MCID: ATL011
MIFTS: 37

Atelosteogenesis, Type I

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

Aliases & Classifications for Atelosteogenesis, Type I

MalaCards integrated aliases for Atelosteogenesis, Type I:

Name: Atelosteogenesis, Type I 53 13
Giant Cell Chondrodysplasia 53 49 24 55 71
Aoi 53 49 24 55 71
Spondylohumerofemoral Hypoplasia 53 49 24 71
Atelosteogenesis Type 1 49 24 55 28
Atelosteogenesis Type I 24 55 71
Ao1 53 55 71
Spondylo-Humero-Femoral Dysplasia 55
Atelosteogenesis, Type 1 69
Atelosteogenesis 1 71

Characteristics:

Orphanet epidemiological data:

55
atelosteogenesis type i
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: infantile,stillbirth;

OMIM:

53
Inheritance:
autosomal dominant

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


HPO:

31
atelosteogenesis, type i:
Mortality/Aging neonatal death stillbirth
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Atelosteogenesis, Type I

NIH Rare Diseases : 49 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. Last updated: 7/1/2013

MalaCards based summary : Atelosteogenesis, Type I, also known as giant cell chondrodysplasia, is related to atelosteogenesis and blood group, i system, and has symptoms including clubbing, malar flattening and short neck. An important gene associated with Atelosteogenesis, Type I is FLNB (Filamin B). The drugs Capsaicin and Ketamine have been mentioned in the context of this disorder. Affiliated tissues include bone, testes and eye.

OMIM : 53 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 : 71 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 : 24 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 atelosteogenesis 10.2
2 blood group, i system 9.9
3 boomerang dysplasia 9.9
4 otopalatodigital syndrome, type ii 9.9
5 melnick-needles syndrome 9.9
6 otopalatodigital 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:

53
Head And Neck Neck:
short neck

Head And Neck Nose:
depressed nasal bridge
hypoplastic nose

Genitourinary Internal Genitalia Male:
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 RibsSternum 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:

31 (show all 35)
# Description HPO Frequency HPO Source Accession
1 clubbing 31 HP:0001217
2 malar flattening 31 HP:0000272
3 short neck 31 HP:0000470
4 frontal bossing 31 HP:0002007
5 depressed nasal bridge 31 HP:0005280
6 short nose 31 HP:0003196
7 cleft palate 31 HP:0000175
8 micrognathia 31 HP:0000347
9 narrow chest 31 HP:0000774
10 cryptorchidism 31 HP:0000028
11 rhizomelia 31 HP:0008905
12 brachydactyly 31 HP:0001156
13 elbow dislocation 31 HP:0003042
14 polyhydramnios 31 HP:0001561
15 talipes equinovarus 31 HP:0001762
16 midface retrusion 31 HP:0011800
17 proptosis 31 HP:0000520
18 short metacarpal 31 HP:0010049
19 encephalocele 31 HP:0002084
20 premature birth 31 HP:0001622
21 fused cervical vertebrae 31 HP:0002949
22 fibular aplasia 31 HP:0002990
23 aplasia/hypoplasia of the ulna 31 HP:0006495
24 11 pairs of ribs 31 HP:0000878
25 tibial bowing 31 HP:0002982
26 radial bowing 31 HP:0002986
27 laryngeal stenosis 31 HP:0001602
28 short humerus 31 HP:0005792
29 short metatarsal 31 HP:0010743
30 coronal cleft vertebrae 31 HP:0003417
31 short femur 31 HP:0003097
32 thoracic platyspondyly 31 HP:0004592
33 club-shaped proximal femur 31 HP:0006406
34 distal tapering femur 31 HP:0006408
35 multinucleated giant chondrocytes in epiphyseal cartilage 31 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
Ketamine Approved, Vet_approved Phase 4 6740-88-1 3821
3
Fentanyl Approved, Illicit, Investigational, Vet_approved Phase 4 437-38-7 3345
4 Analgesics Phase 4
5 Central Nervous System Depressants Phase 4
6 Adjuvants, Anesthesia Phase 4
7 Narcotics Phase 4
8 Neurotransmitter Agents Phase 4
9 Analgesics, Opioid Phase 4
10 Anesthetics Phase 4
11 Anesthetics, Dissociative Phase 4
12 Anesthetics, General Phase 4
13 Anesthetics, Intravenous Phase 4
14 Peripheral Nervous System Agents Phase 4
15 Excitatory Amino Acid Antagonists Phase 4
16 Excitatory Amino Acids Phase 4
17 Hops Approved, Nutraceutical
18 Autonomic Agents

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
3 Clinical Evaluation of ACUVUE® OASYS® 1-Day and ACUVUE® OASYS® Completed NCT02696317
4 Investigation of the Acute Cognitive, Mood and Autonomic Effects of Hops in Healthy Participants Completed NCT01376869

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 28 FLNB

Anatomical Context for Atelosteogenesis, Type I

MalaCards organs/tissues related to Atelosteogenesis, Type I:

38
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
Giant-cell chondrodysplasia in a male infant with clinical and radiological findings resembling the Piepkorn type of lethal osteochondrodysplasia. ( 9024569 )
1997
6
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
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:

71
# 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
# Gene Variation Type Significance SNP ID Assembly Location
1 FLNB NM_001457.3(FLNB): c.442T> A (p.Trp148Arg) single nucleotide variant Pathogenic rs80356493 GRCh37 Chromosome 3, 58062922: 58062922
2 FLNB NM_001457.3(FLNB): c.4747_4749delGAC (p.Asp1583del) deletion Pathogenic rs80356498 GRCh37 Chromosome 3, 58121781: 58121783
3 FLNB NM_001457.3(FLNB): c.542G> T (p.Gly181Val) single nucleotide variant Pathogenic rs80356495 GRCh37 Chromosome 3, 58064444: 58064444
4 FLNB NM_001457.3(FLNB): c.549C> G (p.Cys183Trp) single nucleotide variant Pathogenic rs80356496 GRCh37 Chromosome 3, 58064451: 58064451
5 FLNB NM_001457.3(FLNB): c.608A> C (p.Gln203Pro) single nucleotide variant Pathogenic rs80356497 GRCh37 Chromosome 3, 58064510: 58064510
6 FLNB NM_001457.3(FLNB): c.512T> A (p.Leu171Gln) single nucleotide variant Pathogenic rs80356494 GRCh37 Chromosome 3, 58062992: 58062992
7 FLNB NM_001457.3(FLNB): c.517G> A (p.Ala173Thr) single nucleotide variant Pathogenic rs587777259 GRCh37 Chromosome 3, 58062997: 58062997
8 FLNB NM_001457.3(FLNB): c.518C> T (p.Ala173Val) single nucleotide variant Pathogenic rs121908894 GRCh37 Chromosome 3, 58062998: 58062998
9 FLNB NM_001457.3(FLNB): c.604A> G (p.Met202Val) single nucleotide variant Pathogenic rs121908895 GRCh37 Chromosome 3, 58064506: 58064506

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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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