LMHD
MCID: LNZ003
MIFTS: 36

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 58 60 76 41
Lenz-Majewski Syndrome 58 54 76 38
Lenz Majewski Hyperostotic Dwarfism 54 74
Lmhd 58 76
Multiple Congenital Anomalies, Mental Retardation and Progressive Skeletal Sclerosis 54
Hyperostotic Dwarfism Lenz-Majewski Type 54
Lenz-Majewski Hyperostotic Dysplasia 54
Lms 76

Characteristics:

Orphanet epidemiological data:

60
lenz-majewski hyperostotic dwarfism
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal dominant

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


HPO:

33
lenz-majewski hyperostotic dwarfism:
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Lenz-Majewski Hyperostotic Dwarfism

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2658Disease definitionLenz-Majewski hyperostotic dwarfism is an 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 dominantde 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 scarf syndrome. An important gene associated with Lenz-Majewski Hyperostotic Dwarfism is PTDSS1 (Phosphatidylserine Synthase 1), and among its related pathways/superpathways is Glycerophospholipid metabolism. Affiliated tissues include bone, skin and prostate, and related phenotypes are macrocephaly and hypertelorism

OMIM : 58 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)

UniProtKB/Swiss-Prot : 76 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 : 77 Lenz–Majewski syndrome is a skin condition characterized by hyperostosis, craniodiaphyseal dysplasia,... 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 53)
# Related Disease Score Top Affiliating Genes
1 limb-mammary syndrome 12.3
2 scarf syndrome 11.7
3 lateral meningocele syndrome 11.4
4 microcystic lymphatic malformation 11.3
5 laurence-moon syndrome 11.1
6 lactose intolerance 11.1
7 dwarfism 10.9
8 short-rib thoracic dysplasia 6 with or without polydactyly 10.8
9 spondyloenchondrodysplasia 10.6
10 hydrocephalus 10.3
11 facial paralysis 10.3
12 leiomyosarcoma 10.2
13 lentigines 10.0
14 prostate cancer 10.0
15 neural tube defects 10.0
16 retinitis pigmentosa 10.0
17 neural tube defects, folate-sensitive 10.0
18 prostate cancer, hereditary, 8 10.0
19 body mass index quantitative trait locus 1 10.0
20 prostate cancer, hereditary, 6 10.0
21 blood group, junior system 10.0
22 sclerosing cholangitis, neonatal 10.0
23 testicular cancer 10.0
24 polymyositis 10.0
25 adult syndrome 9.9
26 blood group--wright antigen 9.9
27 cleft palate, isolated 9.9
28 retinoblastoma 9.9
29 rheumatoid arthritis 9.9
30 disorganization, mouse, homolog of 9.9
31 insulin-like growth factor i 9.9
32 brittle bone disorder 9.9
33 gastrointestinal stromal tumor 9.9
34 anxiety 9.9
35 alpha-1-antitrypsin deficiency 9.9
36 burns 9.9
37 cataract 9.9
38 pancreas adenocarcinoma 9.9
39 atrial fibrillation 9.9
40 obstructive nephropathy 9.9
41 adenoid cystic carcinoma 9.9
42 japanese encephalitis 9.9
43 sarcoma 9.9
44 anus cancer 9.9
45 adenocarcinoma 9.9
46 complex regional pain syndrome 9.9
47 endometrial stromal sarcoma 9.9
48 paraplegia 9.9
49 muscular atrophy 9.9
50 col1a1/2-related osteogenesis imperfecta 9.9

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:

60 33 (show top 50) (show all 94)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0000256
2 hypertelorism 60 33 hallmark (90%) Very frequent (99-80%) HP:0000316
3 finger syndactyly 60 33 hallmark (90%) Very frequent (99-80%) HP:0006101
4 intellectual disability 60 33 hallmark (90%) Very frequent (99-80%) HP:0001249
5 mandibular prognathia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000303
6 macrotia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000400
7 global developmental delay 60 33 hallmark (90%) Very frequent (99-80%) HP:0001263
8 delayed skeletal maturation 60 33 hallmark (90%) Very frequent (99-80%) HP:0002750
9 thickened calvaria 60 33 hallmark (90%) Very frequent (99-80%) HP:0002684
10 abnormal cortical bone morphology 60 33 hallmark (90%) Very frequent (99-80%) HP:0003103
11 abnormality of the metaphysis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000944
12 short palm 60 33 hallmark (90%) Very frequent (99-80%) HP:0004279
13 joint hyperflexibility 60 33 hallmark (90%) Very frequent (99-80%) HP:0005692
14 specific learning disability 60 33 hallmark (90%) Very frequent (99-80%) HP:0001328
15 broad forehead 60 33 hallmark (90%) Very frequent (99-80%) HP:0000337
16 prematurely aged appearance 60 33 hallmark (90%) Very frequent (99-80%) HP:0007495
17 aplasia/hypoplasia of the skin 60 33 hallmark (90%) Very frequent (99-80%) HP:0008065
18 brachydactyly 60 33 hallmark (90%) Very frequent (99-80%) HP:0001156
19 abnormality of dental enamel 60 33 hallmark (90%) Very frequent (99-80%) HP:0000682
20 choanal atresia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000453
21 severe short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0003510
22 redundant skin 60 33 hallmark (90%) Very frequent (99-80%) HP:0001582
23 large fontanelles 60 33 hallmark (90%) Very frequent (99-80%) HP:0000239
24 symphalangism affecting the phalanges of the hand 60 33 hallmark (90%) Very frequent (99-80%) HP:0009773
25 delayed cranial suture closure 60 33 hallmark (90%) Very frequent (99-80%) HP:0000270
26 osteopetrosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0011002
27 facial hyperostosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0005465
28 aplastic clavicle 33 hallmark (90%) HP:0006660
29 facial palsy 60 33 frequent (33%) Frequent (79-30%) HP:0010628
30 inguinal hernia 60 33 frequent (33%) Frequent (79-30%) HP:0000023
31 thick vermilion border 60 33 frequent (33%) Frequent (79-30%) HP:0012471
32 cryptorchidism 60 33 frequent (33%) Frequent (79-30%) HP:0000028
33 wide mouth 60 33 frequent (33%) Frequent (79-30%) HP:0000154
34 hypospadias 60 33 frequent (33%) Frequent (79-30%) HP:0000047
35 abnormality of the metacarpal bones 60 33 frequent (33%) Frequent (79-30%) HP:0001163
36 epispadias 60 33 frequent (33%) Frequent (79-30%) HP:0000039
37 elbow ankylosis 60 33 frequent (33%) Frequent (79-30%) HP:0003070
38 femoral hernia 60 33 frequent (33%) Frequent (79-30%) HP:0100541
39 abnormal nasolacrimal system morphology 33 frequent (33%) HP:0000614
40 agenesis of corpus callosum 60 33 occasional (7.5%) Occasional (29-5%) HP:0001274
41 hydrocephalus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000238
42 muscular hypotonia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001252
43 scoliosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002650
44 kyphosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002808
45 high, narrow palate 60 33 occasional (7.5%) Occasional (29-5%) HP:0002705
46 hyperconvex fingernails 60 33 occasional (7.5%) Occasional (29-5%) HP:0001812
47 hypogonadism 60 33 occasional (7.5%) Occasional (29-5%) HP:0000135
48 absent septum pellucidum 60 33 occasional (7.5%) Occasional (29-5%) HP:0001331
49 hypoplastic fingernail 60 33 occasional (7.5%) Occasional (29-5%) HP:0001804
50 bifid uvula 60 33 occasional (7.5%) Occasional (29-5%) HP:0000193

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
hypertelorism
nasolacrimal duct stenosis

Genitourinary External Genitalia Male:
inguinal hernia
hypospadias
chordee

Chest Ribs Sternum Clavicles And Scapulae:
broad ribs
broad clavicles

Skeletal Limbs:
diaphyseal thickening
knee flexion contracture
elbow flexion contractures
metaphyseal hypostosis
long, flared metaphyses
more
Abdomen Gastrointestinal:
anteriorly placed anus

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

Skeletal:
delayed bone age

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

Growth Weight:
severe emaciation

Head And Neck Teeth:
dysplastic enamel

Skin Nails Hair Hair:
sparse hair (infancy)

Growth Other:
failure to thrive
intrauterine growth retardation

Head And Neck Face:
micrognathia
broad, prominent forehead

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

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

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

Clinical features from OMIM:

151050

Drugs & Therapeutics for Lenz-Majewski Hyperostotic Dwarfism

Search Clinical Trials , NIH Clinical Center for 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:

42
Bone, Skin, Prostate, Tongue, Pancreas, Thymus

Publications for Lenz-Majewski Hyperostotic Dwarfism

Articles related to Lenz-Majewski Hyperostotic Dwarfism:

(show all 12)
# Title Authors Year
1
Lenz-Majewski syndrome: How a single mutation leads to complex changes in lipid metabolism. ( 30854527 )
2016
2
Lenz-Majewski hyperostotic dwarfism with hyperphosphoserinuria from a novel mutation in PTDSS1 encoding phosphatidylserine synthase 1. ( 25363158 )
2015
3
Craniovertebral junction stenosis in Lenz-Majewski syndrome. ( 25779830 )
2015
4
Lenz-Majewski syndrome: Report of a case with novel mutation in PTDSS1 gene. ( 26117586 )
2015
5
Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. ( 24241535 )
2014
6
A Japanese patient with a mild Lenz-Majewski syndrome. ( 17593321 )
2007
7
Expanding the phenotypic spectrum of Lenz-Majewski syndrome: facial palsy, cleft palate and hydrocephalus. ( 15194948 )
2004
8
Dysgenesis of corpus callosum in Lenz-Majewski hyperostotic dwarfism. ( 10756342 )
2000
9
Lenz-Majewski hyperostotic dwarfism: reexamination of the original patient. ( 10946362 )
2000
10
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. ( 2773987 )
1989
11
Lenz-Majewski syndrome. ( 6611917 )
1983
12
The Lenz-Majewski hyperostotic dwarfism. A syndrome of multiple congenital anomalies, mental retardation, and progressive skeletal sclerosis. ( 894410 )
1977

Variations for Lenz-Majewski Hyperostotic Dwarfism

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

76
# 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

ClinVar genetic disease variations for Lenz-Majewski Hyperostotic Dwarfism:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PTDSS1 NM_014754.2(PTDSS1): c.1058A> G (p.Gln353Arg) single nucleotide variant Pathogenic rs587777088 GRCh37 Chromosome 8, 97321835: 97321835
2 PTDSS1 NM_014754.2(PTDSS1): c.1058A> G (p.Gln353Arg) single nucleotide variant Pathogenic rs587777088 GRCh38 Chromosome 8, 96309607: 96309607
3 PTDSS1 NM_014754.2(PTDSS1): c.805C> T (p.Pro269Ser) single nucleotide variant Pathogenic rs587777089 GRCh37 Chromosome 8, 97316320: 97316320
4 PTDSS1 NM_014754.2(PTDSS1): c.805C> T (p.Pro269Ser) single nucleotide variant Pathogenic rs587777089 GRCh38 Chromosome 8, 96304092: 96304092
5 PTDSS1 NM_014754.2(PTDSS1): c.794T> C (p.Leu265Pro) single nucleotide variant Pathogenic rs587777090 GRCh37 Chromosome 8, 97316309: 97316309
6 PTDSS1 NM_014754.2(PTDSS1): c.794T> C (p.Leu265Pro) single nucleotide variant Pathogenic rs587777090 GRCh38 Chromosome 8, 96304081: 96304081

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:

38
# Name Kegg Source Accession
1 Glycerophospholipid metabolism hsa00564

GO Terms for Lenz-Majewski Hyperostotic Dwarfism

Sources for Lenz-Majewski Hyperostotic Dwarfism

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....