PVHH
MCID: PRL023
MIFTS: 44

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 56 12 73 36 29 6 15
Encephaloclastic Proliferative Vasculopathy 56 12 58 73 43 71
Hydrocephaly/hydranencephaly Due to Cerebral Vasculopathy 56 12 58 73
Fowler Syndrome 56 12 73 71
Cerebral Proliferative Glomeruloid Vasculopathy 12 58 73
Pvhh 56 12 73
Epv 56 12 73
Proliferative Vasculopathy and Hydranencephaly/hydrocephaly 12 58
Fowler Christmas Chapple Syndrome 52 71
Hydranencephaly, Fowler Type 56 12
Fowler's Syndrome 74 52
Polycystic Ovaries Urethral Sphincter Dysfunction 52
Encephaloclastic Proliferative Vasculopathy; Epv 56
Voiding Dysfunction and Polycystic Ovaries 52
Hydranencephaly Fowler Type 73
Fowler Vasculopathy 12
Fowler Vasculopaty 58
Pgv 73

Characteristics:

Orphanet epidemiological data:

58
fowler vasculopaty
Inheritance: Autosomal recessive;

OMIM:

56
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 56 225790
KEGG 36 H01120
SNOMED-CT 67 700242002
UMLS via Orphanet 72 C1856972 C3203738
Orphanet 58 ORPHA221126
MedGen 41 C1856972
UMLS 71 C1856972 C2931462 C3203738

Summaries for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

OMIM : 56 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)

MalaCards based summary : Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome, also known as encephaloclastic proliferative vasculopathy, is related to hydranencephaly and fowler urethral sphincter dysfunction syndrome. An important gene associated with Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome is FLVCR2 (FLVCR Heme Transporter 2). The drugs Acetylcholine and abobotulinumtoxinA have been mentioned in the context of this disorder. Affiliated tissues include brain, ovary and spinal cord, and related phenotypes are global developmental delay 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.

NIH Rare Diseases : 52 Fowler's syndrome is characterized by urinary retention associated with abnormal electromyographic activity in young women in the absence of overt neurologic disease. Some women with this syndrome have polycystic ovaries as well.

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 : 73 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 : 74 Fowler's syndrome (Non neurogenic urinary retention) is a disease characterized by urinary retention... 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 38)
# Related Disease Score Top Affiliating Genes
1 hydranencephaly 30.7 SLC49A3 LOC102724153 FLVCR2 FLVCR1
2 fowler urethral sphincter dysfunction syndrome 10.5
3 fetal akinesia deformation sequence 1 10.4
4 autosomal recessive disease 10.4
5 duodenal ulcer 10.3
6 vaccinia 10.3
7 polycystic ovary syndrome 10.2
8 hydrocephalus, congenital, 1 10.2
9 hydrocephalus 10.2
10 cystic lymphangioma 10.2
11 acute cystitis 10.2
12 partial cryptophthalmia 10.1 FLVCR2 DCT
13 alkuraya-kucinskas syndrome 10.1
14 congenital amyoplasia 10.1
15 congenital symblepharon 10.1 FLVCR2 DCT
16 posterior column ataxia 10.1 LOC102724153 FLVCR2 FLVCR1
17 fraser syndrome 2 10.1 FLVCR2 DCT
18 cryptophthalmos, unilateral or bilateral, isolated 10.0 FLVCR2 DCT
19 cardiomyopathy, familial hypertrophic, 2 10.0
20 pain agnosia 10.0
21 cystitis 10.0
22 endometriosis 10.0
23 ovarian cyst 10.0
24 infertility 10.0
25 chronic pain 10.0
26 dysautonomia 10.0
27 cleft palate, isolated 10.0
28 hypertelorism 10.0
29 dandy-walker syndrome 10.0
30 multiple pterygium syndrome, escobar variant 10.0
31 microcephaly 10.0
32 neuropathy, hereditary sensory and autonomic, type viii 9.7 FLVCR1 ALAS1
33 coproporphyria, hereditary 9.6 FLVCR1 CPOX ALAS1
34 porphyria, acute intermittent 9.6 FLVCR1 CPOX ALAS1
35 protoporphyria, erythropoietic, 1 9.4 SLC25A37 CPOX ALAS1
36 acute porphyria 9.4 SLC25A37 CPOX ALAS1
37 variegate porphyria 9.4 CPOX ALAS1
38 cutaneous porphyria 9.3 SLC25A37 FLVCR1 CPOX ALAS1

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 global developmental delay 31 HP:0001263
2 hydrocephalus 31 HP:0000238
3 microcephaly 31 HP:0000252
4 flexion contracture 31 HP:0001371
5 abnormality of metabolism/homeostasis 31 HP:0001939
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 agenesis of corpus callosum 31 HP:0001274
11 premature birth 31 HP:0001622
12 cerebellar hypoplasia 31 HP:0001321
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:

56
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

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 Cholinergic Agents Phase 2, Phase 3
4 incobotulinumtoxinA Phase 2, Phase 3
5 Botulinum Toxins Phase 2, Phase 3
6 Botulinum Toxins, Type A Phase 2, Phase 3
7 Neurotransmitter Agents 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
2 Clinical and Molecular Characterization of Cerebral Proliferative Vasculopathy Completed NCT03293134
3 Case Control Study to Investigate the Use of Urethral Pressure Profile Measurement in Children Not yet recruiting NCT04147793

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

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

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

40
Brain, Ovary, Spinal Cord, Retina, 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. 61 6 56
25677735 2016
2
Mutations in FLVCR2 are associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome). 61 56 6
20206334 2010
3
Refining the clinicopathological pattern of cerebral proliferative glomeruloid vasculopathy (Fowler syndrome): report of 16 fetal cases. 61 6 56
19635601 2009
4
High-throughput sequencing of a 4.1 Mb linkage interval reveals FLVCR2 deletions and mutations in lethal cerebral vasculopathy. 56 6
20690116 2010
5
Unexpected allelic heterogeneity and spectrum of mutations in Fowler syndrome revealed by next-generation exome sequencing. 6 56
20518025 2010
6
Fowler syndrome-a clinical, radiological, and pathological study of 14 cases. 56
20014121 2010
7
Two siblings with early onset fetal akinesia deformation sequence and hydranencephaly: further evidence for autosomal recessive inheritance of hydranencephaly, fowler type. 56
11857548 2002
8
Proliferative vasculopathy and an hydranencephalic-hydrocephalic syndrome: a neuropathological study of two siblings. 56
6852387 1983
9
Congenital hydrocephalus-hydrencephaly in five siblings, with autopsy studies: a new disease. 56
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 16) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FLVCR2 NM_017791.3(FLVCR2):c.1289C>T (p.Thr430Met)SNV Pathogenic 523100 rs267606825 14:76107351-76107351 14:75641008-75641008
2 FLVCR2 NM_017791.3(FLVCR2):c.1289C>G (p.Thr430Arg)SNV Pathogenic 1087 rs267606825 14:76107351-76107351 14:75641008-75641008
3 FLVCR2 NM_017791.3(FLVCR2):c.977C>T (p.Ala326Val)SNV Pathogenic 1092 rs267606824 14:76099996-76099996 14:75633653-75633653
4 FLVCR2 NM_017791.3(FLVCR2):c.1341+2T>CSNV Pathogenic 1093 rs780523767 14:76107405-76107405 14:75641062-75641062
5 FLVCR2 NM_017791.3(FLVCR2):c.402C>G (p.Tyr134Ter)SNV Pathogenic 30856 rs759296326 14:76045717-76045717 14:75579374-75579374
6 FLVCR2 NM_017791.3(FLVCR2):c.1192C>G (p.Leu398Val)SNV Pathogenic 1089 rs267606822 14:76105762-76105762 14:75639419-75639419
7 FLVCR2 NM_017791.3(FLVCR2):c.473C>A (p.Ser158Ter)SNV Pathogenic 1090 rs138495705 14:76045788-76045788 14:75579445-75579445
8 FLVCR2 NM_017791.3(FLVCR2):c.391dup (p.Met131fs)duplication Likely pathogenic 667372 14:76045705-76045706 14:75579362-75579363
9 FLVCR2 NM_017791.2(FLVCR2):c.329_334delACATCT (p.Asn110_Phe112delinsIle)deletion Uncertain significance 1088 rs746459536 14:76045644-76045649 14:75579301-75579306
10 FLVCR2 NM_017791.3(FLVCR2):c.*1085T>GSNV Uncertain significance 314430 rs886050790 14:76113900-76113900 14:75647557-75647557
11 FLVCR2 NM_017791.3(FLVCR2):c.*1413_*1414GT[9]short repeat Uncertain significance 314433 rs138622317 14:76114226-76114227 14:75647883-75647884
12 FLVCR2 NM_017791.3(FLVCR2):c.839C>G (p.Pro280Arg)SNV Uncertain significance 1091 rs267606823 14:76090982-76090982 14:75624639-75624639
13 FLVCR2 NM_017791.3(FLVCR2):c.*734deldeletion Uncertain significance 314427 rs538801836 14:76113549-76113549 14:75647206-75647206
14 FLVCR2 NM_017791.3(FLVCR2):c.*1411_*1412deldeletion Uncertain significance 314432 rs764857255 14:76114226-76114227 14:75647883-75647884
15 FLVCR2 NM_017791.2(FLVCR2):c.-356G>CSNV Benign 314403 rs3813550 14:76044960-76044960 14:75578617-75578617
16 FLVCR2 NM_017791.3(FLVCR2):c.-121_-120CT[1]short repeat Benign 314404 rs1322268460 14:76045194-76045195 14:75578851-75578852

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

73
# 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 integral component of membrane GO:0016021 9.32 SLC49A3 SLC48A1 SLC25A37 KCNQ1 GRM1 FLVCR2

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

# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.62 SLC49A3 KCNQ1 FLVCR2 FLVCR1
2 heme biosynthetic process GO:0006783 9.26 CPOX ALAS1
3 protoporphyrinogen IX biosynthetic process GO:0006782 9.16 CPOX ALAS1
4 heme transport GO:0015886 8.96 SLC48A1 FLVCR1
5 heme export GO:0097037 8.62 FLVCR2 FLVCR1

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 9.46 SLC48A1 HEBP1 FLVCR2 FLVCR1
2 heme transporter activity GO:0015232 9.13 SLC48A1 FLVCR2 FLVCR1
3 cofactor transmembrane transporter activity GO:0051184 8.8 SLC49A3 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....