PVHH
MCID: PRL023
MIFTS: 48

Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome (PVHH)

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

Aliases & Classifications for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

MalaCards integrated aliases for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome:

Name: Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome 57 12 72 36 29 6 15
Encephaloclastic Proliferative Vasculopathy 57 12 58 72 44 70
Hydrocephaly/hydranencephaly Due to Cerebral Vasculopathy 57 12 58 72
Fowler Syndrome 57 12 72 70
Cerebral Proliferative Glomeruloid Vasculopathy 12 58 72
Pvhh 57 12 72
Epv 57 12 72
Proliferative Vasculopathy and Hydranencephaly/hydrocephaly 12 58
Fowler Christmas Chapple Syndrome 20 70
Hydranencephaly, Fowler Type 57 12
Fowler's Syndrome 73 20
Polycystic Ovaries-Urethral Sphincter Dysfunction Syndrome 29
Polycystic Ovaries Urethral Sphincter Dysfunction 20
Encephaloclastic Proliferative Vasculopathy; Epv 57
Voiding Dysfunction and Polycystic Ovaries 20
Hydranencephaly Fowler Type 72
Fowler Vasculopathy 12
Fowler Vasculopaty 58
Pgv 72

Characteristics:

Orphanet epidemiological data:

58
fowler vasculopaty
Inheritance: Autosomal recessive;

OMIM®:

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

Miscellaneous:
stillborn or neonatal death
diagnosis occurs between 23 and 33 weeks' gestation
variable clinical presentation
affected individuals may rarely survive


HPO:

31
proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0111666
OMIM® 57 225790
KEGG 36 H01120
SNOMED-CT 67 700242002
UMLS via Orphanet 71 C1856972 C3203738
Orphanet 58 ORPHA221126
MedGen 41 C1856972
UMLS 70 C1856972 C2931462 C3203738

Summaries for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

GARD : 20 Fowler's syndrome mainly affects young women and leads to the inability to empty the bladder ( urinary retention ). Many women have no other symptoms, although some women experience stomach pain. Fowler's syndrome is caused by spasms of the external urethral sphincter, a band of muscle that opens and closes at the exit of the bladder. The cause is unknown, but it has been known to occur after a surgical procedure, childbirth, opiate use, or other medical condition. Fowler's syndrome is difficult to diagnose, but many women with Fowler's syndrome have abnormal electrical activity on a specialized test called concentric needle electromyography. Fowler's syndrome is most often treated by using a device placed inside the body that helps stimulate the bladder.

MalaCards based summary : Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome, also known as encephaloclastic proliferative vasculopathy, is related to hydranencephaly and hydrocephalus, congenital, 1. An important gene associated with Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome is FLVCR2 (FLVCR Heme Transporter 2), and among its related pathways/superpathways are Biosynthesis of cofactors and Porphyrin and chlorophyll metabolism. The drugs Acetylcholine and abobotulinumtoxinA have been mentioned in the context of this disorder. Affiliated tissues include spinal cord, retina and brain, and related phenotypes are agenesis of corpus callosum and hydrocephalus

Disease Ontology : 12 A syndrome characterized by hydranencephaly, glomeruloid vasculopathy of the central nervous system and retinal vessels, diffuse clastic ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications, and fetal akinesia with arthrogryposis that has material basis in homozygous or compound heterozygous mutation in FLVCR2 on chromosome 14q24.3.

OMIM® : 57 The proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome is a rare, autosomal recessive, usually prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. It is usually diagnosed by ultrasound between 26 and 33 weeks' gestation (summary by Meyer et al., 2010). Rarely, affected individuals may survive, but are severely impaired with almost no neurologic development (Kvarnung et al., 2016). (225790) (Updated 05-Apr-2021)

KEGG : 36 Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as Fowler syndrome, is an autosomal-recessively inherited prenatal lethal disorder of brain angiogenesis, resulting in abnormally thickened and aberrant perforating vessels leading to hydranencephaly. Mutations and a large deletion in the FLVCR2 gene have been revealed in the families with Fowler syndrome. FLVCR2 encodes a transmembrane transporter of the major facilitator superfamily (MFS) hypothesized to be involved in regulation of growth, calcium exchange, and homeostasis.

UniProtKB/Swiss-Prot : 72 Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome: A rare prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. Hydranencephaly is a condition where the greater portions of the cerebral hemispheres and corpus striatum are replaced by cerebrospinal fluid and glial tissue.

Wikipedia : 73 Fowler's syndrome (urethral sphincter relaxation disorder) is a rare disorder in which the urethral... more...

Related Diseases for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

Diseases related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
# Related Disease Score Top Affiliating Genes
1 hydranencephaly 30.8 SLC49A3 LOC102724153 FLVCR2 FLVCR1
2 hydrocephalus, congenital, 1 10.5
3 fowler urethral sphincter dysfunction syndrome 10.5
4 fetal akinesia deformation sequence 1 10.3
5 autosomal recessive disease 10.3
6 polycystic ovary syndrome 10.2
7 acute cystitis 10.2
8 posterior column ataxia 10.2 LOC102724153 FLVCR2 FLVCR1
9 hydrocephalus 10.1
10 cystic lymphangioma 10.1
11 erythrasma 10.1 PPOX CPOX
12 congenital amyoplasia 10.1
13 neuropathy, hereditary sensory and autonomic, type viii 10.0 FLVCR1 ALAS1
14 breast cancer 9.9
15 duodenal ulcer 9.9
16 breast adenocarcinoma 9.9
17 cardiomyopathy, familial hypertrophic, 2 9.9
18 pain agnosia 9.9
19 urinary tract infection 9.9
20 cystitis 9.9
21 endometriosis 9.9
22 ovarian cyst 9.9
23 infertility 9.9
24 chronic pain 9.9
25 dysautonomia 9.9
26 cleft palate, isolated 9.9
27 hypertelorism 9.9
28 multiple pterygium syndrome, escobar variant 9.9
29 microcephaly 9.9
30 aceruloplasminemia 9.9 SLC25A37 HPX FLVCR1
31 photoparoxysmal response 1 9.7 PPOX FECH
32 anemia, sideroblastic, and spinocerebellar ataxia 9.7 SLC25A38 SLC25A37 FECH
33 folate malabsorption, hereditary 9.6 SLC48A1 SLC25A38 SLC25A37 HEBP1 FLVCR2 FLVCR1
34 sideroblastic anemia 9.6 SLC25A38 FECH ALAS1
35 porphyria, congenital erythropoietic 9.5 FECH CPOX ALAD
36 coproporphyria, hereditary 9.1 PPOX FLVCR2 FECH CPOX ALAS1 ALAD
37 variegate porphyria 9.1 PPOX FLVCR2 FECH CPOX ALAS1 ALAD
38 porphyria 9.0 PPOX HPX FECH CPOX ALAS1 ALAD
39 acute porphyria 9.0 SLC25A37 PPOX FECH CPOX ALAS1 ALAD
40 porphyria cutanea tarda 9.0 PPOX HPX FECH CPOX ALAS1 ALAD
41 cutaneous porphyria 9.0 SLC25A37 PPOX FLVCR1 FECH CPOX ALAS1
42 porphyria, acute intermittent 8.8 PPOX HPX FLVCR2 FLVCR1 FECH CPOX
43 anemia, sideroblastic, 1 8.7 SLC25A38 SLC25A37 SLC25A28 FLVCR1 FECH ALAS1
44 protoporphyria, erythropoietic, 1 8.5 SLC25A38 SLC25A37 SLC25A28 PPOX FECH CPOX
45 deficiency anemia 8.2 SLC48A1 SLC25A38 SLC25A37 SLC25A28 PPOX HPX

Graphical network of the top 20 diseases related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome:



Diseases related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome

Symptoms & Phenotypes for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

Human phenotypes related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 agenesis of corpus callosum 31 HP:0001274
2 hydrocephalus 31 HP:0000238
3 global developmental delay 31 HP:0001263
4 microcephaly 31 HP:0000252
5 flexion contracture 31 HP:0001371
6 intrauterine growth retardation 31 HP:0001511
7 micrognathia 31 HP:0000347
8 polyhydramnios 31 HP:0001561
9 dandy-walker malformation 31 HP:0001305
10 premature birth 31 HP:0001622
11 cerebellar hypoplasia 31 HP:0001321
12 abnormality of metabolism/homeostasis 31 HP:0001939
13 hydranencephaly 31 HP:0002324
14 akinesia 31 HP:0002304
15 hypoplasia of the brainstem 31 HP:0002365
16 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
dandy-walker malformation
ventriculomegaly
cerebellar hypoplasia
hydranencephaly
more
Head And Neck Face:
micrognathia

Prenatal Manifestations Delivery:
premature delivery

Prenatal Manifestations:
prenatal diagnosis by ultrasound

Head And Neck Eyes:
glomeruloid vascular proliferation in the retina central visual impairment

Head And Neck Head:
microcephaly

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skeletal:
joint contractures
fetal akinesia deformation sequence
limb deformities

Growth Other:
intrauterine growth retardation (iugr)

Muscle Soft Tissue:
muscular atrophy, neurogenic

Clinical features from OMIM®:

225790 (Updated 05-Apr-2021)

Drugs & Therapeutics for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

Drugs for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved, Investigational Phase 2, Phase 3 51-84-3 187
2 abobotulinumtoxinA Phase 2, Phase 3
3 incobotulinumtoxinA Phase 2, Phase 3
4 Neurotransmitter Agents Phase 2, Phase 3
5 Cholinergic Agents Phase 2, Phase 3
6 Botulinum Toxins Phase 2, Phase 3
7 Botulinum Toxins, Type A Phase 2, Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Open Label Pilot Study to Treat Women With Chronic Urinary Retention or Voiding Dysfunction Due to a Primary Disorder of Sphincter Relaxation (Fowler's Syndrome) With Outpatient Urethral Injections of Botulinum Toxin A (BoNT-A) Completed NCT02428881 Phase 2, Phase 3 onabotulinumtoxinA

Search NIH Clinical Center for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome

Cochrane evidence based reviews: encephaloclastic proliferative vasculopathy

Genetic Tests for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

Genetic tests related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome:

# Genetic test Affiliating Genes
1 Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome 29 FLVCR2
2 Polycystic Ovaries-Urethral Sphincter Dysfunction Syndrome 29

Anatomical Context for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

MalaCards organs/tissues related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome:

40
Spinal Cord, Retina, Brain, Cerebellum, Endothelial

Publications for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

Articles related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome:

(show all 11)
# Title Authors PMID Year
1
Mutations in FLVCR2 associated with Fowler syndrome and survival beyond infancy. 57 6 61
25677735 2016
2
Mutations in FLVCR2 are associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome). 61 6 57
20206334 2010
3
High-throughput sequencing of a 4.1 Mb linkage interval reveals FLVCR2 deletions and mutations in lethal cerebral vasculopathy. 57 6
20690116 2010
4
Unexpected allelic heterogeneity and spectrum of mutations in Fowler syndrome revealed by next-generation exome sequencing. 57 6
20518025 2010
5
Refining the clinicopathological pattern of cerebral proliferative glomeruloid vasculopathy (Fowler syndrome): report of 16 fetal cases. 61 57
19635601 2009
6
Fowler syndrome-a clinical, radiological, and pathological study of 14 cases. 57
20014121 2010
7
Two siblings with early onset fetal akinesia deformation sequence and hydranencephaly: further evidence for autosomal recessive inheritance of hydranencephaly, fowler type. 57
11857548 2002
8
Proliferative vasculopathy and an hydranencephalic-hydrocephalic syndrome: a neuropathological study of two siblings. 57
6852387 1983
9
Congenital hydrocephalus-hydrencephaly in five siblings, with autopsy studies: a new disease. 57
4555262 1972
10
Expanding the clinical spectrum of Fowler syndrome: Three siblings with survival into adulthood and systematic review of the literature. 61
32333401 2020
11
Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism. 61
29500860 2018

Variations for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

ClinVar genetic disease variations for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome:

6 (show all 18)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FLVCR2 NM_017791.3(FLVCR2):c.1289C>G (p.Thr430Arg) SNV Pathogenic 1087 rs267606825 GRCh37: 14:76107351-76107351
GRCh38: 14:75641008-75641008
2 FLVCR2 NM_017791.3(FLVCR2):c.1192C>G (p.Leu398Val) SNV Pathogenic 1089 rs267606822 GRCh37: 14:76105762-76105762
GRCh38: 14:75639419-75639419
3 FLVCR2 , LOC102724153 NM_017791.3(FLVCR2):c.473C>A (p.Ser158Ter) SNV Pathogenic 1090 rs138495705 GRCh37: 14:76045788-76045788
GRCh38: 14:75579445-75579445
4 FLVCR2 NM_017791.3(FLVCR2):c.977C>T (p.Ala326Val) SNV Pathogenic 1092 rs267606824 GRCh37: 14:76099996-76099996
GRCh38: 14:75633653-75633653
5 FLVCR2 NM_017791.3(FLVCR2):c.1341+2T>C SNV Pathogenic 1093 rs780523767 GRCh37: 14:76107405-76107405
GRCh38: 14:75641062-75641062
6 FLVCR2 , LOC102724153 NM_017791.3(FLVCR2):c.402C>G (p.Tyr134Ter) SNV Pathogenic 30856 rs759296326 GRCh37: 14:76045717-76045717
GRCh38: 14:75579374-75579374
7 FLVCR2 NM_017791.3(FLVCR2):c.1289C>T (p.Thr430Met) SNV Pathogenic 523100 rs267606825 GRCh37: 14:76107351-76107351
GRCh38: 14:75641008-75641008
8 FLVCR2 , LOC102724153 NM_017791.2(FLVCR2):c.329_334delACATCT (p.Asn110_Phe112delinsIle) Deletion Pathogenic 1088 rs746459536 GRCh37: 14:76045644-76045649
GRCh38: 14:75579301-75579306
9 FLVCR2 NM_017791.3(FLVCR2):c.839C>G (p.Pro280Arg) SNV Pathogenic 1091 rs267606823 GRCh37: 14:76090982-76090982
GRCh38: 14:75624639-75624639
10 FLVCR2 NM_017791.3(FLVCR2):c.733G>T (p.Glu245Ter) SNV Pathogenic 1032767 GRCh37: 14:76088485-76088485
GRCh38: 14:75622142-75622142
11 FLVCR2 , LOC102724153 NM_017791.3(FLVCR2):c.391dup (p.Met131fs) Duplication Likely pathogenic 667372 rs1594785775 GRCh37: 14:76045705-76045706
GRCh38: 14:75579362-75579363
12 FLVCR2 NM_017791.3(FLVCR2):c.1019C>T (p.Pro340Leu) SNV Uncertain significance 1032766 GRCh37: 14:76100038-76100038
GRCh38: 14:75633695-75633695
13 FLVCR2 NM_017791.3(FLVCR2):c.*1411_*1412del Deletion Uncertain significance 314432 rs764857255 GRCh37: 14:76114226-76114227
GRCh38: 14:75647883-75647884
14 FLVCR2 NM_017791.3(FLVCR2):c.*734del Deletion Uncertain significance 314427 rs538801836 GRCh37: 14:76113549-76113549
GRCh38: 14:75647206-75647206
15 FLVCR2 NM_017791.3(FLVCR2):c.*1085T>G SNV Uncertain significance 314430 rs886050790 GRCh37: 14:76113900-76113900
GRCh38: 14:75647557-75647557
16 FLVCR2 NM_017791.3(FLVCR2):c.*1413_*1414GT[9] Microsatellite Uncertain significance 314433 rs138622317 GRCh37: 14:76114226-76114227
GRCh38: 14:75647883-75647884
17 FLVCR2 , LOC102724153 NM_017791.3(FLVCR2):c.-121_-120CT[1] Microsatellite Benign 314404 rs1322268460 GRCh37: 14:76045194-76045195
GRCh38: 14:75578851-75578852
18 FLVCR2 , LOC102724153 NM_017791.2(FLVCR2):c.-356G>C SNV Benign 314403 rs3813550 GRCh37: 14:76044960-76044960
GRCh38: 14:75578617-75578617

UniProtKB/Swiss-Prot genetic disease variations for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 FLVCR2 p.Pro280Arg VAR_064043 rs267606823
2 FLVCR2 p.Leu398Val VAR_064044 rs267606822
3 FLVCR2 p.Thr430Arg VAR_064045 rs267606825
4 FLVCR2 p.Arg84His VAR_064410
5 FLVCR2 p.Ala326Val VAR_064412 rs267606824
6 FLVCR2 p.Thr352Arg VAR_064413
7 FLVCR2 p.Gly412Arg VAR_064414
8 FLVCR2 p.Thr430Met VAR_064415 rs267606825

Expression for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

Search GEO for disease gene expression data for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome.

Pathways for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

GO Terms for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

Cellular components related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.35 SLC25A38 SLC25A37 SLC25A28 PPOX FECH
2 mitochondrion GO:0005739 9.28 SLC25A38 SLC25A37 SLC25A28 PPOX PET117 FLVCR1

Biological processes related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 iron ion homeostasis GO:0055072 9.54 SLC25A37 SLC25A28
2 response to lead ion GO:0010288 9.52 FECH ALAD
3 response to metal ion GO:0010038 9.51 FECH ALAD
4 response to arsenic-containing substance GO:0046685 9.49 FECH ALAD
5 response to methylmercury GO:0051597 9.48 FECH ALAD
6 tetrapyrrole biosynthetic process GO:0033014 9.46 ALAS1 ALAD
7 porphyrin-containing compound biosynthetic process GO:0006779 9.46 PPOX FECH CPOX ALAD
8 heme export GO:0097037 9.43 FLVCR2 FLVCR1
9 heme transport GO:0015886 9.43 SLC48A1 HPX FLVCR1
10 response to platinum ion GO:0070541 9.4 FECH ALAD
11 protoporphyrinogen IX metabolic process GO:0046501 9.37 PPOX FECH
12 iron import into the mitochondrion GO:0048250 9.32 SLC25A37 SLC25A28
13 protoporphyrinogen IX biosynthetic process GO:0006782 9.26 PPOX CPOX ALAS1 ALAD
14 heme biosynthetic process GO:0006783 9.1 SLC25A38 PPOX FECH CPOX ALAS1 ALAD

Molecular functions related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 heme binding GO:0020037 9.26 SLC48A1 HEBP1 FLVCR2 FLVCR1
2 iron ion transmembrane transporter activity GO:0005381 9.16 SLC25A37 SLC25A28
3 heme transporter activity GO:0015232 8.92 SLC48A1 HPX FLVCR2 FLVCR1

Sources for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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