they also have delayed development of motor skills such as standing and walking.

OMIM : 56 Atelosteogenesis type III (AO3) is an autosomal dominant skeletal dysplasia with vertebral abnormalities, disharmonious skeletal maturation, poorly modeled long bones, and joint dislocations. Craniofacial abnormalities, vertebral fusions, and carpal, tarsal, and phalangeal abnormalities are present (Krakow et al., 2004). There is considerable phenotypic overlap with AO1 (108720), but patients with AO3 have less delay in normal ossification, with better ossification of vertebrae, fibulae, metacarpals, and phalanges. Infants with AO3 often have respiratory and feeding difficulties, and respiratory complications and cervical spine instability are the apparent causes of death in reported cases (summary by Schultz et al., 1999). (108721)

UniProtKB/Swiss-Prot : 73 Atelosteogenesis 3: A short-limb lethal skeletal dysplasia with vertebral abnormalities, disharmonious skeletal maturation, poorly modeled long bones and joint dislocations. Recurrent respiratory insufficiency and/or infections usually result in early death.

Related Diseases for Atelosteogenesis, Type Iii

Diseases in the Atelosteogenesis family:

Atelosteogenesis, Type I Atelosteogenesis, Type Iii
Atelosteogenesis, Type Ii

Diseases related to Atelosteogenesis, Type Iii via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 boomerang dysplasia 11.4
2 atelosteogenesis 10.4
3 flnb-related disorders 10.2
4 dwarfism 10.2
5 larsen syndrome 10.1
6 odontochondrodysplasia 10.1
7 atelosteogenesis, type ii 10.1
8 otopalatodigital syndrome, type ii 10.1
9 alacrima, achalasia, and mental retardation syndrome 10.1
10 cleft palate, isolated 10.1
11 hypertelorism 10.1
12 scoliosis 10.1
13 tracheomalacia 10.1

Graphical network of the top 20 diseases related to Atelosteogenesis, Type Iii:



Diseases related to Atelosteogenesis, Type Iii

Symptoms & Phenotypes for Atelosteogenesis, Type Iii

Human phenotypes related to Atelosteogenesis, Type Iii:

58 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
2 talipes equinovarus 58 31 frequent (33%) Frequent (79-30%) HP:0001762
3 hip dislocation 58 31 frequent (33%) Frequent (79-30%) HP:0002827
4 patellar dislocation 58 31 frequent (33%) Frequent (79-30%) HP:0002999
5 elbow dislocation 58 31 frequent (33%) Frequent (79-30%) HP:0003042
6 vertebral hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0008417
7 knee dislocation 58 31 frequent (33%) Frequent (79-30%) HP:0004976
8 coronal cleft vertebrae 58 31 frequent (33%) Frequent (79-30%) HP:0003417
9 short tubular bones of the hand 58 31 frequent (33%) Frequent (79-30%) HP:0001248
10 distal tapering femur 58 31 frequent (33%) Frequent (79-30%) HP:0006408
11 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
12 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
13 micrognathia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000347
14 polyhydramnios 58 31 occasional (7.5%) Occasional (29-5%) HP:0001561
15 thoracic hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0005257
16 ulnar deviation of the wrist 58 31 occasional (7.5%) Occasional (29-5%) HP:0003049
17 hand clenching 58 31 occasional (7.5%) Occasional (29-5%) HP:0001188
18 fibular aplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002990
19 absent radius 58 31 occasional (7.5%) Occasional (29-5%) HP:0003974
20 laryngotracheomalacia 58 31 occasional (7.5%) Occasional (29-5%) HP:0008755
21 short tibia 58 31 occasional (7.5%) Occasional (29-5%) HP:0005736
22 thoracolumbar kyphosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0005619
23 absent humerus 58 31 occasional (7.5%) Occasional (29-5%) HP:0003862
24 epiphyseal stippling of the humerus 58 31 occasional (7.5%) Occasional (29-5%) HP:0003902
25 abnormal cervical curvature 58 31 occasional (7.5%) Occasional (29-5%) HP:0005905
26 club-shaped distal femur 58 31 occasional (7.5%) Occasional (29-5%) HP:0006384
27 malar flattening 31 HP:0000272
28 short neck 31 HP:0000470
29 frontal bossing 31 HP:0002007
30 scoliosis 31 HP:0002650
31 depressed nasal bridge 31 HP:0005280
32 midface retrusion 31 HP:0011800
33 cleft palate 31 HP:0000175
34 prominent occiput 31 HP:0000269
35 rhizomelia 31 HP:0008905
36 hypoplasia of the maxilla 31 HP:0000327
37 sandal gap 31 HP:0001852
38 flat acetabular roof 31 HP:0003180
39 tibial bowing 31 HP:0002982
40 abnormality of the humerus 58 Frequent (79-30%)
41 radial bowing 31 HP:0002986
42 cervical kyphosis 31 HP:0002947
43 hitchhiker thumb 31 HP:0001234
44 horizontal sacrum 31 HP:0003440
45 cervical segmentation defect 31 HP:0004632
46 tombstone-shaped proximal phalanges 31 HP:0006060
47 widened distal phalanges 31 HP:0006200

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Neck:
short neck

Skeletal Spine:
scoliosis
cervical kyphosis
cervical spine segmentation defects

Skeletal Skull:
prominent occiput
hypoplastic maxilla
hypoplastic mandible

Skeletal Limbs:
tibial bowing
radial bowing
rhizomelic shortening
elbow dislocations
club-shaped humeri with early proximal epiphyseal ossification
more
Skeletal Pelvis:
horizontal sacrum
rounded iliac bones with shortened sacrosciatic notches
vertical, block-like ischia
flat acetabular roofs

Head And Neck Face:
frontal bossing
micrognathia
midface hypoplasia

Head And Neck Mouth:
cleft palate

Skeletal Feet:
talipes equinovarus
hitchhiker halluces
widened gap first and second toe

Skeletal Hands:
hitchhiker thumb
tombstone-shaped proximal phalanges
widened distal phalanges
bifid digits

Head And Neck Nose:
flat nasal bridge

Clinical features from OMIM:

108721

Drugs & Therapeutics for Atelosteogenesis, Type Iii

Search Clinical Trials , NIH Clinical Center for Atelosteogenesis, Type Iii

Genetic Tests for Atelosteogenesis, Type Iii

Genetic tests related to Atelosteogenesis, Type Iii:

# Genetic test Affiliating Genes
1 Atelosteogenesis Type 3 29 FLNB

Anatomical Context for Atelosteogenesis, Type Iii

MalaCards organs/tissues related to Atelosteogenesis, Type Iii:

40
Bone, Eye, Brain, Lung, Testes

Publications for Atelosteogenesis, Type Iii

Articles related to Atelosteogenesis, Type Iii:

(show all 11)
# Title Authors PMID Year
1
Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. 56 6
14991055 2004
2
Atelosteogenesis type III: long term survival, prenatal diagnosis, and evidence for dominant transmission. 61 56
10076882 1999
3
Atelosteogenesis type III: a distinct skeletal dysplasia with features overlapping atelosteogenesis and oto-palato-digital syndrome type II. 61 56
2368807 1990
4
FLNB-Related Disorders 6
20301736 2008
5
Long-term survival of a pediatric patient affected with atelosteogenesis type 3 in an adult ICU. 61
29651828 2018
6
Atelosteogenesis type III: orthopedic management. 61
27258362 2017
7
Mutations in two regions of FLNB result in atelosteogenesis I and III. 61
16752402 2006
8
Fronto-otopalatodigital osteodysplasia: clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalatodigital syndrome types 1 and 2, and frontometaphyseal dysplasia. 61
10706363 2000
9
Atelosteogenesis syndromes: a review, with comments on their pathogenesis. 61
9133349 1997
10
Atelosteogenesis type III: a case report. 61
8008496 1994
11
Atelosteogenesis type 3: the first patient in Japan and a survivor for more than 1 year. 61
1442028 1992

Variations for Atelosteogenesis, Type Iii

ClinVar genetic disease variations for Atelosteogenesis, Type Iii:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FLNB NM_001457.4(FLNB):c.4804T>C (p.Ser1602Pro)SNV Pathogenic 21286 rs80356501 3:58121838-58121838 3:58136111-58136111
2 FLNB NM_001457.4(FLNB):c.4927G>T (p.Ala1643Ser)SNV Pathogenic 21288 rs80356502 3:58124074-58124074 3:58138347-58138347
3 FLNB NM_001457.4(FLNB):c.602C>T (p.Ala201Val)SNV Pathogenic 21293 rs80356499 3:58064504-58064504 3:58078777-58078777
4 FLNB NM_001457.4(FLNB):c.629G>T (p.Gly210Val)SNV Pathogenic 21295 rs80356500 3:58064531-58064531 3:58078804-58078804
5 FLNB NM_001457.4(FLNB):c.604A>G (p.Met202Val)SNV Pathogenic 6401 rs121908895 3:58064506-58064506 3:58078779-58078779
6 FLNB NM_001457.4(FLNB):c.2251G>C (p.Gly751Arg)SNV Likely pathogenic 6402 rs28937587 3:58095354-58095354 3:58109627-58109627
7 FLNB NM_001457.4(FLNB):c.808A>G (p.Met270Val)SNV Uncertain significance 252548 rs145036794 3:58080583-58080583 3:58094856-58094856
8 FLNB NM_001457.4(FLNB):c.4391G>C (p.Gly1464Ala)SNV Uncertain significance 289425 rs886044175 3:58118535-58118535 3:58132808-58132808

UniProtKB/Swiss-Prot genetic disease variations for Atelosteogenesis, Type Iii:

73
# Symbol AA change Variation ID SNP ID
1 FLNB p.Met202Val VAR_033074 rs121908895
2 FLNB p.Gly751Arg VAR_033080 rs28937587

Expression for Atelosteogenesis, Type Iii

Search GEO for disease gene expression data for Atelosteogenesis, Type Iii.

Pathways for Atelosteogenesis, Type Iii

GO Terms for Atelosteogenesis, Type Iii

Sources for Atelosteogenesis, Type Iii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....