AO1
MCID: ATL011
MIFTS: 36

Atelosteogenesis, Type I (AO1)

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

Aliases & Classifications for Atelosteogenesis, Type I

MalaCards integrated aliases for Atelosteogenesis, Type I:

Name: Atelosteogenesis, Type I 57 13 39
Giant Cell Chondrodysplasia 57 20 43 58 72
Atelosteogenesis Type 1 20 43 58 29 6
Aoi 57 20 43 58 72
Spondylohumerofemoral Hypoplasia 57 20 43 72
Atelosteogenesis Type I 73 43 58 72
Ao1 57 58 72
Spondylo-Humero-Femoral Dysplasia 58
Atelosteogenesis, Type 1 70
Atelosteogenesis 1 72

Characteristics:

Orphanet epidemiological data:

58
atelosteogenesis type i
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: infantile,stillbirth;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
de novo mutation
all cases have been stillborn or immediate neonatal death


HPO:

31
atelosteogenesis, type i:
Onset and clinical course neonatal death stillbirth
Inheritance autosomal dominant inheritance sporadic


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Atelosteogenesis, Type I

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1190 Definition A Pierre Robin syndrome associated with bone disease characterized by severe short-limbed dwarfism, joint dislocations, club feet along with distinctive facies and radiographic findings. Epidemiology Atelosteogenesis I (AOI) is a very rare infrequently described disorder. Clinical description Affected neonates are stillborn or die rapidly after birth and present clinically with severe short-limbed dwarfism, dislocated hip, knee and elbow joints, club feet and if born alive have cardiorespiratory failure. Craniofacial dysmorphism describes a prominent forehead, hypertelorism, a depressed nasal bridge with a grooved tip, micrognathia and frequently a cleft palate. There is a continuum with overlapping clinical findings between atelosteogenesis I, atelosteogenesis III and boomerang dysplasia. Etiology Atelosteogenesis I results from heterozygous mutations in exons 2-5 and 27-33 of the gene encoding filamin B ( FLNB ) located to 3p14. Diagnostic methods Diagnosis can be confirmed from skeletal radiographs, chondro-osseous histopathology and genetic testing. Distinctive radiographic findings comprise severe platyspondyly, distally tapered; shortened, incomplete or absent humeri and femurs; shortened or bowed radii, ulnas, and tibias; hypoplastic pelvis and fibulas; and deficient ossification of the metacarpals, middle and proximal phalanges. Differential diagnosis Differential diagnosis comprises other skeletal dysplasias with severe short-limbed dwarfism such as campomelic dysplasia, Ellis-van Creveld syndrome, achondroplasia, metatropic dysplasia, Roberts syndrome, short rib- polydactyly syndrome, and thanatophoric dysplasia. Other, differential diagnosis includes achondrogenesis, hypophosphatasia, and osteogenesis imperfecta. Antenatal diagnosis Prenatal ultrasound can detect bone dysplasia and other manifestation and plays an important role in early detection and diagnosis. Prenatal ultrasound findings for AOI may include severe limb shortening and deficient ossification of the long bones, shortened flaring or absent humeri and femurs from 18 weeks onwards. Other skeletal abnormalities as well as some facial dysmorphic features may be detectable. Genetic counseling All cases have been autosomal dominant and sporadic resulting from de novo mutations in FLNB. Management and treatment Palliative care is offered to newborns suffering from AOI. Prognosis Prognosis is poor. Death is often due to a combination of pulmonary hypoplasia and tracheobronchomalacia early in life.

MalaCards based summary : Atelosteogenesis, Type I, also known as giant cell chondrodysplasia, is related to infantile apnea and atelosteogenesis. An important gene associated with Atelosteogenesis, Type I is FLNB (Filamin B). Affiliated tissues include colon and bone, and related phenotypes are talipes equinovarus and brachydactyly

MedlinePlus Genetics : 43 Atelosteogenesis type 1 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. Characteristic facial features include a prominent forehead, wide-set eyes (hypertelorism), an upturned nose with a grooved tip, and a very small lower jaw and chin (micrognathia). Affected individuals may also have an opening in the roof of the mouth (a cleft palate). Males with this condition can have undescended testes.Individuals with atelosteogenesis type 1 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.

OMIM® : 57 Atelosteogenesis is the name given by Maroteaux et al. (1982) to a lethal chondrodysplasia characterized by distal hypoplasia of the humeri and femurs, hypoplasia of the midthoracic spine, occasionally complete lack of ossification of single hand bones, and the finding in cartilage of multiple degenerated chondrocytes encapsulated in fibrous tissue. Rimoin et al. (1980) termed it 'giant cell chondrodysplasia.' Patients with AO1 exhibit severe short-limbed dwarfism and dislocated elbows, hips, and knees (Jeon et al., 2014). (108720) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Atelosteogenesis 1: A lethal chondrodysplasia characterized by distal hypoplasia of the humeri and femurs, hypoplasia of the mid-thoracic spine, occasionally complete lack of ossification of single hand bones, and the finding in cartilage of multiple degenerated chondrocytes which are encapsulated in fibrous tissue.

Wikipedia : 73 Atelosteogenesis type I is a rare autosomal dominant condition. This condition is evident at birth and... more...

Related Diseases for Atelosteogenesis, Type I

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



Diseases related to Atelosteogenesis, Type I

Symptoms & Phenotypes for Atelosteogenesis, Type I

Human phenotypes related to Atelosteogenesis, Type I:

58 31 (show top 50) (show all 55)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 talipes equinovarus 58 31 frequent (33%) Frequent (79-30%) HP:0001762
2 brachydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001156
3 narrow chest 58 31 frequent (33%) Frequent (79-30%) HP:0000774
4 midface retrusion 58 31 frequent (33%) Frequent (79-30%) HP:0011800
5 pulmonary hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0002089
6 rhizomelia 58 31 frequent (33%) Frequent (79-30%) HP:0008905
7 abnormality of fibula morphology 58 31 frequent (33%) Frequent (79-30%) HP:0002991
8 coronal cleft vertebrae 58 31 frequent (33%) Frequent (79-30%) HP:0003417
9 short femur 58 31 frequent (33%) Frequent (79-30%) HP:0003097
10 abnormal ossification involving the femoral head and neck 58 31 frequent (33%) Frequent (79-30%) HP:0009107
11 absent or minimally ossified vertebral bodies 58 31 frequent (33%) Frequent (79-30%) HP:0004599
12 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
13 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
14 cleft palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000175
15 micrognathia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000347
16 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
17 polyhydramnios 58 31 occasional (7.5%) Occasional (29-5%) HP:0001561
18 platyspondyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000926
19 multiple renal cysts 58 31 occasional (7.5%) Occasional (29-5%) HP:0005562
20 proptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000520
21 joint dislocation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001373
22 telecanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000506
23 retinal dysplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0007973
24 enlarged cisterna magna 58 31 occasional (7.5%) Occasional (29-5%) HP:0002280
25 laryngotracheal stenosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0004894
26 neonatal short-trunk short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0008857
27 malrotation of colon 58 31 occasional (7.5%) Occasional (29-5%) HP:0004785
28 abnormal pancreatic duct morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0030992
29 laryngeal stenosis 58 31 Occasional (29-5%) HP:0001602
30 frontal bossing 31 HP:0002007
31 short neck 31 HP:0000470
32 depressed nasal bridge 31 HP:0005280
33 short nose 31 HP:0003196
34 cryptorchidism 31 HP:0000028
35 malar flattening 31 HP:0000272
36 elbow dislocation 31 HP:0003042
37 premature birth 31 HP:0001622
38 short metacarpal 31 HP:0010049
39 encephalocele 31 HP:0002084
40 fused cervical vertebrae 31 HP:0002949
41 fibular aplasia 31 HP:0002990
42 aplasia/hypoplasia of the ulna 31 HP:0006495
43 thoracic hypoplasia 58 Frequent (79-30%)
44 limb undergrowth 58 Frequent (79-30%)
45 11 pairs of ribs 31 HP:0000878
46 tibial bowing 31 HP:0002982
47 short long bone 58 Occasional (29-5%)
48 radial bowing 31 HP:0002986
49 short humerus 31 HP:0005792
50 short metatarsal 31 HP:0010743

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Face:
frontal bossing
micrognathia
midface hypoplasia

Head And Neck Nose:
depressed nasal bridge
hypoplastic nose

Genitourinary Internal Genitalia Male:
cryptorchidism

Skeletal Hands:
brachydactyly
short metacarpals
poor ossifications of metacarpal and proximal, middle phalanges
well-ossified distal phalanges

Skeletal Limbs:
elbow dislocation
rhizomelic limb shortening
short humeri with proximal clubbing and distal tapering
short, bowed radius
absent-hypoplastic ulnae
more
Skeletal Spine:
fused cervical vertebrae
thoracic platyspondyly
abnormal segmentation
coronal clefts
sagittal clefts

Respiratory Larynx:
laryngeal stenosis

Head And Neck Eyes:
prominent globes
edematous eyelids

Prenatal Manifestations Delivery:
stillborn
premature delivery

Head And Neck Neck:
short neck

Head And Neck Mouth:
cleft palate

Skeletal Feet:
talipes equinovarus
short metatarsals

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Neurologic Central Nervous System:
encephalocele

Chest Ribs Sternum Clavicles And Scapulae:
11 pairs of ribs

Growth Height:
short-limbed dwarfism

Chest External Features:
narrow thoracic cage

Laboratory Abnormalities:
giant cells (degenerating chondrocytes) in resting zone of epiphyseal cartilage

Clinical features from OMIM®:

108720 (Updated 05-Apr-2021)

Drugs & Therapeutics for Atelosteogenesis, Type I

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

Genetic Tests for Atelosteogenesis, Type I

Genetic tests related to Atelosteogenesis, Type I:

# Genetic test Affiliating Genes
1 Atelosteogenesis Type 1 29 FLNB

Anatomical Context for Atelosteogenesis, Type I

MalaCards organs/tissues related to Atelosteogenesis, Type I:

40
Colon, Bone

Publications for Atelosteogenesis, Type I

Articles related to Atelosteogenesis, Type I:

(show all 24)
# Title Authors PMID Year
1
Identification of a de novo heterozygous missense FLNB mutation in lethal atelosteogenesis type I by exome sequencing. 61 57 6
24624349 2014
2
Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. 57 6
14991055 2004
3
Two lethal chondrodysplasias with giant chondrocytes. 61 57
6614049 1983
4
"Giant cell" chondrodysplasia. 61 57
6614050 1983
5
Spondylohumerofemoral hypoplasia (giant cell chondrodysplasia): a neonatally lethal short-limbed skeletal displasia. 61 57
6753583 1982
6
Lethal bone dysplasia in a fetus with manifestations of atelosteogenesis I and Boomerang dysplasia. 57
8291529 1993
7
Atelosteogenesis I and boomerang dysplasia: a question of nosology. 57
1863996 1991
8
A case of atelosteogenesis. 57
2325095 1990
9
Atelosteogenesis: evidence for heterogeneity. 57
3562108 1987
10
de la Chapelle dysplasia. 57
3799721 1986
11
Atelosteogenesis. 57
7137218 1982
12
Neonatal osseous dysplasia I: 2nd report. 57
7163263 1982
13
New forms of neonatal death dwarfism. Report of 3 cases. 57
7194471 1981
14
Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome, Boomerang Dysplasia, and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach. 61
33255942 2020
15
Diagnosis of Atelosteogenesis Type I suggested by Fetal Ultrasonography and Atypical Paternal Phenotype with Mosaicism. 61
30231296 2018
16
Clinical report: Two patients with atelosteogenesis type I caused by missense mutations affecting the same FLNB residue. 61
23401428 2013
17
Atelosteogenesis type I: autopsy findings. 61
21985323 2011
18
Mutations in two regions of FLNB result in atelosteogenesis I and III. 61
16752402 2006
19
Occipital projections in the skeletal dysplasias. 61
15107965 2004
20
Prenatal diagnosis of atelosteogenesis type I at 21 weeks' gestation. 61
12454961 2002
21
Atypical skeletal changes in otopalatodigital syndrome type II: phenotypic overlap among otopalatodigital syndrome type II, boomerang dysplasia, atelosteogenesis type I and type III, and lethal male phenotype of Melnick-Needles syndrome. 61
9409862 1997
22
Atelosteogenesis syndromes: a review, with comments on their pathogenesis. 61
9133349 1997
23
Giant-cell chondrodysplasia in a male infant with clinical and radiological findings resembling the Piepkorn type of lethal osteochondrodysplasia. 61
9024569 1997
24
De la Chapelle dysplasia (atelosteogenesis type II): case report and review of the literature [corrected]. 61
7632220 1994

Variations for Atelosteogenesis, Type I

ClinVar genetic disease variations for Atelosteogenesis, Type I:

6 (show all 20)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FLNB NM_001457.4(FLNB):c.442T>A (p.Trp148Arg) SNV Pathogenic 21282 rs80356493 GRCh37: 3:58062922-58062922
GRCh38: 3:58077195-58077195
2 FLNB NM_001457.4(FLNB):c.4747_4749del (p.Asp1583del) Deletion Pathogenic 21284 rs80356498 GRCh37: 3:58121780-58121782
GRCh38: 3:58136053-58136055
3 FLNB NM_001457.4(FLNB):c.512T>A (p.Leu171Gln) SNV Pathogenic 38344 rs80356494 GRCh37: 3:58062992-58062992
GRCh38: 3:58077265-58077265
4 FLNB NM_001457.4(FLNB):c.542G>T (p.Gly181Val) SNV Pathogenic 21290 rs80356495 GRCh37: 3:58064444-58064444
GRCh38: 3:58078717-58078717
5 FLNB NM_001457.4(FLNB):c.549C>G (p.Cys183Trp) SNV Pathogenic 21291 rs80356496 GRCh37: 3:58064451-58064451
GRCh38: 3:58078724-58078724
6 FLNB NM_001457.4(FLNB):c.608A>C (p.Gln203Pro) SNV Pathogenic 21294 rs80356497 GRCh37: 3:58064510-58064510
GRCh38: 3:58078783-58078783
7 FLNB NM_001457.4(FLNB):c.604A>G (p.Met202Val) SNV Pathogenic 6401 rs121908895 GRCh37: 3:58064506-58064506
GRCh38: 3:58078779-58078779
8 FLNB NM_001457.4(FLNB):c.518C>T (p.Ala173Val) SNV Pathogenic 6400 rs121908894 GRCh37: 3:58062998-58062998
GRCh38: 3:58077271-58077271
9 FLNB NM_001457.4(FLNB):c.1006C>T (p.Gln336Ter) SNV Pathogenic 1031982 GRCh37: 3:58083563-58083563
GRCh38: 3:58097836-58097836
10 FLNB NM_001457.4(FLNB):c.3254del (p.Ile1085fs) Deletion Pathogenic 997590 GRCh37: 3:58108947-58108947
GRCh38: 3:58123220-58123220
11 FLNB NM_001457.4(FLNB):c.517G>A (p.Ala173Thr) SNV Pathogenic 126375 rs587777259 GRCh37: 3:58062997-58062997
GRCh38: 3:58077270-58077270
12 FLNB NM_001457.4(FLNB):c.5524T>C (p.Phe1842Leu) SNV Uncertain significance 1031983 GRCh37: 3:58131746-58131746
GRCh38: 3:58146019-58146019
13 FLNB NM_001457.4(FLNB):c.6643A>G (p.Ser2215Gly) SNV Uncertain significance 1031984 GRCh37: 3:58140526-58140526
GRCh38: 3:58154799-58154799
14 FLNB NM_001457.4(FLNB):c.906+3A>G SNV Uncertain significance 1030457 GRCh37: 3:58080684-58080684
GRCh38: 3:58094957-58094957
15 FLNB NM_001457.4(FLNB):c.4585T>C (p.Ser1529Pro) SNV Uncertain significance 1030456 GRCh37: 3:58120413-58120413
GRCh38: 3:58134686-58134686
16 FLNB NM_001457.4(FLNB):c.3616A>G (p.Met1206Val) SNV Uncertain significance 1030455 GRCh37: 3:58109309-58109309
GRCh38: 3:58123582-58123582
17 FLNB NM_001457.4(FLNB):c.776C>T (p.Ala259Val) SNV Uncertain significance 346301 rs376619286 GRCh37: 3:58067492-58067492
GRCh38: 3:58081765-58081765
18 FLNB NM_001457.4(FLNB):c.4391G>C (p.Gly1464Ala) SNV Uncertain significance 289425 rs886044175 GRCh37: 3:58118535-58118535
GRCh38: 3:58132808-58132808
19 FLNB NM_001457.4(FLNB):c.808A>G (p.Met270Val) SNV Uncertain significance 252548 rs145036794 GRCh37: 3:58080583-58080583
GRCh38: 3:58094856-58094856
20 MAP3K7 NM_145331.3(MAP3K7):c.1535C>T (p.Pro512Leu) SNV Uncertain significance 264698 rs886039230 GRCh37: 6:91228271-91228271
GRCh38: 6:90518552-90518552

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

72
# Symbol AA change Variation ID SNP ID
1 FLNB p.Ala173Val VAR_033072 rs121908894
2 FLNB p.Ser188Pro VAR_033073
3 FLNB p.Met202Val VAR_033074 rs121908895

Expression for Atelosteogenesis, Type I

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

Pathways for Atelosteogenesis, Type I

GO Terms for Atelosteogenesis, Type I

Sources for Atelosteogenesis, Type I

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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