LMHD
MCID: LNZ003
MIFTS: 44

Lenz-Majewski Hyperostotic Dwarfism (LMHD)

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

Aliases & Classifications for Lenz-Majewski Hyperostotic Dwarfism

MalaCards integrated aliases for Lenz-Majewski Hyperostotic Dwarfism:

Name: Lenz-Majewski Hyperostotic Dwarfism 57 12 74 58 73 15 39
Lenz-Majewski Syndrome 57 12 20 73 36 6
Lenz Majewski Hyperostotic Dwarfism 20 44 71
Lmhd 57 73
Multiple Congenital Anomalies, Mental Retardation and Progressive Skeletal Sclerosis 20
Hyperostotic Dwarfism Lenz-Majewski Type 20
Lenz-Majewski Hyperostotic Dysplasia 20
Lms 73

Characteristics:

Orphanet epidemiological data:

58
lenz-majewski hyperostotic dwarfism
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant

Miscellaneous:
all cases due to de novo mutation (last curated february 2014)


HPO:

31
lenz-majewski hyperostotic dwarfism:
Inheritance autosomal dominant inheritance sporadic


Classifications:

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


Summaries for Lenz-Majewski Hyperostotic Dwarfism

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2658DefinitionAn extremely rare syndrome associating dwarfism, characteristic facial appearance, cutis laxa and progressive bone sclerosis.EpidemiologyNine cases have been reported in the literature.Clinical descriptionMarked hypertelorism and broad forehead are noted in all patients as well as large ears. Loose and wrinkled atrophic skin with prominent veins is also apparent, giving the patient a progeroid appearance. Increasing generalized osteosclerosis of tubular bones, vertebrae and cranial bones is a characteristic feature. Cutaneous syndactyly of 2nd to 5th fingers was observed in all patients, as well as brachydactyly (see this term) and proximal symphalangism (see this term). All patients have moderate to severe intellectual deficit.Genetic counselingThe elevated age of some patient's fathers of the reported families is suggestive of an autosomal dominant de novo mutation.Visit the Orphanet disease page for more resources.

MalaCards based summary : Lenz-Majewski Hyperostotic Dwarfism, also known as lenz-majewski syndrome, is related to limb-mammary syndrome and lateral meningocele syndrome. An important gene associated with Lenz-Majewski Hyperostotic Dwarfism is PTDSS1 (Phosphatidylserine Synthase 1), and among its related pathways/superpathways are Glycerophospholipid metabolism and Metabolism. Affiliated tissues include bone, tongue and skin, and related phenotypes are macrocephaly and intellectual disability

Disease Ontology : 12 A syndrome characterized by intellectual disability, sclerosing bone dysplasia, distinct craniofacial, dental, cutaneous and distal-limb anomalies that has material basis in heterozygous mutation in PTDSS1 on chromosome 8q22.1.

OMIM® : 57 Lenz-Majewski hyperostotic dwarfism is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, distinct craniofacial and dental anomalies, loose skin, and distal limb anomalies, particularly brachydactyly and symphalangism. Patients have multiple radiographic abnormalities due to progressive generalized hyperostosis that affects the cranium, vertebrae, and diaphyses of tubular bones, leading to severe growth retardation (summary by Sousa et al., 2014). (151050) (Updated 05-Mar-2021)

KEGG : 36 Lenz-Majewski syndrome (LMS), also known as Lenz-Majewski hyperostotic dwarfism, is an extremely rare syndrome characterized by osteosclerosis, intellectual disability, characteristic facies, and distinct craniofacial, dental, cutaneous and distal-limb anomalies. Mutations in the PTDSS1 gene coding one of the phosphatidylserine (PS) synthase enzymes, PSS1, have been described as causative in LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS levels.

UniProtKB/Swiss-Prot : 73 Lenz-Majewski hyperostotic dwarfism: A syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. LMHD is characterized by the combination of sclerosing bone dysplasia, intellectual disability and distinct craniofacial, dental, cutaneous and distal limb anomalies. The progressive generalized hyperostosis associated with this syndrome affects the cranium, the vertebrae and the diaphyses of tubular bones, leading to severe growth restriction.

Wikipedia : 74 Lenz-Majewski syndrome (LMS), also known as Lenz-Majewski hyperostotic dwarfism (LMHD), is a skin... more...

Related Diseases for Lenz-Majewski Hyperostotic Dwarfism

Diseases related to Lenz-Majewski Hyperostotic Dwarfism via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 71)
# Related Disease Score Top Affiliating Genes
1 limb-mammary syndrome 11.6
2 lateral meningocele syndrome 11.5
3 scarf syndrome 11.5
4 laurence-moon syndrome 10.9
5 dwarfism 10.6
6 short-rib thoracic dysplasia 6 with or without polydactyly 10.6
7 dysostosis 10.5
8 leiomyosarcoma 10.4
9 hypertelorism 10.3
10 chromosome 2q35 duplication syndrome 10.3
11 peeling skin syndrome 1 10.3
12 brachydactyly 10.3
13 proximal symphalangism 10.3
14 bone disease 10.3
15 hyperostosis 10.3
16 cutis laxa 10.3
17 alacrima, achalasia, and mental retardation syndrome 10.3
18 hydrocephalus 10.3
19 body mass index quantitative trait locus 1 10.2
20 lacrimal duct defect 10.1
21 cryptorchidism, unilateral or bilateral 10.1
22 calvarial hyperostosis 10.1
23 choanal atresia, posterior 10.1
24 scoliosis 10.1
25 inguinal hernia 10.1
26 facial paralysis 10.1
27 communicating hydrocephalus 10.1
28 atp6v0a2-related cutis laxa 10.1
29 primary bone dysplasia with increased bone density 10.1
30 spastic paraplegia 55, autosomal recessive 10.0 DDHD1 CYP2U1
31 split-hand/foot malformation 1 10.0
32 isolated split hand-split foot malformation 10.0
33 spastic paraplegia 73, autosomal dominant 9.9 DDHD2 DDHD1
34 spastic paraplegia 46, autosomal recessive 9.9 DDHD2 CYP2U1
35 spastic paraplegia 48, autosomal recessive 9.9 DDHD2 CYP2U1
36 adult syndrome 9.8
37 cleft palate, isolated 9.8
38 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 9.8
39 insulin-like growth factor i 9.8
40 gastrointestinal stromal tumor 9.8
41 endometrial cancer 9.8
42 nail disorder, nonsyndromic congenital, 9 9.8
43 atrial fibrillation 9.8
44 sarcoma 9.8
45 anhidrosis 9.8
46 neutropenia 9.8
47 leiomyoma 9.8
48 thrombocytopenia 9.8
49 cerebral palsy 9.8
50 ectodermal dysplasia 9.8

Graphical network of the top 20 diseases related to Lenz-Majewski Hyperostotic Dwarfism:



Diseases related to Lenz-Majewski Hyperostotic Dwarfism

Symptoms & Phenotypes for Lenz-Majewski Hyperostotic Dwarfism

Human phenotypes related to Lenz-Majewski Hyperostotic Dwarfism:

58 31 (show top 50) (show all 95)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000256
2 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
3 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
4 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
5 hypertelorism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000316
6 macrotia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000400
7 mandibular prognathia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000303
8 thickened calvaria 58 31 hallmark (90%) Very frequent (99-80%) HP:0002684
9 abnormal cortical bone morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0003103
10 abnormality of the metaphysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000944
11 specific learning disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001328
12 prematurely aged appearance 58 31 hallmark (90%) Very frequent (99-80%) HP:0007495
13 aplasia/hypoplasia of the skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0008065
14 brachydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001156
15 choanal atresia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000453
16 abnormality of dental enamel 58 31 hallmark (90%) Very frequent (99-80%) HP:0000682
17 joint hyperflexibility 58 31 hallmark (90%) Very frequent (99-80%) HP:0005692
18 broad forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000337
19 redundant skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0001582
20 large fontanelles 58 31 hallmark (90%) Very frequent (99-80%) HP:0000239
21 finger syndactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0006101
22 symphalangism affecting the phalanges of the hand 58 31 hallmark (90%) Very frequent (99-80%) HP:0009773
23 delayed cranial suture closure 58 31 hallmark (90%) Very frequent (99-80%) HP:0000270
24 short palm 58 31 hallmark (90%) Very frequent (99-80%) HP:0004279
25 severe short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0003510
26 osteopetrosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0011002
27 facial hyperostosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0005465
28 aplastic clavicle 31 hallmark (90%) HP:0006660
29 facial palsy 58 31 frequent (33%) Frequent (79-30%) HP:0010628
30 inguinal hernia 58 31 frequent (33%) Frequent (79-30%) HP:0000023
31 thick vermilion border 58 31 frequent (33%) Frequent (79-30%) HP:0012471
32 cryptorchidism 58 31 frequent (33%) Frequent (79-30%) HP:0000028
33 wide mouth 58 31 frequent (33%) Frequent (79-30%) HP:0000154
34 hypospadias 58 31 frequent (33%) Frequent (79-30%) HP:0000047
35 abnormality of the metacarpal bones 58 31 frequent (33%) Frequent (79-30%) HP:0001163
36 epispadias 58 31 frequent (33%) Frequent (79-30%) HP:0000039
37 elbow ankylosis 58 31 frequent (33%) Frequent (79-30%) HP:0003070
38 femoral hernia 58 31 frequent (33%) Frequent (79-30%) HP:0100541
39 abnormal nasolacrimal system morphology 31 frequent (33%) HP:0000614
40 agenesis of corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0001274
41 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
42 kyphosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002808
43 hydrocephalus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000238
44 high, narrow palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0002705
45 hyperconvex fingernails 58 31 occasional (7.5%) Occasional (29-5%) HP:0001812
46 absent septum pellucidum 58 31 occasional (7.5%) Occasional (29-5%) HP:0001331
47 hypoplastic fingernail 58 31 occasional (7.5%) Occasional (29-5%) HP:0001804
48 bifid uvula 58 31 occasional (7.5%) Occasional (29-5%) HP:0000193
49 submucous cleft hard palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000176
50 hypogonadism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000135

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Growth Other:
failure to thrive
intrauterine growth retardation

Head And Neck Eyes:
hypertelorism
nasolacrimal duct stenosis

Skeletal Limbs:
diaphyseal thickening
knee flexion contracture
elbow flexion contractures
metaphyseal hypostosis
long, flared metaphyses
more
Head And Neck Face:
micrognathia
broad, prominent forehead

Abdomen Gastrointestinal:
anteriorly placed anus

Skeletal Hands:
proximal symphalangism
syndactyly
dorsiflexion of fingers
short/absent middle phalanges
hyperextensible digits

Skeletal Skull:
progressive sclerosis of skull base
shallow, distorted orbits
progressive sclerosis of facial bones

Head And Neck Head:
delayed closure of fontanel
disproportionately large head
large fontanels
microcephaly (in some patients)

Growth Height:
postnatal short stature

Head And Neck Mouth:
small tongue

Skin Nails Hair Hair:
sparse hair (infancy)

Genitourinary External Genitalia Male:
inguinal hernia
hypospadias
chordee

Chest Ribs Sternum Clavicles And Scapulae:
broad ribs
broad clavicles

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Nose:
choanal atresia
choanal stenosis

Skin Nails Hair Skin:
cutis marmorata
prominent scalp veins
cutis laxa (infancy)
thin, hypotrophic skin

Neurologic Central Nervous System:
hypotonia
agenesis of the corpus callosum
mental retardation, moderate to severe

Skeletal:
delayed bone age

Head And Neck Ears:
hearing loss, sensorineural
large, floppy ears

Growth Weight:
severe emaciation

Head And Neck Teeth:
dysplastic enamel

Clinical features from OMIM®:

151050 (Updated 05-Mar-2021)

Drugs & Therapeutics for Lenz-Majewski Hyperostotic Dwarfism

Search Clinical Trials , NIH Clinical Center for Lenz-Majewski Hyperostotic Dwarfism

Cochrane evidence based reviews: lenz majewski hyperostotic dwarfism

Genetic Tests for Lenz-Majewski Hyperostotic Dwarfism

Anatomical Context for Lenz-Majewski Hyperostotic Dwarfism

MalaCards organs/tissues related to Lenz-Majewski Hyperostotic Dwarfism:

40
Bone, Tongue, Skin

Publications for Lenz-Majewski Hyperostotic Dwarfism

Articles related to Lenz-Majewski Hyperostotic Dwarfism:

(show all 22)
# Title Authors PMID Year
1
Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. 6 57 61
24241535 2014
2
Expanding the phenotypic spectrum of Lenz-Majewski syndrome: facial palsy, cleft palate and hydrocephalus. 57 6 61
15194948 2004
3
Dysgenesis of corpus callosum in Lenz-Majewski hyperostotic dwarfism. 6 57 61
10756342 2000
4
Skeletal dysplasia syndrome with progeroid appearance, characteristic facial and limb anomalies, multiple synostoses, and distinct skeletal changes: a variant example of the Lenz-Majewski syndrome. 61 57 6
2773987 1989
5
A Japanese patient with a mild Lenz-Majewski syndrome. 61 57
17593321 2007
6
Lenz-Majewski hyperostotic dwarfism: reexamination of the original patient. 61 57
10946362 2000
7
Lenz-Majewski syndrome. 61 57
6611917 1983
8
The Lenz-Majewski hyperostotic dwarfism. A syndrome of multiple congenital anomalies, mental retardation, and progressive skeletal sclerosis. 57 61
894410 1977
9
Craniodiaphyseal dysplasia, a disease or group of diseases? 57
4823202 1974
10
Cutis laxa, skeletal anomalies, and ambiguous genitalia. 57
4809786 1974
11
Multiple congenital abnormalities with diaphyseal dysplasia (Camurati-Engelmann's syndrome). Report of a case. 57
5249155 1969
12
Lenz-Majewski syndrome in a patient from Egypt. 61
31403251 2019
13
Analysis of transgenic zebrafish expressing the Lenz-Majewski syndrome gene PTDSS1 in skeletal cell lineages. 61
31231513 2019
14
Lenz majewskihyperostotic dwarfism: A Pakistani patient with atypical features. 61
29885186 2018
15
Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1. 61
29341480 2018
16
Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-Golgi junctions. 61
27044099 2016
17
Lenz-Majewski syndrome: How a single mutation leads to complex changes in lipid metabolism. 61
30854527 2016
18
Craniovertebral junction stenosis in Lenz-Majewski syndrome. 61
25779830 2015
19
Lenz-Majewski syndrome: Report of a case with novel mutation in PTDSS1 gene. 61
26117586 2015
20
Lenz-Majewski hyperostotic dwarfism with hyperphosphoserinuria from a novel mutation in PTDSS1 encoding phosphatidylserine synthase 1. 61
25363158 2015
21
Inborn errors of metabolism in the biosynthesis and remodelling of phospholipids. 61
25178427 2015
22
Craniotubular dysplasia with severe postnatal growth retardation, mental retardation, ectodermal dysplasia, and loose skin: Lenz-Majewski-like syndrome. 61
9215775 1997

Variations for Lenz-Majewski Hyperostotic Dwarfism

ClinVar genetic disease variations for Lenz-Majewski Hyperostotic Dwarfism:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PTDSS1 NM_014754.3(PTDSS1):c.1058A>G (p.Gln353Arg) SNV Pathogenic 97034 rs587777088 8:97321835-97321835 8:96309607-96309607
2 PTDSS1 NM_014754.3(PTDSS1):c.805C>T (p.Pro269Ser) SNV Pathogenic 97035 rs587777089 8:97316320-97316320 8:96304092-96304092
3 PTDSS1 NM_014754.3(PTDSS1):c.794T>C (p.Leu265Pro) SNV Pathogenic 97036 rs587777090 8:97316309-97316309 8:96304081-96304081
4 PTDSS1 NM_014754.3(PTDSS1):c.953C>T (p.Pro318Leu) SNV Uncertain significance 802426 rs1586200389 8:97318730-97318730 8:96306502-96306502
5 PTDSS1 NM_014754.3(PTDSS1):c.284G>A (p.Arg95Gln) SNV Uncertain significance 429519 rs1131691429 8:97296349-97296349 8:96284121-96284121
6 PTDSS1 NM_014754.3(PTDSS1):c.247A>C (p.Ile83Leu) SNV Uncertain significance 930583 8:97285594-97285594 8:96273366-96273366
7 PTDSS1 NM_014754.3(PTDSS1):c.932T>G (p.Phe311Cys) SNV Uncertain significance 800750 rs1586200380 8:97318709-97318709 8:96306481-96306481

UniProtKB/Swiss-Prot genetic disease variations for Lenz-Majewski Hyperostotic Dwarfism:

73
# Symbol AA change Variation ID SNP ID
1 PTDSS1 p.Leu265Pro VAR_070987 rs587777090
2 PTDSS1 p.Pro269Ser VAR_070988 rs587777089
3 PTDSS1 p.Gln353Arg VAR_070989 rs587777088

Expression for Lenz-Majewski Hyperostotic Dwarfism

Search GEO for disease gene expression data for Lenz-Majewski Hyperostotic Dwarfism.

Pathways for Lenz-Majewski Hyperostotic Dwarfism

Pathways related to Lenz-Majewski Hyperostotic Dwarfism according to KEGG:

36
# Name Kegg Source Accession
1 Glycerophospholipid metabolism hsa00564

GO Terms for Lenz-Majewski Hyperostotic Dwarfism

Cellular components related to Lenz-Majewski Hyperostotic Dwarfism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 9.43 SACM1L PTDSS2 PTDSS1 PCYT1A OSBPL8 CYP2U1
2 endoplasmic reticulum GO:0005783 9.17 SERAC1 SACM1L PTDSS2 PTDSS1 PCYT1A OSBPL8

Biological processes related to Lenz-Majewski Hyperostotic Dwarfism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.5 SERAC1 PTDSS2 PTDSS1 PCYT1A DDHD2 DDHD1
2 phosphatidylinositol biosynthetic process GO:0006661 9.43 SACM1L PI4KA
3 phosphatidic acid biosynthetic process GO:0006654 9.4 DDHD2 DDHD1
4 phosphatidylcholine biosynthetic process GO:0006656 9.37 PCYT1A CHKB
5 positive regulation of mitochondrial fission GO:0090141 9.32 DDHD2 DDHD1
6 CDP-choline pathway GO:0006657 9.26 PCYT1A CHKB
7 phosphatidylserine biosynthetic process GO:0006659 9.16 PTDSS2 PTDSS1
8 phospholipid biosynthetic process GO:0008654 9.02 SERAC1 PTDSS2 PTDSS1 PCYT1A CHKB

Molecular functions related to Lenz-Majewski Hyperostotic Dwarfism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.35 PTDSS2 PTDSS1 PI4KA PCYT1A CHKB
2 phospholipase activity GO:0004620 8.62 DDHD2 DDHD1

Sources for Lenz-Majewski Hyperostotic Dwarfism

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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