MCID: LPR012
MIFTS: 33

Leopard Syndrome 1

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

Aliases & Classifications for Leopard Syndrome 1

MalaCards integrated aliases for Leopard Syndrome 1:

Name: Leopard Syndrome 1 53 71 28 13
Multiple Lentigines 28 69
Lprd1 53 71
Lentiginosis, Cardiomyopathic 53
Multiple Lentigines Syndrome 53
Leopard Syndrome 69

Characteristics:

OMIM:

53
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:

31
leopard syndrome 1:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Leopard Syndrome 1

OMIM : 53 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 multiple lentigines, is related to leopard syndrome and noonan syndrome with multiple lentigines, and has symptoms including hyposmia, hypertelorism and low-set ears. An important gene associated with Leopard Syndrome 1 is PTPN11 (Protein Tyrosine Phosphatase, Non-Receptor Type 11). Affiliated tissues include ovary and heart.

UniProtKB/Swiss-Prot : 71 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:

# Related Disease Score Top Affiliating Genes
1 leopard syndrome 11.5
2 noonan syndrome with multiple lentigines 11.2

Symptoms & Phenotypes for Leopard Syndrome 1

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Nose:
hyposmia
broad, flat nose

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

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

Endocrine Features:
delayed puberty
late menarche

Skeletal Limbs:
cubitus valgus
limited elbow mobility

Skeletal Spine:
spina bifida occulta
kyphoscoliosis

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 Eyes:
hypertelorism
ptosis
strabismus
epicanthal folds

Head And Neck Neck:
short neck
pterygium colli

Growth Weight:
short stature

Head And Neck Mouth:
cleft palate

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 Face:
triangular face
prognathism
biparietal bossing

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

Human phenotypes related to Leopard Syndrome 1:

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

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 Not yet recruiting 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 28 PTPN11
2 Multiple Lentigines 28

Anatomical Context for Leopard Syndrome 1

MalaCards organs/tissues related to Leopard Syndrome 1:

38
Ovary, Heart

Publications for Leopard Syndrome 1

Articles related to Leopard Syndrome 1:

(show all 27)
# Title Authors Year
1
Noonan syndrome with multiple lentigines and associated craniosynostosis. ( 29356064 )
2018
2
In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy. ( 28582432 )
2017
3
Heterozygous deletion of AKT1 rescues cardiac contractility, but not hypertrophy, in a mouse model of Noonan Syndrome with Multiple Lentigines. ( 28911943 )
2017
4
Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. ( 28483241 )
2017
5
Noonan syndrome with multiple lentigines with PTPN11 (T468M) gene mutation accompanied with solitary granular cell tumor. ( 28681392 )
2017
6
Urticaria Pigmentosa Mimicking Multiple Lentigine-like Brownish Macules in a 22-Month-Old Boy. ( 28480643 )
2017
7
A Novel De novo Mutation of the SASH1 Gene in a Chinese Family with Multiple Lentigines. ( 27840890 )
2017
8
Hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26952712 )
2016
9
Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines. ( 27348588 )
2016
10
Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines. ( 27238887 )
2016
11
Elevated calcium transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan Syndrome with Multiple Lentigines. ( 25724491 )
2015
12
Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: Palliative treatment with a rapamycin analog. ( 25708222 )
2015
13
A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines. ( 25423878 )
2015
14
Pathogenesis of Multiple Lentigines in LEOPARD Syndrome with PTPN11 Gene Mutation. ( 25917897 )
2015
15
Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26337637 )
2015
16
Calcified aorto-right ventricular tunnel in a patient with multiple lentigines syndrome. ( 23287380 )
2013
17
Extensive abdominal lipomatosis in a patient with Noonan/LEOPARD syndrome (Noonan syndrome-Multiple Lentigines). ( 22528600 )
2012
18
Familial cases of atypical clinical features genetically diagnosed as LEOPARD syndrome (multiple lentigines syndrome). ( 20883402 )
2010
19
Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome. ( 15121796 )
2004
20
A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome. ( 15470362 )
2004
21
Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene. ( 12058348 )
2002
22
Multiple lentigines and testicular microlithiasis. ( 11167985 )
2000
23
Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis). ( 9222968 )
1997
24
Pigmentary anomalies in the multiple lentigines syndrome: Is it distinct from LEOPARD syndrome? ( 9122064 )
1996
25
Multiple lentigines (Leopard) syndrome with Chiara I malformation. ( 7560446 )
1995
26
Noonan syndrome with cafAc-au-lait spots and multiple lentigines syndrome are not linked to the neurofibromatosis type 1 locus. ( 7586657 )
1995
27
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:

71
# 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 all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 PTPN11 NM_002834.4(PTPN11): c.214G> T (p.Ala72Ser) single nucleotide variant Pathogenic rs121918453 GRCh37 Chromosome 12, 112888198: 112888198
2 PTPN11 NM_002834.4(PTPN11): c.215C> G (p.Ala72Gly) single nucleotide variant Pathogenic rs121918454 GRCh37 Chromosome 12, 112888199: 112888199
3 PTPN11 NM_002834.4(PTPN11): c.922A> G (p.Asn308Asp) single nucleotide variant Pathogenic rs28933386 GRCh37 Chromosome 12, 112915523: 112915523
4 PTPN11 NM_002834.4(PTPN11): c.923A> G (p.Asn308Ser) single nucleotide variant Pathogenic rs121918455 GRCh37 Chromosome 12, 112915524: 112915524
5 PTPN11 NM_002834.4(PTPN11): c.836A> G (p.Tyr279Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918456 GRCh37 Chromosome 12, 112910827: 112910827
6 PTPN11 NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met) single nucleotide variant Pathogenic rs121918457 GRCh37 Chromosome 12, 112926270: 112926270
7 PTPN11 NM_002834.4(PTPN11): c.188A> G (p.Tyr63Cys) single nucleotide variant Pathogenic rs121918459 GRCh37 Chromosome 12, 112888172: 112888172
8 PTPN11 NM_002834.4(PTPN11): c.218C> T (p.Thr73Ile) single nucleotide variant Pathogenic rs121918462 GRCh37 Chromosome 12, 112888202: 112888202
9 PTPN11 NM_002834.4(PTPN11): c.236A> G (p.Gln79Arg) single nucleotide variant Pathogenic rs121918466 GRCh37 Chromosome 12, 112888220: 112888220
10 PTPN11 NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr) single nucleotide variant Pathogenic rs121918468 GRCh37 Chromosome 12, 112926248: 112926248
11 PTPN11 NM_002834.4(PTPN11): c.1391G> C (p.Gly464Ala) single nucleotide variant Pathogenic rs121918469 GRCh37 Chromosome 12, 112926258: 112926258
12 PTPN11 NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro) single nucleotide variant Pathogenic rs121918470 GRCh37 Chromosome 12, 112926909: 112926909
13 PTPN11 NM_002834.4(PTPN11): c.174C> G (p.Asn58Lys) single nucleotide variant Pathogenic/Likely pathogenic rs397507506 GRCh37 Chromosome 12, 112888158: 112888158
14 PTPN11 NM_002834.4(PTPN11): c.181G> A (p.Asp61Asn) single nucleotide variant Pathogenic rs397507510 GRCh37 Chromosome 12, 112888165: 112888165
15 PTPN11 NM_002834.4(PTPN11): c.417G> C (p.Glu139Asp) single nucleotide variant Pathogenic rs397507520 GRCh37 Chromosome 12, 112891083: 112891083
16 PTPN11 NM_002834.4(PTPN11): c.1492C> T (p.Arg498Trp) single nucleotide variant Pathogenic rs397507541 GRCh37 Chromosome 12, 112926872: 112926872
17 PTPN11 NM_002834.4(PTPN11): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs397507542 GRCh37 Chromosome 12, 112926873: 112926873
18 PTPN11 NM_002834.4(PTPN11): c.1507G> C (p.Gly503Arg) single nucleotide variant Pathogenic rs397507545 GRCh37 Chromosome 12, 112926887: 112926887
19 PTPN11 NM_002834.4(PTPN11): c.1517A> C (p.Gln506Pro) single nucleotide variant Pathogenic rs397507548 GRCh37 Chromosome 12, 112926897: 112926897
20 PTPN11 NM_002834.4(PTPN11): c.1528C> G (p.Gln510Glu) single nucleotide variant Pathogenic rs397507549 GRCh37 Chromosome 12, 112926908: 112926908
21 PTPN11 NM_002834.4(PTPN11): c.1530G> C (p.Gln510His) single nucleotide variant Pathogenic rs397507550 GRCh37 Chromosome 12, 112926910: 112926910
22 PTPN11 NM_002834.4(PTPN11): c.836A> C (p.Tyr279Ser) single nucleotide variant 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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
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29 HGMD
30 HMDB
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42 MESH via Orphanet
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58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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