LPRD1
MCID: LPR012
MIFTS: 34

Leopard Syndrome 1 (LPRD1)

Categories: Cardiovascular diseases, Ear diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Leopard Syndrome 1

MalaCards integrated aliases for Leopard Syndrome 1:

Name: Leopard Syndrome 1 58 76 30 13 6
Lprd1 58 76
Lentiginosis, Cardiomyopathic 58
Multiple Lentigines Syndrome 58
Leopard Syndrome, Type 1 41
Multiple Lentigines 74
Leopard Syndrome 74

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
leopard is an acronym: lentigines, ekg abnormalities, ocular hypertelorism, obstructive cardiomyopathy, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness
allelic to noonan syndrome


HPO:

33
leopard syndrome 1:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Leopard Syndrome 1

OMIM : 58 LEOPARD is an acronym for the manifestations of this syndrome as listed by Gorlin et al. (1969): multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness. (151100)

MalaCards based summary : Leopard Syndrome 1, also known as lprd1, is related to leopard syndrome and lentiginosis, inherited patterned, and has symptoms including hyposmia An important gene associated with Leopard Syndrome 1 is PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11). Affiliated tissues include ovary, heart and skin, and related phenotypes are hypertrophic cardiomyopathy and pulmonic stenosis

UniProtKB/Swiss-Prot : 76 LEOPARD syndrome 1: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.

Related Diseases for Leopard Syndrome 1

Diseases in the Leopard Syndrome family:

Leopard Syndrome 1 Leopard Syndrome 2
Leopard Syndrome 3

Diseases related to Leopard Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 16)
# Related Disease Score Top Affiliating Genes
1 leopard syndrome 11.7
2 lentiginosis, inherited patterned 11.6
3 noonan syndrome with multiple lentigines 11.4
4 lentigines 10.6
5 dyschromatosis universalis hereditaria 1 9.9
6 neurofibromatosis, type i 9.9
7 neurofibromatosis, type iv, of riccardi 9.9
8 noonan syndrome 1 9.9
9 teeth, supernumerary 9.9
10 renal hypodysplasia/aplasia 1 9.9
11 neurofibromatosis-noonan syndrome 9.9
12 renal hypodysplasia/aplasia 3 9.9
13 dermatitis 9.9
14 rhabdomyosarcoma 9.9
15 pseudo-turner syndrome 9.9
16 aorto-right ventricular tunnel 9.9

Graphical network of the top 20 diseases related to Leopard Syndrome 1:



Diseases related to Leopard Syndrome 1

Symptoms & Phenotypes for Leopard Syndrome 1

Human phenotypes related to Leopard Syndrome 1:

33 (show all 41)
# Description HPO Frequency HPO Source Accession
1 hypertrophic cardiomyopathy 33 very rare (1%) HP:0001639
2 pulmonic stenosis 33 very rare (1%) HP:0001642
3 hypertelorism 33 HP:0000316
4 low-set ears 33 HP:0000369
5 short neck 33 HP:0000470
6 pectus excavatum 33 HP:0000767
7 ptosis 33 HP:0000508
8 mandibular prognathia 33 HP:0000303
9 pectus carinatum 33 HP:0000768
10 sensorineural hearing impairment 33 HP:0000407
11 short stature 33 HP:0004322
12 delayed puberty 33 HP:0000823
13 intellectual disability, mild 33 HP:0001256
14 cleft palate 33 HP:0000175
15 strabismus 33 HP:0000486
16 epicanthus 33 HP:0000286
17 cryptorchidism 33 HP:0000028
18 cubitus valgus 33 HP:0002967
19 webbed neck 33 HP:0000465
20 scapular winging 33 HP:0003691
21 protruding ear 33 HP:0000411
22 third degree atrioventricular block 33 HP:0001709
23 kyphoscoliosis 33 HP:0002751
24 depressed nasal ridge 33 HP:0000457
25 hypospadias 33 HP:0000047
26 bundle branch block 33 HP:0011710
27 limited elbow movement 33 HP:0002996
28 spina bifida occulta 33 HP:0003298
29 triangular face 33 HP:0000325
30 multiple lentigines 33 HP:0001003
31 missing ribs 33 HP:0000921
32 micropenis 33 HP:0000054
33 hyposmia 33 HP:0004409
34 unilateral renal agenesis 33 HP:0000122
35 hypoplasia of the ovary 33 HP:0008724
36 cafe-au-lait spot 33 HP:0000957
37 posteriorly rotated ears 33 HP:0000358
38 aplasia of the ovary 33 HP:0010463
39 delayed menarche 33 HP:0012569
40 parietal bossing 33 HP:0000242
41 subvalvular aortic stenosis 33 HP:0001682

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
hypertelorism
ptosis
strabismus
epicanthal folds

Head And Neck Neck:
short neck
pterygium colli

Growth Weight:
short stature

Head And Neck Mouth:
cleft palate

Skeletal Spine:
kyphoscoliosis
spina bifida occulta

Head And Neck Face:
triangular face
prognathism
biparietal bossing

Genitourinary Kidneys:
unilateral renal agenesis

Neurologic Central Nervous System:
mental retardation, mild

Skin Nails Hair Skin:
cafe-au-lait spots
1-5mm dark lentigines (especially neck and trunk)
lentigines may be absent
lentigines may be congenital or develop in first months to years of life
cafe-noir spots (trunk)

Genitourinary Internal Genitalia Female:
absent ovary
hypoplastic ovary

Head And Neck Ears:
low-set ears
posteriorly rotated ears
sensorineural hearing loss
prominent ears

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum
pectus carinatum
winged scapulae
absent ribs

Endocrine Features:
delayed puberty
late menarche

Skeletal Limbs:
cubitus valgus
limited elbow mobility

Cardiovascular Heart:
bundle branch block
subaortic stenosis
pulmonic stenosis (40%)
superior ekg axis (-60 degrees to -120 degrees)
hypertrophic cardiomyopathy (20%)
more
Head And Neck Nose:
hyposmia
broad, flat nose

Growth Other:
growth retardation

Genitourinary External Genitalia Male:
small penis
hypospadias (50%)

Genitourinary Internal Genitalia Male:
cryptorchidism (unilateral or bilateral)

Clinical features from OMIM:

151100

UMLS symptoms related to Leopard Syndrome 1:


hyposmia

Drugs & Therapeutics for Leopard Syndrome 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes Unknown status NCT02486731

Search NIH Clinical Center for Leopard Syndrome 1

Genetic Tests for Leopard Syndrome 1

Genetic tests related to Leopard Syndrome 1:

# Genetic test Affiliating Genes
1 Leopard Syndrome 1 30 PTPN11

Anatomical Context for Leopard Syndrome 1

MalaCards organs/tissues related to Leopard Syndrome 1:

42
Ovary, Heart, Skin

Publications for Leopard Syndrome 1

Articles related to Leopard Syndrome 1:

(show all 32)
# Title Authors Year
1
Lentiginous phenotypes caused by diverse pathogenic genes (SASH1 and PTPN11): clinical and molecular discrimination. ( 27659786 )
2016
2
2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). ( 25173338 )
2014
3
Calcified aorto-right ventricular tunnel in a patient with multiple lentigines syndrome. ( 23287380 )
2013
4
Familial cases of atypical clinical features genetically diagnosed as LEOPARD syndrome (multiple lentigines syndrome). ( 20883402 )
2010
5
Functional effects of PTPN11 (SHP2) mutations causing LEOPARD syndrome on epidermal growth factor-induced phosphoinositide 3-kinase/AKT/glycogen synthase kinase 3beta signaling. ( 20308328 )
2010
6
Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. ( 20535210 )
2010
7
Noonan syndrome: clinical features, diagnosis, and management guidelines. ( 20876176 )
2010
8
Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11. ( 15690106 )
2005
9
Two novel and one recurrent PTPN11 mutations in LEOPARD syndrome. ( 15389709 )
2004
10
Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene. ( 12058348 )
2002
11
Exclusion of candidate genes and loci for multiple lentigines syndrome. ( 12190883 )
2002
12
Multiple lentigines syndrome: a comparison of normal skin and lentiginous skin by electron microscopy and immunohistochemical staining. ( 9675349 )
1998
13
Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis). ( 9222968 )
1997
14
Pigmentary anomalies in the multiple lentigines syndrome: Is it distinct from LEOPARD syndrome? ( 9122064 )
1996
15
Noonan syndrome with café-au-lait spots and multiple lentigines syndrome are not linked to the neurofibromatosis type 1 locus. ( 7586657 )
1995
16
Multiple lentigines syndrome in a Nigerian family. ( 8362457 )
1993
17
Nasopharyngeal rhabdomyosarcoma and multiple lentigines syndrome: a case report. ( 1574034 )
1992
18
The occurrence of supernumerary teeth with isolated, nonfamilial leopard (multiple lentigines) syndrome: report of case. ( 2623465 )
1989
19
Multiple lentigines syndrome in Dominica. ( 3739346 )
1986
20
Cardiopathic and electrocardiographic changes in multiple lentigines syndrome. ( 3825589 )
1986
21
The leopard (multiple lentigines) syndrome: a case report. ( 6621454 )
1983
22
Additional comments on the ulcer-multiple lentigines syndrome. ( 7065011 )
1982
23
Factitial dermatitis as the presenting sign of multiple lentigines syndrome. Therapeutic effect of autodermabrasion. ( 7065683 )
1982
24
Giant melanosomes in multiple lentigines syndrome. ( 848980 )
1977
25
Multiple lentigines syndrome. Case report and review of the literature. ( 1258892 )
1976
26
The multiple lentigines syndrome. ( 4685582 )
1973
27
Multiple lentigines syndrome. A case report of a rare familial syndrome with orthopaedic considerations. ( 4774496 )
1973
28
Lentiginosis profusa syndrome (multiple lentigines syndrome). II. Histological findings, modified Crowe's sign, and possible relationship to von Recklinghausen's disease. ( 4109279 )
1971
29
The leopard (multiple lentigines) syndrome revisited. ( 4398858 )
1971
30
Lentiginosis profusa syndrome (multiple lentigines syndrome). ( 5000391 )
1971
31
The Leopard (multiple lentigines) syndrome revisited. ( 5173334 )
1971
32
Multiple lentigines syndrome: new findings of hypogonadotrophism, hyposmia, and unilateral renal agenesis. ( 5577185 )
1971

Variations for Leopard Syndrome 1

UniProtKB/Swiss-Prot genetic disease variations for Leopard Syndrome 1:

76
# Symbol AA change Variation ID SNP ID
1 PTPN11 p.Tyr279Cys VAR_015614 rs121918456
2 PTPN11 p.Thr472Met VAR_015621 rs121918457
3 PTPN11 p.Tyr279Ser VAR_027188 rs121918456
4 PTPN11 p.Ala465Thr VAR_027190 rs121918468
5 PTPN11 p.Gly468Ala VAR_027191 rs121918469
6 PTPN11 p.Arg502Leu VAR_027192 rs397507542
7 PTPN11 p.Arg502Trp VAR_027193 rs397507541
8 PTPN11 p.Gln510Pro VAR_027194 rs397509345
9 PTPN11 p.Gln514Pro VAR_027196 rs121918470
10 PTPN11 p.Gln514Glu VAR_076499 rs397507549

ClinVar genetic disease variations for Leopard Syndrome 1:

6 (show top 50) (show all 72)
# Gene Variation Type Significance SNP ID Assembly Location
1 PTPN11 NM_002834.4(PTPN11): c.236A> G (p.Gln79Arg) single nucleotide variant Pathogenic rs121918466 GRCh37 Chromosome 12, 112888220: 112888220
2 PTPN11 NM_002834.4(PTPN11): c.236A> G (p.Gln79Arg) single nucleotide variant Pathogenic rs121918466 GRCh38 Chromosome 12, 112450416: 112450416
3 PTPN11 NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr) single nucleotide variant Pathogenic rs121918468 GRCh37 Chromosome 12, 112926248: 112926248
4 PTPN11 NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr) single nucleotide variant Pathogenic rs121918468 GRCh38 Chromosome 12, 112488444: 112488444
5 PTPN11 NM_002834.4(PTPN11): c.1391G> C (p.Gly464Ala) single nucleotide variant Pathogenic rs121918469 GRCh37 Chromosome 12, 112926258: 112926258
6 PTPN11 NM_002834.4(PTPN11): c.1391G> C (p.Gly464Ala) single nucleotide variant Pathogenic rs121918469 GRCh38 Chromosome 12, 112488454: 112488454
7 PTPN11 NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro) single nucleotide variant Pathogenic rs121918470 GRCh37 Chromosome 12, 112926909: 112926909
8 PTPN11 NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro) single nucleotide variant Pathogenic rs121918470 GRCh38 Chromosome 12, 112489105: 112489105
9 PTPN11 NM_002834.4(PTPN11): c.1678C> T (p.Leu560Phe) single nucleotide variant Likely benign rs397516797 GRCh37 Chromosome 12, 112940026: 112940026
10 PTPN11 NM_002834.4(PTPN11): c.1678C> T (p.Leu560Phe) single nucleotide variant Likely benign rs397516797 GRCh38 Chromosome 12, 112502222: 112502222
11 PTPN11 NM_002834.4(PTPN11): c.836A> C (p.Tyr279Ser) single nucleotide variant Pathogenic rs121918456 GRCh37 Chromosome 12, 112910827: 112910827
12 PTPN11 NM_002834.4(PTPN11): c.836A> C (p.Tyr279Ser) single nucleotide variant Pathogenic rs121918456 GRCh38 Chromosome 12, 112473023: 112473023
13 PTPN11 NM_002834.4(PTPN11): c.1682C> T (p.Pro561Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs141140214 GRCh38 Chromosome 12, 112502226: 112502226
14 PTPN11 NM_002834.4(PTPN11): c.1682C> T (p.Pro561Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs141140214 GRCh37 Chromosome 12, 112940030: 112940030
15 PTPN11 NM_002834.4(PTPN11): c.473G> C (p.Gly158Ala) single nucleotide variant Uncertain significance rs1555267825 GRCh37 Chromosome 12, 112891139: 112891139
16 PTPN11 NM_002834.4(PTPN11): c.473G> C (p.Gly158Ala) single nucleotide variant Uncertain significance rs1555267825 GRCh38 Chromosome 12, 112453335: 112453335
17 PTPN11 NM_002834.4(PTPN11): c.1579C> T (p.Arg527Cys) single nucleotide variant Uncertain significance rs191525506 GRCh37 Chromosome 12, 112926959: 112926959
18 PTPN11 NM_002834.4(PTPN11): c.1579C> T (p.Arg527Cys) single nucleotide variant Uncertain significance rs191525506 GRCh38 Chromosome 12, 112489155: 112489155
19 PTPN11 NM_002834.4(PTPN11): c.1599+4C> A single nucleotide variant Uncertain significance rs142606486 GRCh37 Chromosome 12, 112926983: 112926983
20 PTPN11 NM_002834.4(PTPN11): c.1599+4C> A single nucleotide variant Uncertain significance rs142606486 GRCh38 Chromosome 12, 112489179: 112489179
21 PTPN11 NM_002834.4(PTPN11): c.1507G> C (p.Gly503Arg) single nucleotide variant Pathogenic rs397507545 GRCh38 Chromosome 12, 112489083: 112489083
22 PTPN11 NM_002834.4(PTPN11): c.1507G> C (p.Gly503Arg) single nucleotide variant Pathogenic rs397507545 GRCh37 Chromosome 12, 112926887: 112926887
23 PTPN11 NM_002834.4(PTPN11): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs397507542 GRCh38 Chromosome 12, 112489069: 112489069
24 PTPN11 NM_002834.4(PTPN11): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs397507542 GRCh37 Chromosome 12, 112926873: 112926873
25 PTPN11 NM_002834.4(PTPN11): c.1492C> T (p.Arg498Trp) single nucleotide variant Pathogenic rs397507541 GRCh38 Chromosome 12, 112489068: 112489068
26 PTPN11 NM_002834.4(PTPN11): c.1492C> T (p.Arg498Trp) single nucleotide variant Pathogenic rs397507541 GRCh37 Chromosome 12, 112926872: 112926872
27 PTPN11 NM_002834.4(PTPN11): c.1048T> G (p.Ser350Ala) single nucleotide variant Uncertain significance rs146571700 GRCh38 Chromosome 12, 112477971: 112477971
28 PTPN11 NM_002834.4(PTPN11): c.1048T> G (p.Ser350Ala) single nucleotide variant Uncertain significance rs146571700 GRCh37 Chromosome 12, 112915775: 112915775
29 PTPN11 NM_002834.4(PTPN11): c.853T> C (p.Phe285Leu) single nucleotide variant Pathogenic/Likely pathogenic rs397507531 GRCh38 Chromosome 12, 112473040: 112473040
30 PTPN11 NM_002834.4(PTPN11): c.853T> C (p.Phe285Leu) single nucleotide variant Pathogenic/Likely pathogenic rs397507531 GRCh37 Chromosome 12, 112910844: 112910844
31 PTPN11 NM_002834.4(PTPN11): c.417G> C (p.Glu139Asp) single nucleotide variant Pathogenic rs397507520 GRCh38 Chromosome 12, 112453279: 112453279
32 PTPN11 NM_002834.4(PTPN11): c.417G> C (p.Glu139Asp) single nucleotide variant Pathogenic rs397507520 GRCh37 Chromosome 12, 112891083: 112891083
33 PTPN11 NM_002834.4(PTPN11): c.228G> T (p.Glu76Asp) single nucleotide variant Pathogenic rs397507514 GRCh38 Chromosome 12, 112450408: 112450408
34 PTPN11 NM_002834.4(PTPN11): c.228G> T (p.Glu76Asp) single nucleotide variant Pathogenic rs397507514 GRCh37 Chromosome 12, 112888212: 112888212
35 PTPN11 NM_002834.4(PTPN11): c.181G> A (p.Asp61Asn) single nucleotide variant Pathogenic rs397507510 GRCh38 Chromosome 12, 112450361: 112450361
36 PTPN11 NM_002834.4(PTPN11): c.181G> A (p.Asp61Asn) single nucleotide variant Pathogenic rs397507510 GRCh37 Chromosome 12, 112888165: 112888165
37 PTPN11 NM_002834.4(PTPN11): c.174C> G (p.Asn58Lys) single nucleotide variant Pathogenic/Likely pathogenic rs397507506 GRCh38 Chromosome 12, 112450354: 112450354
38 PTPN11 NM_002834.4(PTPN11): c.174C> G (p.Asn58Lys) single nucleotide variant Pathogenic/Likely pathogenic rs397507506 GRCh37 Chromosome 12, 112888158: 112888158
39 PTPN11 NM_002834.4(PTPN11): c.172A> G (p.Asn58Asp) single nucleotide variant Pathogenic rs397507505 GRCh38 Chromosome 12, 112450352: 112450352
40 PTPN11 NM_002834.4(PTPN11): c.172A> G (p.Asn58Asp) single nucleotide variant Pathogenic rs397507505 GRCh37 Chromosome 12, 112888156: 112888156
41 PTPN11 NM_002834.4(PTPN11): c.218C> T (p.Thr73Ile) single nucleotide variant Pathogenic rs121918462 GRCh38 Chromosome 12, 112450398: 112450398
42 PTPN11 NM_002834.4(PTPN11): c.218C> T (p.Thr73Ile) single nucleotide variant Pathogenic rs121918462 GRCh37 Chromosome 12, 112888202: 112888202
43 PTPN11 NM_002834.4(PTPN11): c.188A> G (p.Tyr63Cys) single nucleotide variant Pathogenic rs121918459 GRCh38 Chromosome 12, 112450368: 112450368
44 PTPN11 NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met) single nucleotide variant Pathogenic rs121918457 GRCh38 Chromosome 12, 112488466: 112488466
45 PTPN11 NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met) single nucleotide variant Pathogenic rs121918457 GRCh37 Chromosome 12, 112926270: 112926270
46 PTPN11 NM_002834.4(PTPN11): c.184T> G (p.Tyr62Asp) single nucleotide variant Pathogenic rs121918460 GRCh38 Chromosome 12, 112450364: 112450364
47 PTPN11 NM_002834.4(PTPN11): c.188A> G (p.Tyr63Cys) single nucleotide variant Pathogenic rs121918459 GRCh37 Chromosome 12, 112888172: 112888172
48 PTPN11 NM_002834.4(PTPN11): c.184T> G (p.Tyr62Asp) single nucleotide variant Pathogenic rs121918460 GRCh37 Chromosome 12, 112888168: 112888168
49 PTPN11 NM_002834.4(PTPN11): c.836A> G (p.Tyr279Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918456 GRCh38 Chromosome 12, 112473023: 112473023
50 PTPN11 NM_002834.4(PTPN11): c.836A> G (p.Tyr279Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918456 GRCh37 Chromosome 12, 112910827: 112910827

Expression for Leopard Syndrome 1

Search GEO for disease gene expression data for Leopard Syndrome 1.

Pathways for Leopard Syndrome 1

GO Terms for Leopard Syndrome 1

Sources for Leopard Syndrome 1

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