Spondylo-Megaepiphyseal-Metaphyseal Dysplasia (SMMD)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases
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Aliases & Classifications for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

MalaCards integrated aliases for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia:

Name: Spondylo-Megaepiphyseal-Metaphyseal Dysplasia 57 58 73 28 12 5 38 71
Smmd 57 73



Autosomal recessive 58 57


<1/1000000 (Worldwide) 58

Age Of Onset:

Infancy,Neonatal 58


57 (Updated 08-Dec-2022)
mutations result in inactivation of nkx3-2


Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis

External Ids:

OMIM® 57 613330
MeSH 43 D001848
ICD10 via Orphanet 32 Q77.7
UMLS via Orphanet 72 C2750066
Orphanet 58 ORPHA228387
MedGen 40 C2750066
UMLS 71 C2750066

Summaries for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Orphanet: 58 Spondylo-megaepiphyseal-metaphyseal dysplasia is a rare, genetic primary bone displasia characterized by disproportionate short stature with short, stiff neck and trunk and relatively long limbs, fingers and toes (which may present flexion contractures), severe vertebral body ossification delay (with frequent kyknodysostosis), markedly enlarged round epiphyses of the long bones, absent ossification of pubic bones and multiple pseudoepiphyses of the short tubular bones in hands and feet. Neurological manifestations resulting from cervical spine instability may be observed.

MalaCards based summary: Spondylo-Megaepiphyseal-Metaphyseal Dysplasia, also known as smmd, is related to pyle disease and metaphyseal dysplasia. An important gene associated with Spondylo-Megaepiphyseal-Metaphyseal Dysplasia is NKX3-2 (NK3 Homeobox 2). Affiliated tissues include bone, and related phenotypes are macrocephaly and short neck

OMIM®: 57 Spondylo-megaepiphyseal-metaphyseal dysplasia is a rare autosomal recessive skeletal dysplasia characterized by disproportionate short stature with a short and stiff neck and trunk; relatively long limbs that may show flexion contractures of the distal joints; delayed and impaired ossification of the vertebral bodies and the presence of large epiphyseal ossification centers and wide growth plates in the long tubular bones; and numerous pseudoepiphyses of the short tubular bones in hands and feet (summary by Hellemans et al., 2009). (613330) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot: 73 A skeletal dysplasia characterized by disproportionate short stature with a short and stiff neck and trunk, relatively long limbs that may show flexion contractures of the distal joints, delayed and impaired ossification of the vertebral bodies, the presence of large epiphyseal ossification centers and wide growth plates in the long tubular bones, and numerous pseudoepiphyses of the short tubular bones in hands and feet.

Related Diseases for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Diseases related to Spondylo-Megaepiphyseal-Metaphyseal Dysplasia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 pyle disease 10.7
2 metaphyseal dysplasia 10.7
3 cleidocranial dysplasia 1 10.5
4 osteochondrodysplasia 10.5
5 right atrial isomerism 10.3
6 otospondylomegaepiphyseal dysplasia, autosomal recessive 10.3
7 duodenal atresia 10.3
8 scoliosis 10.3
9 respiratory failure 10.3
10 clubfoot 10.3
11 dysostosis 10.3
12 spasticity 10.3
13 overgrowth syndrome 10.3

Graphical network of the top 20 diseases related to Spondylo-Megaepiphyseal-Metaphyseal Dysplasia:

Diseases related to Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Symptoms & Phenotypes for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Human phenotypes related to Spondylo-Megaepiphyseal-Metaphyseal Dysplasia:

30 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 30 HP:0000256
2 short neck 30 HP:0000470
3 hypertelorism 30 HP:0000316
4 flexion contracture 30 HP:0001371
5 genu valgum 30 HP:0002857
6 disproportionate short-trunk short stature 30 HP:0003521
7 genu varum 30 HP:0002970
8 coxa vara 30 HP:0002812
9 abnormally ossified vertebrae 30 HP:0100569
10 protuberant abdomen 30 HP:0001538
11 metaphyseal dysplasia 30 HP:0100255
12 short ribs 30 HP:0000773
13 hypoplastic ilia 30 HP:0000946
14 metaphyseal irregularity 30 HP:0003025
15 enlarged epiphyses 30 HP:0010580
16 delayed pubic bone ossification 30 HP:0008788
17 abnormal epididymis morphology 30 HP:0009714
18 pseudoepiphyses of hand bones 30 HP:0004288

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Head And Neck Head:

Head And Neck Eyes:

Skeletal Limbs:
genu valgum
genu varum
irregular metaphyses
Chest Ribs Sternum Clavicles And Scapulae:
short ribs
ribs are widely separated from vertebral column

Skeletal Hands:
delayed carpal bone ossification
pseudoepiphyses in metacarpal bones

Skeletal Spine:
absent vertebral body ossification

Head And Neck Neck:
short neck
limited mobility

Growth Height:
short stature

Skeletal Pelvis:
coxa vara
hypoplastic ilia
delayed pubic bone ossification
widened triradiate cartilage
large capital femoral epiphyses

Skeletal Feet:

Abdomen External Features:
protuberant abdomen (secondary to skeletal dysplasia)

Clinical features from OMIM®:

613330 (Updated 08-Dec-2022)

Drugs & Therapeutics for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Search Clinical Trials, NIH Clinical Center for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Genetic Tests for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Genetic tests related to Spondylo-Megaepiphyseal-Metaphyseal Dysplasia:

# Genetic test Affiliating Genes
1 Spondylo-Megaepiphyseal-Metaphyseal Dysplasia 28 NKX3-2

Anatomical Context for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Organs/tissues related to Spondylo-Megaepiphyseal-Metaphyseal Dysplasia:

MalaCards : Bone

Publications for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Articles related to Spondylo-Megaepiphyseal-Metaphyseal Dysplasia:

# Title Authors PMID Year
A novel NKX3-2 mutation associated with perinatal lethal phenotype of spondylo-megaepiphyseal-metaphyseal dysplasia in a neonate. 62 57 5
29704686 2019
Homozygous inactivating mutations in the NKX3-2 gene result in spondylo-megaepiphyseal-metaphyseal dysplasia. 62 57 5
20004766 2009
Spondylo-megaepiphyseal-metaphyseal dysplasia: an unusual bone dysplasia. 62 57
13680008 2003
Spondylo-megaepiphyseal-metaphyseal dysplasia: a new bone dysplasia resembling cleidocranial dysplasia. 62 57
3925497 1985
Zebrafish model for spondylo-megaepiphyseal-metaphyseal dysplasia reveals post-embryonic roles of Nkx3.2 in the skeleton. 62
33462117 2021
Structure-Activity Relationship and Mode of Action of a Frog Secreted Antibacterial Peptide B1CTcu5 Using Synthetically and Modularly Modified or Deleted (SMMD) Peptides. 62
25997127 2015
The role of Nkx3.2 in chondrogenesis. 62
27158253 2014
Severe neurologic manifestations from cervical spine instability in spondylo-megaepiphyseal-metaphyseal dysplasia. 62
22791571 2012
Success factors for telehealth--a case study. 62
16388982 2006
A novel method of identifying genetic mutations using an electrochemical DNA array. 62
15498924 2004

Variations for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

ClinVar genetic disease variations for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia:

# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NKX3-2 NM_001189.4(NKX3-2):c.337dup (p.Ala113fs) DUP Pathogenic
7491 rs606231352 GRCh37: 4:13545701-13545702
GRCh38: 4:13544077-13544078
2 NKX3-2 NM_001189.4(NKX3-2):c.336_337delinsT (p.Ala113fs) INDEL Pathogenic
7492 rs606231353 GRCh37: 4:13545702-13545703
GRCh38: 4:13544078-13544079
3 NKX3-2 NM_001189.4(NKX3-2):c.104_110del (p.Ala35fs) MICROSAT Pathogenic
7493 rs606231354 GRCh37: 4:13545929-13545935
GRCh38: 4:13544305-13544311
4 NKX3-2 NM_001189.4(NKX3-2):c.507_508del (p.Gly171fs) DEL Pathogenic/Likely Pathogenic
522597 rs1560165127 GRCh37: 4:13544111-13544112
GRCh38: 4:13542487-13542488
5 NKX3-2 NM_001189.4(NKX3-2):c.295G>A (p.Glu99Lys) SNV Uncertain Significance
1031215 rs1718061894 GRCh37: 4:13545744-13545744
GRCh38: 4:13544120-13544120
6 NKX3-2 NM_001189.4(NKX3-2):c.247C>A (p.Arg83=) SNV Benign
193201 rs9684692 GRCh37: 4:13545792-13545792
GRCh38: 4:13544168-13544168

Expression for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Search GEO for disease gene expression data for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia.

Pathways for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

GO Terms for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

Sources for Spondylo-Megaepiphyseal-Metaphyseal Dysplasia

8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
27 GO
28 GTR
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
36 LifeMap
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
70 Tocris
72 UMLS via Orphanet
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