AO1
MCID: ATL011
MIFTS: 36

Atelosteogenesis, Type I (AO1)

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

Aliases & Classifications for Atelosteogenesis, Type I

MalaCards integrated aliases for Atelosteogenesis, Type I:

Name: Atelosteogenesis, Type I 57 13 40
Giant Cell Chondrodysplasia 57 53 25 59 75
Atelosteogenesis Type 1 53 25 59 29 6
Aoi 57 53 25 59 75
Spondylohumerofemoral Hypoplasia 57 53 25 75
Atelosteogenesis Type I 25 59 75
Ao1 57 59 75
Spondylo-Humero-Femoral Dysplasia 59
Atelosteogenesis, Type 1 73
Atelosteogenesis 1 75

Characteristics:

Orphanet epidemiological data:

59
atelosteogenesis type i
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: infantile,stillbirth;

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
atelosteogenesis, type i:
Mortality/Aging neonatal death stillbirth
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Atelosteogenesis, Type I

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1190Disease definitionAtelosteogenesis I is a perinatally lethal skeletal dysplasia characterized by severe short-limbed dwarfism, joint dislocations, club feet along with distinctive facies and radiographic findings.EpidemiologyAOI is a very rare infrequently described disorder.Clinical descriptionAffected 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 (see these terms).EtiologyAtelosteogenesis I results from heterozygousmutations 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 diagnosisDifferential 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 (see these terms).Antenatal diagnosisPrenatal 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 counselingAll cases have been autosomal dominant and sporadic resulting from de novo mutations in FLNB.Management and treatmentPalliative care is offered to newborns suffering from AOI.PrognosisPrognosis is poor. Death is often due to a combination of pulmonary hypoplasia and tracheobronchomalacia early in life.Visit the Orphanet disease page for more resources.

MalaCards based summary : Atelosteogenesis, Type I, also known as giant cell chondrodysplasia, is related to larsen syndrome and atelosteogenesis. An important gene associated with Atelosteogenesis, Type I is FLNB (Filamin B). The drugs Capsaicin and Fentanyl have been mentioned in the context of this disorder. Affiliated tissues include bone, testes and eye, and related phenotypes are malar flattening and short neck

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)

UniProtKB/Swiss-Prot : 75 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.

Genetics Home Reference : 25 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.

Related Diseases for Atelosteogenesis, Type I

Diseases in the Atelosteogenesis family:

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

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

# Related Disease Score Top Affiliating Genes
1 larsen syndrome 11.1
2 atelosteogenesis 10.2
3 type i 10.2
4 boomerang dysplasia 9.9
5 otopalatodigital syndrome, type ii 9.9
6 melnick-needles syndrome 9.9
7 osteochondrodysplasia 9.8

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



Diseases related to Atelosteogenesis, Type I

Symptoms & Phenotypes for Atelosteogenesis, Type I

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Neck:
short neck

Head And Neck Nose:
depressed nasal bridge
hypoplastic nose

GenitourinaryInternal GenitaliaMale:
cryptorchidism

Skeletal Limbs:
elbow dislocation
rhizomelic limb shortening
short humeri with proximal clubbing and distal tapering
short, bowed radius
absent-hypoplastic ulnae
more
Skeletal Feet:
talipes equinovarus
short metatarsals

Skeletal Spine:
fused cervical vertebrae
abnormal segmentation
thoracic platyspondyly
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 Face:
frontal bossing
micrognathia
midface hypoplasia

Head And Neck Mouth:
cleft palate

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

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

Human phenotypes related to Atelosteogenesis, Type I:

32 (show all 35)
# Description HPO Frequency HPO Source Accession
1 malar flattening 32 HP:0000272
2 short neck 32 HP:0000470
3 frontal bossing 32 HP:0002007
4 depressed nasal bridge 32 HP:0005280
5 short nose 32 HP:0003196
6 cleft palate 32 HP:0000175
7 micrognathia 32 HP:0000347
8 narrow chest 32 HP:0000774
9 cryptorchidism 32 HP:0000028
10 rhizomelia 32 HP:0008905
11 brachydactyly 32 HP:0001156
12 elbow dislocation 32 HP:0003042
13 polyhydramnios 32 HP:0001561
14 talipes equinovarus 32 HP:0001762
15 midface retrusion 32 HP:0011800
16 proptosis 32 HP:0000520
17 short metacarpal 32 HP:0010049
18 encephalocele 32 HP:0002084
19 premature birth 32 HP:0001622
20 fused cervical vertebrae 32 HP:0002949
21 fibular aplasia 32 HP:0002990
22 aplasia/hypoplasia of the ulna 32 HP:0006495
23 11 pairs of ribs 32 HP:0000878
24 tibial bowing 32 HP:0002982
25 radial bowing 32 HP:0002986
26 laryngeal stenosis 32 HP:0001602
27 short humerus 32 HP:0005792
28 short metatarsal 32 HP:0010743
29 coronal cleft vertebrae 32 HP:0003417
30 short femur 32 HP:0003097
31 clubbing 32 HP:0001217
32 thoracic platyspondyly 32 HP:0004592
33 club-shaped proximal femur 32 HP:0006406
34 distal tapering femur 32 HP:0006408
35 multinucleated giant chondrocytes in epiphyseal cartilage 32 HP:0030330

Drugs & Therapeutics for Atelosteogenesis, Type I

Drugs for Atelosteogenesis, Type I (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 18)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Capsaicin Approved Phase 4 404-86-4 1548943
2
Fentanyl Approved, Illicit, Investigational, Vet_approved Phase 4 437-38-7 3345
3
Ketamine Approved, Vet_approved Phase 4 6740-88-1 3821
4 Adjuvants, Anesthesia Phase 4
5 Analgesics Phase 4
6 Analgesics, Opioid Phase 4
7 Anesthetics Phase 4
8 Anesthetics, Dissociative Phase 4
9 Anesthetics, General Phase 4
10 Anesthetics, Intravenous Phase 4
11 Central Nervous System Depressants Phase 4
12 Excitatory Amino Acid Antagonists Phase 4
13 Excitatory Amino Acids Phase 4
14 Narcotics Phase 4
15 Neurotransmitter Agents Phase 4
16 Peripheral Nervous System Agents Phase 4,Not Applicable
17 Hops Approved, Nutraceutical Not Applicable
18 Autonomic Agents Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Sensory Examination and Pharmacological Modulation of Oral Hyperexcitability in Patients With Atypical Odontalgia and Matched Healthy Controls Completed NCT00115102 Phase 4 fentanyl;S-ketamine
2 ACUVUE® OASYS® 1-DAY vs DAILIES TOTAL1® Completed NCT02750813 Not Applicable
3 Clinical Evaluation of ACUVUE® OASYS® 1-Day and ACUVUE® OASYS® Completed NCT02696317 Not Applicable
4 Investigation of the Acute Cognitive, Mood and Autonomic Effects of Hops in Healthy Participants Completed NCT01376869 Not Applicable

Search 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:

41
Bone, Testes, Eye

Publications for Atelosteogenesis, Type I

Articles related to Atelosteogenesis, Type I:

# Title Authors Year
1
Identification of a de novo heterozygous missense FLNB mutation in lethal atelosteogenesis type I by exome sequencing. ( 24624349 )
2014
2
Clinical report: Two patients with atelosteogenesis type I caused by missense mutations affecting the same FLNB residue. ( 23401428 )
2013
3
Atelosteogenesis type I: autopsy findings. ( 21985323 )
2011
4
Prenatal diagnosis of atelosteogenesis type I at 21 weeks' gestation. ( 12454961 )
2002
5
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. ( 9409862 )
1997
6
Giant-cell chondrodysplasia in a male infant with clinical and radiological findings resembling the Piepkorn type of lethal osteochondrodysplasia. ( 9024569 )
1997
7
Spondylohumerofemoral hypoplasia (giant cell chondrodysplasia): a neonatally lethal short-limbed skeletal displasia. ( 6753583 )
1982

Variations for Atelosteogenesis, Type I

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

75
# 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

ClinVar genetic disease variations for Atelosteogenesis, Type I:

6
(show all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 FLNB NM_001457.3(FLNB): c.518C> T (p.Ala173Val) single nucleotide variant Pathogenic rs121908894 GRCh37 Chromosome 3, 58062998: 58062998
2 FLNB NM_001457.3(FLNB): c.518C> T (p.Ala173Val) single nucleotide variant Pathogenic rs121908894 GRCh38 Chromosome 3, 58077271: 58077271
3 FLNB NM_001457.3(FLNB): c.604A> G (p.Met202Val) single nucleotide variant Pathogenic rs121908895 GRCh37 Chromosome 3, 58064506: 58064506
4 FLNB NM_001457.3(FLNB): c.604A> G (p.Met202Val) single nucleotide variant Pathogenic rs121908895 GRCh38 Chromosome 3, 58078779: 58078779
5 FLNB NM_001457.3(FLNB): c.442T> A (p.Trp148Arg) single nucleotide variant Pathogenic rs80356493 GRCh37 Chromosome 3, 58062922: 58062922
6 FLNB NM_001457.3(FLNB): c.442T> A (p.Trp148Arg) single nucleotide variant Pathogenic rs80356493 GRCh38 Chromosome 3, 58077195: 58077195
7 FLNB NM_001457.3(FLNB): c.4747_4749delGAC (p.Asp1583del) deletion Pathogenic rs80356498 GRCh37 Chromosome 3, 58121781: 58121783
8 FLNB NM_001457.3(FLNB): c.4747_4749delGAC (p.Asp1583del) deletion Pathogenic rs80356498 GRCh38 Chromosome 3, 58136054: 58136056
9 FLNB NM_001457.3(FLNB): c.542G> T (p.Gly181Val) single nucleotide variant Pathogenic rs80356495 GRCh37 Chromosome 3, 58064444: 58064444
10 FLNB NM_001457.3(FLNB): c.542G> T (p.Gly181Val) single nucleotide variant Pathogenic rs80356495 GRCh38 Chromosome 3, 58078717: 58078717
11 FLNB NM_001457.3(FLNB): c.549C> G (p.Cys183Trp) single nucleotide variant Pathogenic rs80356496 GRCh37 Chromosome 3, 58064451: 58064451
12 FLNB NM_001457.3(FLNB): c.549C> G (p.Cys183Trp) single nucleotide variant Pathogenic rs80356496 GRCh38 Chromosome 3, 58078724: 58078724
13 FLNB NM_001457.3(FLNB): c.608A> C (p.Gln203Pro) single nucleotide variant Pathogenic rs80356497 GRCh37 Chromosome 3, 58064510: 58064510
14 FLNB NM_001457.3(FLNB): c.608A> C (p.Gln203Pro) single nucleotide variant Pathogenic rs80356497 GRCh38 Chromosome 3, 58078783: 58078783
15 FLNB NM_001457.3(FLNB): c.512T> A (p.Leu171Gln) single nucleotide variant Pathogenic rs80356494 GRCh37 Chromosome 3, 58062992: 58062992
16 FLNB NM_001457.3(FLNB): c.512T> A (p.Leu171Gln) single nucleotide variant Pathogenic rs80356494 GRCh38 Chromosome 3, 58077265: 58077265
17 FLNB NM_001457.3(FLNB): c.517G> A (p.Ala173Thr) single nucleotide variant Pathogenic rs587777259 GRCh37 Chromosome 3, 58062997: 58062997
18 FLNB NM_001457.3(FLNB): c.517G> A (p.Ala173Thr) single nucleotide variant Pathogenic rs587777259 GRCh38 Chromosome 3, 58077270: 58077270

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 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....