PVHH
MCID: PRL023
MIFTS: 41

Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome (PVHH)

Categories: Cardiovascular diseases, Eye diseases, 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
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
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
Fowler's Syndrome 52
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


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 Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, ovary and spinal cord, and related phenotypes are emg abnormality and polycystic ovaries

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.

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

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 27)
# Description HPO Frequency HPO Source Accession
1 emg abnormality 31 frequent (33%) HP:0003457
2 polycystic ovaries 31 frequent (33%) HP:0000147
3 abnormality of the urethra 31 frequent (33%) HP:0000795
4 dysuria 31 frequent (33%) HP:0100518
5 acne 31 occasional (7.5%) HP:0001061
6 urinary retention 31 occasional (7.5%) HP:0000016
7 oligomenorrhea 31 occasional (7.5%) HP:0000876
8 hirsutism 31 occasional (7.5%) HP:0001007
9 menorrhagia 31 very rare (1%) HP:0000132
10 urinary incontinence 31 very rare (1%) HP:0000020
11 amenorrhea 31 very rare (1%) HP:0000141
12 agenesis of corpus callosum 31 HP:0001274
13 seizures 31 HP:0001250
14 hydrocephalus 31 HP:0000238
15 global developmental delay 31 HP:0001263
16 micrognathia 31 HP:0000347
17 intrauterine growth retardation 31 HP:0001511
18 microcephaly 31 HP:0000252
19 flexion contracture 31 HP:0001371
20 polyhydramnios 31 HP:0001561
21 hypoplasia of the brainstem 31 HP:0002365
22 abnormality of metabolism/homeostasis 31 HP:0001939
23 cerebellar hypoplasia 31 HP:0001321
24 dandy-walker malformation 31 HP:0001305
25 premature birth 31 HP:0001622
26 hydranencephaly 31 HP:0002324
27 akinesia 31 HP:0002304

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
ventriculomegaly
cerebellar hypoplasia
dandy-walker malformation
hydranencephaly
more
Head And Neck Head:
microcephaly

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 Face:
micrognathia

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 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved, Investigational Phase 2, Phase 3 51-84-3 187
2 Neurotransmitter Agents Phase 2, Phase 3
3 incobotulinumtoxinA Phase 2, Phase 3
4 abobotulinumtoxinA Phase 2, Phase 3
5 Acetylcholine Release Inhibitors Phase 2, Phase 3
6 Neuromuscular Agents Phase 2, Phase 3
7 Botulinum Toxins Phase 2, Phase 3
8 Cholinergic Agents Phase 2, Phase 3
9 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
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, Eye

Publications for Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly...

Articles related to Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome:

# Title Authors PMID Year
1
Mutations in FLVCR2 associated with Fowler syndrome and survival beyond infancy. 61 56 6
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 56 6
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. 56 6
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
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 46) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FLVCR2 NM_017791.3(FLVCR2):c.1289C>G (p.Thr430Arg)SNV Pathogenic 1087 rs267606825 14:76107351-76107351 14:75641008-75641008
2 FLVCR2 NM_017791.3(FLVCR2):c.1192C>G (p.Leu398Val)SNV Pathogenic 1089 rs267606822 14:76105762-76105762 14:75639419-75639419
3 FLVCR2 NM_017791.3(FLVCR2):c.473C>A (p.Ser158Ter)SNV Pathogenic 1090 rs138495705 14:76045788-76045788 14:75579445-75579445
4 FLVCR2 NM_017791.3(FLVCR2):c.977C>T (p.Ala326Val)SNV Pathogenic 1092 rs267606824 14:76099996-76099996 14:75633653-75633653
5 FLVCR2 NM_017791.3(FLVCR2):c.1341+2T>CSNV Pathogenic 1093 rs780523767 14:76107405-76107405 14:75641062-75641062
6 FLVCR2 NM_017791.3(FLVCR2):c.402C>G (p.Tyr134Ter)SNV Pathogenic 30856 rs759296326 14:76045717-76045717 14:75579374-75579374
7 FLVCR2 NM_017791.3(FLVCR2):c.1289C>T (p.Thr430Met)SNV Pathogenic 523100 rs267606825 14:76107351-76107351 14:75641008-75641008
8 FLVCR2 NM_017791.3(FLVCR2):c.391dup (p.Met131fs)duplication Likely pathogenic 667372 14:76045705-76045706 14:75579362-75579363
9 FLVCR2 NM_017791.3(FLVCR2):c.*1411_*1412deldeletion Uncertain significance 314432 rs764857255 14:76114226-76114227 14:75647883-75647884
10 FLVCR2 NM_017791.3(FLVCR2):c.839C>G (p.Pro280Arg)SNV Uncertain significance 1091 rs267606823 14:76090982-76090982 14:75624639-75624639
11 FLVCR2 NM_017791.2(FLVCR2):c.329_334delACATCT (p.Asn110_Phe112delinsIle)deletion Uncertain significance 1088 rs746459536 14:76045644-76045649 14:75579301-75579306
12 FLVCR2 NM_017791.3(FLVCR2):c.421G>A (p.Val141Met)SNV Uncertain significance 314412 rs193042691 14:76045736-76045736 14:75579393-75579393
13 FLVCR2 NM_017791.3(FLVCR2):c.953-15C>TSNV Uncertain significance 314416 rs188707531 14:76099957-76099957 14:75633614-75633614
14 FLVCR2 NM_017791.3(FLVCR2):c.*18C>TSNV Uncertain significance 314420 rs369026585 14:76112833-76112833 14:75646490-75646490
15 FLVCR2 NM_017791.3(FLVCR2):c.*573C>TSNV Uncertain significance 314426 rs116699854 14:76113388-76113388 14:75647045-75647045
16 FLVCR2 NM_017791.3(FLVCR2):c.*1085T>GSNV Uncertain significance 314430 rs886050790 14:76113900-76113900 14:75647557-75647557
17 FLVCR2 NM_017791.3(FLVCR2):c.*1413_*1414GT[9]short repeat Uncertain significance 314433 rs138622317 14:76114226-76114227 14:75647883-75647884
18 FLVCR2 NM_017791.3(FLVCR2):c.905C>A (p.Ala302Asp)SNV Uncertain significance 314414 rs183200579 14:76091048-76091048 14:75624705-75624705
19 FLVCR2 NM_017791.3(FLVCR2):c.947C>G (p.Thr316Ser)SNV Uncertain significance 314415 rs779117746 14:76091090-76091090 14:75624747-75624747
20 FLVCR2 NM_017791.3(FLVCR2):c.1326C>T (p.Leu442=)SNV Uncertain significance 314417 rs886050787 14:76107388-76107388 14:75641045-75641045
21 FLVCR2 NM_017791.3(FLVCR2):c.*756A>GSNV Uncertain significance 314428 rs78654241 14:76113571-76113571 14:75647228-75647228
22 FLVCR2 NM_017791.3(FLVCR2):c.*1633A>CSNV Uncertain significance 314435 rs552943781 14:76114448-76114448 14:75648105-75648105
23 FLVCR2 NM_017791.3(FLVCR2):c.1474C>T (p.Arg492Trp)SNV Uncertain significance 314419 rs139495418 14:76108206-76108206 14:75641863-75641863
24 FLVCR2 NM_017791.3(FLVCR2):c.*517C>TSNV Uncertain significance 314425 rs188459017 14:76113332-76113332 14:75646989-75646989
25 FLVCR2 NM_017791.3(FLVCR2):c.*1588A>CSNV Uncertain significance 314434 rs764448107 14:76114403-76114403 14:75648060-75648060
26 FLVCR2 NM_017791.3(FLVCR2):c.-111T>CSNV Uncertain significance 314405 rs80001297 14:76045205-76045205 14:75578862-75578862
27 FLVCR2 NM_017791.3(FLVCR2):c.78C>A (p.Ser26Arg)SNV Uncertain significance 314408 rs768707435 14:76045393-76045393 14:75579050-75579050
28 FLVCR2 NM_017791.3(FLVCR2):c.164C>T (p.Pro55Leu)SNV Uncertain significance 314409 rs372243784 14:76045479-76045479 14:75579136-75579136
29 FLVCR2 NM_017791.3(FLVCR2):c.286A>G (p.Met96Val)SNV Uncertain significance 314410 rs199805789 14:76045601-76045601 14:75579258-75579258
30 FLVCR2 NM_017791.3(FLVCR2):c.604G>A (p.Ala202Thr)SNV Uncertain significance 314413 rs886050786 14:76045919-76045919 14:75579576-75579576
31 FLVCR2 NM_017791.3(FLVCR2):c.*98T>CSNV Uncertain significance 314421 rs886050788 14:76112913-76112913 14:75646570-75646570
32 FLVCR2 NM_017791.3(FLVCR2):c.*155C>TSNV Uncertain significance 314422 rs562468033 14:76112970-76112970 14:75646627-75646627
33 FLVCR2 NM_017791.3(FLVCR2):c.*187T>CSNV Uncertain significance 314423 rs75002047 14:76113002-76113002 14:75646659-75646659
34 FLVCR2 NM_017791.3(FLVCR2):c.*379T>CSNV Uncertain significance 314424 rs886050789 14:76113194-76113194 14:75646851-75646851
35 FLVCR2 NM_017791.3(FLVCR2):c.*734deldeletion Uncertain significance 314427 rs538801836 14:76113549-76113549 14:75647206-75647206
36 FLVCR2 NM_017791.3(FLVCR2):c.*1040C>TSNV Likely benign 314429 rs8017131 14:76113855-76113855 14:75647512-75647512
37 FLVCR2 NM_017791.3(FLVCR2):c.-71C>TSNV Likely benign 314407 rs11849590 14:76045245-76045245 14:75578902-75578902
38 FLVCR2 NM_017791.3(FLVCR2):c.*1098C>ASNV Likely benign 314431 rs8017287 14:76113913-76113913 14:75647570-75647570
39 FLVCR2 NM_017791.3(FLVCR2):c.1441G>A (p.Ala481Thr)SNV Benign/Likely benign 314418 rs35126362 14:76107624-76107624 14:75641281-75641281
40 FLVCR2 NM_017791.3(FLVCR2):c.376C>T (p.Leu126=)SNV Benign/Likely benign 95817 rs8011292 14:76045691-76045691 14:75579348-75579348
41 FLVCR2 NM_017791.3(FLVCR2):c.47T>C (p.Val16Ala)SNV Benign 95818 rs2287015 14:76045362-76045362 14:75579019-75579019
42 FLVCR2 NM_017791.3(FLVCR2):c.543G>A (p.Val181=)SNV Benign 95819 rs2287016 14:76045858-76045858 14:75579515-75579515
43 FLVCR2 NM_017791.3(FLVCR2):c.648C>G (p.Ser216=)SNV Benign 95820 rs2287017 14:76045963-76045963 14:75579620-75579620
44 FLVCR2 NM_017791.2(FLVCR2):c.-356G>CSNV Benign 314403 rs3813550 14:76044960-76044960 14:75578617-75578617
45 FLVCR2 NM_017791.3(FLVCR2):c.-96T>CSNV Benign 314406 rs11845734 14:76045220-76045220 14:75578877-75578877
46 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...

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....