NNMS
MCID: NVL003
MIFTS: 42

Nivelon-Nivelon-Mabille Syndrome (NNMS)

Categories: Bone diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Nivelon-Nivelon-Mabille Syndrome

MalaCards integrated aliases for Nivelon-Nivelon-Mabille Syndrome:

Name: Nivelon-Nivelon-Mabille Syndrome 57 12 58 36
Chondrodysplasia-Pseudohermaphroditism Syndrome 57 12 6 15
Chondrodysplasia-Disorder of Sex Development Syndrome 12 58
Nivelon Nivelon Mabille Syndrome 44
Nnms 57

Characteristics:

Orphanet epidemiological data:

58
chondrodysplasia-disorder of sex development syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal;

OMIM®:

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


HPO:

31
nivelon-nivelon-mabille syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Rare gynaecological and obstetric diseases
Rare bone diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Nivelon-Nivelon-Mabille Syndrome

KEGG : 36 Nivelon-Nivelon-Mabille syndrome (NNMS), previously known as chondrodysplasia-pseudohermaphrodism syndrome, is a rare autosomal recessive syndrome characterized by microcephaly, early infantile onset seizures, and cerebellar vermis hypoplasia. It has been reported that mutations in the hedgehog acyl-transferase gene (HHAT) cause NNMS.

MalaCards based summary : Nivelon-Nivelon-Mabille Syndrome, also known as chondrodysplasia-pseudohermaphroditism syndrome, is related to ancylostomiasis and 45,x/46,xy mixed gonadal dysgenesis. An important gene associated with Nivelon-Nivelon-Mabille Syndrome is HHAT (Hedgehog Acyltransferase), and among its related pathways/superpathways are Endochondral Ossification and Hedgehog signaling pathway (KEGG). Affiliated tissues include eye, bone and brain, and related phenotypes are intellectual disability and macrotia

Disease Ontology : 12 A syndrome characterized by the clinical features of 46,XY complete gonadal dysgenesis in association with severe dwarfism with generalized chondrodysplasia.

OMIM® : 57 Nivelon-Nivelon-Mabille syndrome (NNMS) is characterized by progressive microcephaly, vermis hypoplasia, and skeletal dysplasia. Variable features include infantile-onset seizures, dwarfism, generalized chondrodysplasia, and micromelia (Abdel-Salam et al., 2019). (600092) (Updated 05-Mar-2021)

Related Diseases for Nivelon-Nivelon-Mabille Syndrome

Diseases related to Nivelon-Nivelon-Mabille Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 53)
# Related Disease Score Top Affiliating Genes
1 ancylostomiasis 10.2 NR5A1 HHAT
2 45,x/46,xy mixed gonadal dysgenesis 10.1 WNT4 NR0B1
3 acrocapitofemoral dysplasia 10.1 WWC3 IHH
4 juvenile type testicular granulosa cell tumor 10.1 WT1 FOXL2
5 testicular granulosa cell tumor 10.1 WT1 FOXL2
6 mullerian aplasia and hyperandrogenism 10.1 WNT4 FOXL2
7 steroid inherited metabolic disorder 10.0 NR5A1 NR0B1
8 corticosterone methyloxidase type i deficiency 10.0 NR5A1 NR0B1
9 brachydactyly, type a1, b 10.0 PTCH1 IHH
10 mayer-rokitansky-kuster-hauser syndrome 10.0 WT1 WNT4
11 amenorrhea 10.0 WNT4 NR5A1 FOXL2
12 microcystic stromal tumor 9.9 WT1 NR5A1 FOXL2
13 ovarian sex-cord stromal tumor 9.9 WT1 NR5A1 FOXL2
14 holoprosencephaly 7 9.9 PTCH1 IHH HHAT
15 micronodular basal cell carcinoma 9.9 SOX9 PTCH1
16 sex cord-gonadal stromal tumor 9.9 WT1 NR5A1 FOXL2
17 adrenal cortical hypofunction 9.9 NR5A1 NR0B1
18 benign struma ovarii 9.9 WT1 PTCH1
19 larsen-like syndrome b3gat3 type 9.9 TRIM8 MAF
20 tumoral calcinosis, hyperphosphatemic, familial, 1 9.9 PTCH1 IHH HHAT
21 ciliary dyskinesia, primary, 8 9.9 TRIM8 MAF
22 denys-drash syndrome 9.9 WT1 NR5A1 NR0B1
23 ciliary dyskinesia, primary, 4 9.9 TRIM8 MAF
24 basal cell nevus syndrome 9.9 PTCH1 IHH HHAT
25 mixed gonadal dysgenesis 9.9 SOX9 NR5A1 FOXL2
26 blepharophimosis, ptosis, and epicanthus inversus 9.9 SOX9 NR5A1 FOXL2
27 campomelic dysplasia 9.9 SOX9 NR5A1 FOXL2
28 46,xx sex reversal 1 9.9 SOX9 NR5A1 NR0B1
29 nephrogenic adenofibroma 9.8 WT1 MAF
30 46 xx gonadal dysgenesis 9.8 NR5A1 FOXL2
31 nonsyndromic disorders of testicular development 9.8 WNT4 NR5A1 NR0B1 MAP3K1
32 cartilage disease 9.8 SOX9 IHH
33 46,xy sex reversal 9 9.8 WT1 SOX9 NR5A1
34 frasier syndrome 9.8 WT1 SOX9 NR5A1
35 craniopharyngioma 9.7 SOX9 PTCH1 NR5A1
36 hypospadias 9.7 WT1 SOX9 NR5A1
37 hermaphroditism 9.7 WNT4 SOX9 NR0B1 FOXL2
38 adrenal hypoplasia, congenital 9.7 WNT4 SOX9 NR5A1 NR0B1
39 chromosome 2q35 duplication syndrome 9.6 SOX9 PTCH1 IHH
40 cryptorchidism, unilateral or bilateral 9.6 WT1 SOX9 NR5A1 NR0B1
41 ovarian gonadoblastoma 9.6 WT1 WNT4 SOX9 NR0B1
42 46,xx sex reversal 9.5 WNT4 SOX9 NR5A1 NR0B1 FOXL2
43 wilms tumor 1 9.5 WT1 SOX9 NR5A1 NR0B1
44 gonadoblastoma 9.4 WT1 SOX9 NR5A1 NR0B1 FOXL2
45 46,xy partial gonadal dysgenesis 9.4 WT1 SOX9 NR5A1 NR0B1 MAP3K1
46 persistent mullerian duct syndrome 9.4 WT1 WNT4 SOX9 NR5A1 NR0B1
47 aniridia 1 9.3 WT1 SOX9 NR5A1 MAF
48 pseudohermaphroditism 9.3 WT1 WNT4 SOX9 NR5A1 NR0B1 HHAT
49 gonadal dysgenesis 9.3 WT1 SOX9 NR5A1 NR0B1 MAP3K1 FOXL2
50 46,xy sex reversal 2 9.2 WT1 WNT4 SOX9 NR5A1 NR0B1 FOXL2

Graphical network of the top 20 diseases related to Nivelon-Nivelon-Mabille Syndrome:



Diseases related to Nivelon-Nivelon-Mabille Syndrome

Symptoms & Phenotypes for Nivelon-Nivelon-Mabille Syndrome

Human phenotypes related to Nivelon-Nivelon-Mabille Syndrome:

58 31 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 macrotia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000400
3 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
4 intrauterine growth retardation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001511
5 telecanthus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000506
6 abnormality of pelvic girdle bone morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0002644
7 narrow chest 58 31 hallmark (90%) Very frequent (99-80%) HP:0000774
8 micromelia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002983
9 short metacarpal 58 31 hallmark (90%) Very frequent (99-80%) HP:0010049
10 severe short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0003510
11 increased skull ossification 58 31 hallmark (90%) Very frequent (99-80%) HP:0004330
12 broad long bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0005622
13 short phalanx of finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0009803
14 abnormal shoulder morphology 31 hallmark (90%) HP:0003043
15 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
16 hypoplasia of the iris 58 31 frequent (33%) Frequent (79-30%) HP:0007676
17 chorioretinal coloboma 58 31 frequent (33%) Frequent (79-30%) HP:0000567
18 deeply set eye 58 31 frequent (33%) Frequent (79-30%) HP:0000490
19 blepharophimosis 58 31 frequent (33%) Frequent (79-30%) HP:0000581
20 male pseudohermaphroditism 58 31 frequent (33%) Frequent (79-30%) HP:0000037
21 miosis 58 31 frequent (33%) Frequent (79-30%) HP:0000616
22 cerebral hypoplasia 31 frequent (33%) HP:0006872
23 abnormality of the shoulder 58 Very frequent (99-80%)
24 cerebellar vermis hypoplasia 31 HP:0001320
25 brain very small 58 Frequent (79-30%)
26 coloboma 31 HP:0000589
27 bell-shaped thorax 31 HP:0001591
28 abnormal clavicle morphology 31 HP:0000889
29 trapezoidal shaped vertebral bodies 31 HP:0005621

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Head:
microcephaly

Neurologic Central Nervous System:
cerebellar vermis hypoplasia

Head And Neck Eyes:
iris hypoplasia
optic disc coloboma

Growth Height:
dwarfism, severe antenatal

Genitourinary External Genitalia Female:
normal female genitalia

Skeletal:
chondrodysplasia

Laboratory Abnormalities:
46,xy karyotype (1 of 2 patients)

Skeletal Limbs:
micromelia

Skeletal Hands:
short metacarpals
short phalanges

Chest External Features:
narrow thorax

Chest Ribs Sternum Clavicles And Scapulae:
abnormal clavicles

Genitourinary Internal Genitalia Female:
normal female genitalia

Skeletal Spine:
trapezoid-shaped vertebral bodies

Clinical features from OMIM®:

600092 (Updated 05-Mar-2021)

MGI Mouse Phenotypes related to Nivelon-Nivelon-Mabille Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.15 FOXL2 HHAT IHH MAF MAP3K1 NR5A1
2 endocrine/exocrine gland MP:0005379 10.06 FOXL2 HHAT IHH NR0B1 NR5A1 PTCH1
3 homeostasis/metabolism MP:0005376 10.06 FOXL2 HHAT MAF MAP3K1 NR0B1 NR5A1
4 embryo MP:0005380 10.03 HHAT IHH MAF NR5A1 PTCH1 SOX9
5 limbs/digits/tail MP:0005371 9.73 HHAT IHH MAF PTCH1 SOX9 WNT4
6 no phenotypic analysis MP:0003012 9.63 FOXL2 IHH PTCH1 SOX9 WNT4 WT1
7 reproductive system MP:0005389 9.56 FOXL2 HHAT NR0B1 NR5A1 PTCH1 SOX9
8 skeleton MP:0005390 9.23 HHAT IHH MAP3K1 NR0B1 PTCH1 SOX9

Drugs & Therapeutics for Nivelon-Nivelon-Mabille Syndrome

Search Clinical Trials , NIH Clinical Center for Nivelon-Nivelon-Mabille Syndrome

Cochrane evidence based reviews: nivelon nivelon mabille syndrome

Genetic Tests for Nivelon-Nivelon-Mabille Syndrome

Anatomical Context for Nivelon-Nivelon-Mabille Syndrome

MalaCards organs/tissues related to Nivelon-Nivelon-Mabille Syndrome:

40
Eye, Bone, Brain

Publications for Nivelon-Nivelon-Mabille Syndrome

Articles related to Nivelon-Nivelon-Mabille Syndrome:

# Title Authors PMID Year
1
Biallelic novel missense HHAT variant causes syndromic microcephaly and cerebellar-vermis hypoplasia. 57 6 61
30912300 2019
2
Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmitoylation and signaling. 6 57
24784881 2014
3
Unique survival in chrondrodysplasia-hermaphrodism syndrome. 57
15578577 2005
4
New autosomal recessive chondrodysplasia--pseudohermaphrodism syndrome. 57
1342874 1992

Variations for Nivelon-Nivelon-Mabille Syndrome

ClinVar genetic disease variations for Nivelon-Nivelon-Mabille Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HHAT NM_018194.6(HHAT):c.860G>T (p.Gly287Val) SNV Pathogenic 987946 1:210637852-210637852 1:210464508-210464508
2 HHAT NM_018194.6(HHAT):c.770T>C (p.Leu257Pro) SNV Pathogenic 987947 1:210591583-210591583 1:210418239-210418239

Expression for Nivelon-Nivelon-Mabille Syndrome

Search GEO for disease gene expression data for Nivelon-Nivelon-Mabille Syndrome.

Pathways for Nivelon-Nivelon-Mabille Syndrome

Pathways related to Nivelon-Nivelon-Mabille Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.14 SOX9 PTCH1 IHH
2 10.88 PTCH1 IHH HHAT
3
Show member pathways
10.54 PTCH1 IHH
4
Show member pathways
10.28 PTCH1 IHH HHAT

GO Terms for Nivelon-Nivelon-Mabille Syndrome

Cellular components related to Nivelon-Nivelon-Mabille Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 9.1 WT1 SOX9 NR5A1 NR0B1 MAF FOXL2

Biological processes related to Nivelon-Nivelon-Mabille Syndrome according to GeneCards Suite gene sharing:

(show all 26)
# Name GO ID Score Top Affiliating Genes
1 cell differentiation GO:0030154 10.04 WNT4 SOX9 NR5A1 NR0B1 IHH FOXL2
2 negative regulation of transcription by RNA polymerase II GO:0000122 10.01 WWC3 WT1 SOX9 PTCH1 NR0B1 MAF
3 positive regulation of transcription, DNA-templated GO:0045893 9.95 WT1 WNT4 TRIM8 SOX9 PTCH1 NR5A1
4 negative regulation of transcription, DNA-templated GO:0045892 9.91 WT1 WNT4 SOX9 PTCH1 NR0B1 FOXL2
5 transcription initiation from RNA polymerase II promoter GO:0006367 9.8 SOX9 NR5A1 NR0B1
6 smoothened signaling pathway GO:0007224 9.72 PTCH1 IHH HHAT
7 positive regulation of collagen biosynthetic process GO:0032967 9.62 WNT4 IHH
8 female gonad development GO:0008585 9.62 WNT4 NR5A1
9 positive regulation of mesenchymal cell proliferation GO:0002053 9.61 SOX9 IHH
10 somite development GO:0061053 9.61 PTCH1 IHH
11 hormone metabolic process GO:0042445 9.6 WNT4 NR5A1
12 prostate gland development GO:0030850 9.59 SOX9 PTCH1
13 gonad development GO:0008406 9.58 WT1 NR0B1
14 smooth muscle tissue development GO:0048745 9.58 PTCH1 IHH
15 mesenchymal to epithelial transition GO:0060231 9.56 WT1 WNT4
16 male sex determination GO:0030238 9.54 SOX9 NR5A1 NR0B1
17 Sertoli cell differentiation GO:0060008 9.52 SOX9 NR0B1
18 negative regulation of steroid biosynthetic process GO:0010894 9.51 WNT4 NR0B1
19 positive regulation of male gonad development GO:2000020 9.5 WT1 SOX9 NR5A1
20 chondrocyte differentiation involved in endochondral bone morphogenesis GO:0003413 9.49 SOX9 IHH
21 negative regulation of female gonad development GO:2000195 9.48 WT1 NR5A1
22 renal vesicle induction GO:0072034 9.46 WNT4 SOX9
23 branching involved in ureteric bud morphogenesis GO:0001658 9.46 WT1 WNT4 SOX9 PTCH1
24 sex determination GO:0007530 9.43 WT1 NR5A1 NR0B1
25 male gonad development GO:0008584 9.35 WT1 WNT4 SOX9 NR5A1 NR0B1
26 adrenal gland development GO:0030325 8.92 WT1 WNT4 NR5A1 NR0B1

Molecular functions related to Nivelon-Nivelon-Mabille Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity GO:0003700 9.55 WT1 SOX9 NR5A1 MAF FOXL2
2 sequence-specific DNA binding GO:0043565 9.02 WT1 SOX9 NR5A1 MAF FOXL2
3 patched binding GO:0005113 8.96 PTCH1 IHH

Sources for Nivelon-Nivelon-Mabille Syndrome

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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