MCID: GRC002
MIFTS: 25

Gracile Bone Dysplasia

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

Aliases & Classifications for Gracile Bone Dysplasia

MalaCards integrated aliases for Gracile Bone Dysplasia:

Name: Gracile Bone Dysplasia 57 53 59 75 29 6 40 73
Osteocraniosplenic Syndrome 57 53 59 75
Osteocraniostenosis 57 53 59 75
Habrodysplasia 57 53 75
Gcleb 57 75
Skeletal Dysplasia, Lethal, with Gracile Bones 57
Skeletal Dysplasia Lethal with Gracile Bones 53
Lethal Skeletal Dysplasia with Gracile Bones 75

Characteristics:

Orphanet epidemiological data:

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

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
death in utero or in early infancy is common


HPO:

32
gracile bone dysplasia:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Gracile Bone Dysplasia

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2763Disease definitionOsteocraniostenosis is a lethal skeletal dysplasia characterized by a cloverleaf skull anomaly, facial dysmorphism, limb shortness, splenic hypo/aplasia and radiological anomalies including thin tubular bones with flared metaphyses and deficient calvarial mineralization.EpidemiologyFirst described in 1989, less than 30 cases have been reported so far.Clinical description'This multiple congenital anomalies syndrome is characterized by dysmorphic features of the fetus and the newborn: the skull is misshapen, combining acrocephaly and cloverleaf deformity, fontanelles are very large; facial dysmorphism includes midface hypoplasia with telecanthus, short upturned nose, short philtrum, small inverted V-shaped mouth and low-set ears; limbs are also affected with bowed forearms, micromelia and acromicria with brachydactyly.'EtiologyEtiology of osteocraniostenosis is not well known, but some histological findings report growth plate disorganization and adjacent diaphyseal ossification. Recently, heterozygousmutations of the FAM111A gene, encoding a protein of unknown function and responsible of some autosomal dominant forms of Kenny-Caffey syndrome (see this term) with hypothyroidism and slender and dense bone, have been identified in patients with osteocraniostenosis. A clinical and genetic heterogeneity remains likely.Diagnostic methodsDiagnosis is based mainly on radiological and pathological examination. Radiological examination reveals hypomineralisation of the skull, flat and dense vertebral bodies, thin tubular bones with flared and dense metaphyses, brachymetacarpia and brachyphalangy with ''diabolo appearance'' (very thin tubular bones with abrupt metaphyseal flare) and lack of ossification of the distal phalanges. The spleen is hypoplasic or even absent. Diaphyseal fractures are frequent at birth.Differential diagnosisDifferential diagnosis includes the hypo/akinesia sequence, Hallermann-Streiff-FranÁois syndrome, Kenny-Caffey syndrome and other slender bone dysplasias, and some cases of osteogenesis imperfecta with slender bones (see these terms).Antenatal diagnosisPrenatal ultrasound observation reveals micromelic dwarfism, cranial deformity, mild intra-uterine growth retardation and sometimes fractures.Genetic counselingCases with FAM111A gene mutations show an autosomal dominant mode of inheritance with a majority of de novo mutations.Management and treatmentThere is no treatment for osteocraniostenosis.PrognosisPrognosis is very poor as most cases are stillborn or die in their first days of life.Visit the Orphanet disease page for more resources.

MalaCards based summary : Gracile Bone Dysplasia, is also known as osteocraniosplenic syndrome, and has symptoms including seizures An important gene associated with Gracile Bone Dysplasia is FAM111A (Family With Sequence Similarity 111 Member A). Affiliated tissues include bone and spleen, and related phenotypes are hydrocephalus and seizures

OMIM : 57 Gracile bone dysplasia is a perinatally lethal condition characterized by gracile bones with thin diaphyses, premature closure of basal cranial sutures, and microphthalmia (summary by Unger et al., 2013). (602361)

UniProtKB/Swiss-Prot : 75 Gracile bone dysplasia: A perinatally lethal condition characterized by narrowing of the medullary cavity of the long bones and of the skull, gracile bones with thin diaphyses, premature closure of basal cranial sutures, and microphthalmia. Most affected individuals who survive beyond the perinatal period develop hypocalcemia with low parathyroid hormone levels.

Related Diseases for Gracile Bone Dysplasia

Symptoms & Phenotypes for Gracile Bone Dysplasia

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
hydrocephalus
seizures
developmental delay

Head And Neck Face:
prominent forehead

Head And Neck Eyes:
microphthalmia
aniridia

Laboratory Abnormalities:
hypocalcemia

Head And Neck Mouth:
ankyloglossia

Growth Other:
failure to thrive, severe

Skeletal:
bones dense but thin
obliteration of medullary cavity seen on radiography

Skeletal Limbs:
micromelic short limbs
flared metaphyses
long bone fractures prenatally

Growth Height:
short stature

Abdomen:
ascites

Skeletal Hands:
brachydactyly

Genitourinary External Genitalia Male:
micropenis

AbdomenSpleen:
hypoplastic spleen
asplenia (rare)

Chest Ribs Sternum Clavicles And Scapulae:
thin ribs and clavicles

Skeletal Skull:
cloverleaf-shaped skull
hypoplastic cranial bones
decreased mineralization of skull (in some patients)


Clinical features from OMIM:

602361

Human phenotypes related to Gracile Bone Dysplasia:

32 (show all 18)
# Description HPO Frequency HPO Source Accession
1 hydrocephalus 32 HP:0000238
2 seizures 32 HP:0001250
3 failure to thrive 32 HP:0001508
4 global developmental delay 32 HP:0001263
5 short stature 32 HP:0004322
6 prominent forehead 32 HP:0011220
7 ascites 32 HP:0001541
8 microphthalmia 32 HP:0000568
9 brachydactyly 32 HP:0001156
10 hypocalcemia 32 HP:0002901
11 asplenia 32 occasional (7.5%) HP:0001746
12 micropenis 32 HP:0000054
13 decreased skull ossification 32 occasional (7.5%) HP:0004331
14 aniridia 32 HP:0000526
15 slender long bone 32 HP:0003100
16 ankyloglossia 32 HP:0010296
17 flared metaphysis 32 HP:0003015
18 hypoplastic spleen 32 HP:0006270

UMLS symptoms related to Gracile Bone Dysplasia:


seizures

Drugs & Therapeutics for Gracile Bone Dysplasia

Search Clinical Trials , NIH Clinical Center for Gracile Bone Dysplasia

Genetic Tests for Gracile Bone Dysplasia

Genetic tests related to Gracile Bone Dysplasia:

# Genetic test Affiliating Genes
1 Gracile Bone Dysplasia 29 FAM111A

Anatomical Context for Gracile Bone Dysplasia

MalaCards organs/tissues related to Gracile Bone Dysplasia:

41
Bone, Spleen

Publications for Gracile Bone Dysplasia

Articles related to Gracile Bone Dysplasia:

# Title Authors Year
1
Two familial cases with a lethal gracile bone dysplasia and intrauterine growth retardation. ( 12687665 )
2003
2
Gracile bone dysplasia. ( 9450865 )
1998

Variations for Gracile Bone Dysplasia

UniProtKB/Swiss-Prot genetic disease variations for Gracile Bone Dysplasia:

75
# Symbol AA change Variation ID SNP ID
1 FAM111A p.Thr338Ala VAR_069513 rs587777014
2 FAM111A p.Pro527Thr VAR_069516 rs587777015
3 FAM111A p.Asp528Gly VAR_069517 rs587777013

ClinVar genetic disease variations for Gracile Bone Dysplasia:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 FAM111A FAM111A, 3-BP DEL, 1026TTC deletion Pathogenic
2 FAM111A NM_001142519.2(FAM111A): c.1583A> G (p.Asp528Gly) single nucleotide variant Pathogenic/Likely pathogenic rs587777013 GRCh37 Chromosome 11, 58920724: 58920724
3 FAM111A NM_001142519.2(FAM111A): c.1583A> G (p.Asp528Gly) single nucleotide variant Pathogenic/Likely pathogenic rs587777013 GRCh38 Chromosome 11, 59153251: 59153251
4 FAM111A NM_001142519.2(FAM111A): c.1012A> G (p.Thr338Ala) single nucleotide variant Pathogenic/Likely pathogenic rs587777014 GRCh37 Chromosome 11, 58920153: 58920153
5 FAM111A NM_001142519.2(FAM111A): c.1012A> G (p.Thr338Ala) single nucleotide variant Pathogenic/Likely pathogenic rs587777014 GRCh38 Chromosome 11, 59152680: 59152680
6 FAM111A NM_001142519.2(FAM111A): c.1579C> A (p.Pro527Thr) single nucleotide variant Pathogenic/Likely pathogenic rs587777015 GRCh37 Chromosome 11, 58920720: 58920720
7 FAM111A NM_001142519.2(FAM111A): c.1579C> A (p.Pro527Thr) single nucleotide variant Pathogenic/Likely pathogenic rs587777015 GRCh38 Chromosome 11, 59153247: 59153247

Expression for Gracile Bone Dysplasia

Search GEO for disease gene expression data for Gracile Bone Dysplasia.

Pathways for Gracile Bone Dysplasia

GO Terms for Gracile Bone Dysplasia

Sources for Gracile Bone Dysplasia

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
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