MCID: LNZ003
MIFTS: 34

Lenz-Majewski Hyperostotic Dwarfism

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

Aliases & Classifications for Lenz-Majewski Hyperostotic Dwarfism

MalaCards integrated aliases for Lenz-Majewski Hyperostotic Dwarfism:

Name: Lenz-Majewski Hyperostotic Dwarfism 57 59 75 40
Lenz-Majewski Syndrome 57 53 75 37
Lenz Majewski Hyperostotic Dwarfism 53 73
Lmhd 57 75
Multiple Congenital Anomalies, Mental Retardation and Progressive Skeletal Sclerosis 53
Hyperostotic Dwarfism Lenz-Majewski Type 53
Lenz-Majewski Hyperostotic Dysplasia 53
Lms 75

Characteristics:

Orphanet epidemiological data:

59
lenz-majewski hyperostotic dwarfism
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
lenz-majewski hyperostotic dwarfism:
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Lenz-Majewski Hyperostotic Dwarfism

NIH Rare Diseases : 53 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 tongue, and related phenotypes are macrocephaly and hypertelorism

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)

UniProtKB/Swiss-Prot : 75 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.

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 all 19)
# Related Disease Score Top Affiliating Genes
1 limb-mammary syndrome 12.0
2 scarf syndrome 11.5
3 leiomyosarcoma 11.2
4 lateral meningocele syndrome 11.2
5 microcystic lymphatic malformation 11.0
6 lactose intolerance 10.9
7 laurence-moon syndrome 10.9
8 microphthalmia, syndromic 1 10.9
9 dwarfism 10.7
10 short-rib thoracic dysplasia 6 with or without polydactyly 10.3
11 cleft palate, isolated 10.2
12 hydrocephalus 10.2
13 adult syndrome 9.9
14 neural tube defects 9.9
15 aging 9.9
16 neural tube defects, folate-sensitive 9.9
17 testicular cancer 9.9
18 insulin-like growth factor i 9.7
19 brittle bone disorder 9.7

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

Symptoms via clinical synopsis from OMIM:

57
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

GenitourinaryInternal GenitaliaMale:
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

Human phenotypes related to Lenz-Majewski Hyperostotic Dwarfism:

59 32 (show top 50) (show all 94)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000256
2 hypertelorism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000316
3 agenesis of corpus callosum 59 32 occasional (7.5%) Occasional (29-5%) HP:0001274
4 finger syndactyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0006101
5 hydrocephalus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000238
6 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
7 muscular hypotonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001252
8 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
9 kyphosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002808
10 facial palsy 59 32 frequent (33%) Frequent (79-30%) HP:0010628
11 inguinal hernia 59 32 frequent (33%) Frequent (79-30%) HP:0000023
12 mandibular prognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000303
13 macrotia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000400
14 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
15 delayed skeletal maturation 59 32 hallmark (90%) Very frequent (99-80%) HP:0002750
16 thickened calvaria 59 32 hallmark (90%) Very frequent (99-80%) HP:0002684
17 abnormal cortical bone morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0003103
18 thick vermilion border 59 32 frequent (33%) Frequent (79-30%) HP:0012471
19 abnormality of the metaphysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000944
20 short palm 59 32 hallmark (90%) Very frequent (99-80%) HP:0004279
21 joint hyperflexibility 59 32 hallmark (90%) Very frequent (99-80%) HP:0005692
22 cryptorchidism 59 32 frequent (33%) Frequent (79-30%) HP:0000028
23 specific learning disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001328
24 high, narrow palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0002705
25 hyperconvex fingernails 59 32 occasional (7.5%) Occasional (29-5%) HP:0001812
26 hypogonadism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000135
27 broad forehead 59 32 hallmark (90%) Very frequent (99-80%) HP:0000337
28 wide mouth 59 32 frequent (33%) Frequent (79-30%) HP:0000154
29 hypospadias 59 32 frequent (33%) Frequent (79-30%) HP:0000047
30 abnormality of the metacarpal bones 59 32 frequent (33%) Frequent (79-30%) HP:0001163
31 prematurely aged appearance 59 32 hallmark (90%) Very frequent (99-80%) HP:0007495
32 aplasia/hypoplasia of the skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0008065
33 brachydactyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001156
34 abnormality of dental enamel 59 32 hallmark (90%) Very frequent (99-80%) HP:0000682
35 choanal atresia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000453
36 severe short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0003510
37 redundant skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0001582
38 large fontanelles 59 32 hallmark (90%) Very frequent (99-80%) HP:0000239
39 absent septum pellucidum 59 32 occasional (7.5%) Occasional (29-5%) HP:0001331
40 symphalangism affecting the phalanges of the hand 59 32 hallmark (90%) Very frequent (99-80%) HP:0009773
41 hypoplastic fingernail 59 32 occasional (7.5%) Occasional (29-5%) HP:0001804
42 epispadias 59 32 frequent (33%) Frequent (79-30%) HP:0000039
43 bifid uvula 59 32 occasional (7.5%) Occasional (29-5%) HP:0000193
44 submucous cleft hard palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000176
45 delayed cranial suture closure 59 32 hallmark (90%) Very frequent (99-80%) HP:0000270
46 osteopetrosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0011002
47 elbow ankylosis 59 32 frequent (33%) Frequent (79-30%) HP:0003070
48 external genital hypoplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0003241
49 facial hyperostosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0005465
50 femoral hernia 59 32 frequent (33%) Frequent (79-30%) HP:0100541

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:

41
Bone, Skin, Tongue

Publications for Lenz-Majewski Hyperostotic Dwarfism

Articles related to Lenz-Majewski Hyperostotic Dwarfism:

# Title Authors Year
1
Lenz-Majewski Hyperostotic Dwarfism With Hyperphosphoserinuria From A Novel Mutation In PTDSS1 Encoding Phosphatidylserine Synthase 1. ( 25363158 )
2014
2
Dysgenesis of corpus callosum in Lenz-Majewski hyperostotic dwarfism. ( 10756342 )
2000
3
Lenz-Majewski hyperostotic dwarfism: reexamination of the original patient. ( 10946362 )
2000
4
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:

75
# 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:

37
# 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 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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