SEMDHL
MCID: SPN438
MIFTS: 32

Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy (SEMDHL)

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

Aliases & Classifications for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

MalaCards integrated aliases for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy:

Name: Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy 57 72 29 6
Leukoencephalopathy-Metaphyseal Chondrodysplasia Syndrome 20 58
Leukoencephalopathy with Metaphyseal Chondrodysplasia 57 70
Semdhl 57 72
H-Smd 20 58
Leukoencephalopathy with Metaphyseal Chondrodysplasia; Lkmcd; Spondyloepimetaphyseal Dysplasia, X-Linked, with Mental Deterioration 57
X-Linked Spondyloepimetaphyseal Dysplasia with Hypomyelinating Leukodystrophy 20
Leukoencephalopathy-Spondyloepimetaphyseal Dysplasia Syndrome 58
Leukoencephalopathy-Spondylometaphyseal Dysplasia Syndrome 20
Hypomyelination-Spondyloepimetaphyseal Dysplasia Syndrome 58
Hypomyelination-Spondylometaphyseal Dysplasia Syndrome 20
Semd, X-Linked, with Mental Deterioration 57
Leukoencephalopathy-Semd Syndrome 58
Lkmcd 57

Characteristics:

Orphanet epidemiological data:

58
leukoencephalopathy-spondyloepimetaphyseal dysplasia syndrome
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
slowly progressive
onset in early childhood
normal development in first 6-12 months
death from respiratory failure often occurs

Inheritance:
x-linked recessive


HPO:

31
spondyloepimetaphyseal dysplasia, x-linked, with hypomyelinating leukodystrophy:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 83629 Definition A rare genetic neurological disorder characterized by the association of hypomyelinating leukodystrophy with spondylometaphyseal dysplasia. Patients present in infancy with absent or delayed ability to walk independently, slowly progressive motor deterioration, spasticity, ataxia, proximal weakness, and joint contractures. Additional manifestations include mild cognitive impairment, short stature, scoliosis, enlarged and deformed joints, dysarthria, nystagmus, visual defects, and mildly dysmorphic features, among others. Mode of inheritance is X-linked recessive.

MalaCards based summary : Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy, also known as leukoencephalopathy-metaphyseal chondrodysplasia syndrome, is related to hypomyelinating leukodystrophy and leukodystrophy, and has symptoms including fine tremor and unspecified visual loss. An important gene associated with Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy is AIFM1 (Apoptosis Inducing Factor Mitochondria Associated 1). Affiliated tissues include bone, and related phenotypes are leukoencephalopathy and metaphyseal chondrodysplasia

OMIM® : 57 X-linked spondyloepimetaphyseal dysplasia with hypomyelinating leukodystrophy (SEMDHL) is an X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy (summary by Miyake et al., 2017). (300232) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy: An X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy.

Related Diseases for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

Graphical network of the top 20 diseases related to Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy:



Diseases related to Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy

Symptoms & Phenotypes for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

Human phenotypes related to Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy:

58 31 (show top 50) (show all 62)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 leukoencephalopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002352
2 metaphyseal chondrodysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0005871
3 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
4 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
5 tremor 58 31 frequent (33%) Frequent (79-30%) HP:0001337
6 visual impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000505
7 reduced bone mineral density 58 31 frequent (33%) Frequent (79-30%) HP:0004349
8 toe walking 58 31 frequent (33%) Frequent (79-30%) HP:0040083
9 spastic paraplegia 58 31 frequent (33%) Frequent (79-30%) HP:0001258
10 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
11 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
12 cerebral atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002059
13 abnormality of the optic nerve 58 31 frequent (33%) Frequent (79-30%) HP:0000587
14 abnormal brainstem mri signal intensity 58 31 frequent (33%) Frequent (79-30%) HP:0012747
15 enlargement of the wrists 58 31 frequent (33%) Frequent (79-30%) HP:0003020
16 morphological abnormality of the pyramidal tract 58 31 frequent (33%) Frequent (79-30%) HP:0002062
17 large knee 58 31 frequent (33%) Frequent (79-30%) HP:0030866
18 abnormal astrocyte morphology 31 frequent (33%) HP:0100707
19 depressed nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0005280
20 anteverted nares 58 31 occasional (7.5%) Occasional (29-5%) HP:0000463
21 midface retrusion 58 31 occasional (7.5%) Occasional (29-5%) HP:0011800
22 horizontal nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000666
23 gait disturbance 58 Frequent (79-30%)
24 high palate 31 HP:0000218
25 short neck 31 HP:0000470
26 coarse facial features 31 HP:0000280
27 delayed skeletal maturation 31 HP:0002750
28 hypertelorism 31 HP:0000316
29 thick eyebrow 31 HP:0000574
30 short stature 31 HP:0004322
31 flexion contracture 31 HP:0001371
32 low-set ears 31 HP:0000369
33 intellectual disability, progressive 31 HP:0006887
34 brachydactyly 31 HP:0001156
35 platyspondyly 31 HP:0000926
36 low anterior hairline 31 HP:0000294
37 malar flattening 31 HP:0000272
38 wormian bones 31 HP:0002645
39 coxa vara 31 HP:0002812
40 short finger 31 HP:0009381
41 optic disc pallor 31 HP:0000543
42 broad foot 31 HP:0001769
43 broad palm 31 HP:0001169
44 hypoplasia of the odontoid process 31 HP:0003311
45 prominent sternum 31 HP:0000884
46 thin ribs 31 HP:0000883
47 broad nasal tip 31 HP:0000455
48 flared iliac wings 31 HP:0002869
49 flattened epiphysis 31 HP:0003071
50 anterior rib cupping 31 HP:0000907

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
hyperreflexia
ataxia
dysarthria
developmental regression
spastic paraplegia
more
Head And Neck Eyes:
nystagmus
hypertelorism
optic atrophy
loss of vision
pale optic discs
more
Skeletal:
osteopenia
enlarged joints
metaphyseal chondrodysplasia
spondyloepimetaphyseal dysplasia
delayed bone age
more
Head And Neck Nose:
depressed nasal bridge
anteverted nares
broad nasal tip

Growth Height:
short stature

Head And Neck Ears:
low-set ears
hearing impairment (in some patients)

Skeletal Feet:
brachydactyly
large, broad feet

Skeletal Pelvis:
coxa vara
flared iliac wings
short, hypoplastic femoral necks
cone-shaped capital femoral epiphyses
flat acetabula
more
Head And Neck Face:
midface hypoplasia
low frontal hairline
coarse facies
long smooth philtrum

Head And Neck Mouth:
high-arched palate

Skeletal Spine:
scoliosis
platyspondyly
vertebral body abnormalities
odontoid hypoplasia
exaggerated thoracic kyphosis

Head And Neck Neck:
short neck

Respiratory:
respiratory insufficiency
tracheostomy
mechanical ventilation

Chest Ribs Sternum Clavicles And Scapulae:
pectus carinatum
narrow chest
prominent sternum
thin ribs
short ribs
more
Muscle Soft Tissue:
hypertonia
hypotonia
muscle atrophy

Skeletal Hands:
brachydactyly
clinodactyly
small hands
coned epiphyses
large, broad hands
more
Skeletal Skull:
wormian bones

Skeletal Limbs:
peg-like central prominence of distal tibial metaphyses
widened metaphyses
small flattened epiphyses (distal femora and proximal tibiae)
epiphyseal sclerosis
broad knees
more
Skin Nails Hair Hair:
low frontal hairline
prominent eyebrows

Growth Other:
poor overall growth

Clinical features from OMIM®:

300232 (Updated 05-Apr-2021)

UMLS symptoms related to Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy:


fine tremor; unspecified visual loss

Drugs & Therapeutics for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

Search Clinical Trials , NIH Clinical Center for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy

Genetic Tests for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

Genetic tests related to Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy:

# Genetic test Affiliating Genes
1 Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy 29 AIFM1

Anatomical Context for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

MalaCards organs/tissues related to Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy:

40
Bone

Publications for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

Articles related to Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy:

# Title Authors PMID Year
1
A new type of leukoencephalopathy with metaphyseal chondrodysplasia maps to Xq25-q27. 6 61 57
16924009 2006
2
X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1. 6 57
28842795 2017
3
Spondyloepimetaphyseal dysplasia with neurodegeneration associated with AIFM1 mutation - a novel phenotype of the mitochondrial disease. 57 6
27102849 2017
4
A case of cerebral hypomyelination with spondylo-epi-metaphyseal dysplasia. 57 6
23239615 2013
5
Spondylo-epimetaphyseal dysplasia: a new X-linked variant with mental retardation. 57 6
10486082 1999

Variations for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

ClinVar genetic disease variations for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RAB33A , AIFM1 NM_004208.4(AIFM1):c.710A>G (p.Asp237Gly) SNV Pathogenic 694665 rs1202786652 GRCh37: X:129274579-129274579
GRCh38: X:130140604-130140604
2 RAB33A , AIFM1 NM_004208.4(AIFM1):c.705G>C (p.Gln235His) SNV Pathogenic 694667 rs377527583 GRCh37: X:129274584-129274584
GRCh38: X:130140609-130140609
3 RAB33A , AIFM1 NM_004208.4(AIFM1):c.697-44T>G SNV Pathogenic 694668 rs1603225182 GRCh37: X:129274636-129274636
GRCh38: X:130140661-130140661
4 RAB33A , AIFM1 NM_004208.4(AIFM1):c.720C>T (p.Asp240=) SNV Pathogenic 598756 rs1569418673 GRCh37: X:129274569-129274569
GRCh38: X:130140594-130140594
5 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1646C>T (p.Ala549Val) SNV Likely pathogenic 373913 rs761953453 GRCh37: X:129264069-129264069
GRCh38: X:130130094-130130094
6 RAB33A , AIFM1 NM_004208.4(AIFM1):c.1770+12T>C SNV Uncertain significance 932022 GRCh37: X:129263933-129263933
GRCh38: X:130129958-130129958

UniProtKB/Swiss-Prot genetic disease variations for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy:

72
# Symbol AA change Variation ID SNP ID
1 AIFM1 p.Gln235His VAR_083739
2 AIFM1 p.Asp237Gly VAR_083740
3 AIFM1 p.Asp237Val VAR_083741

Expression for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

Search GEO for disease gene expression data for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating Leukodystrophy.

Pathways for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

GO Terms for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

Sources for Spondyloepimetaphyseal Dysplasia, X-Linked, with Hypomyelinating...

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11 DGIdb
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56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
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69 Tocris
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71 UMLS via Orphanet
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