HCS
MCID: HYP347
MIFTS: 50

Hypotonia-Cystinuria Syndrome (HCS)

Categories: Endocrine diseases, Fetal diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Hypotonia-Cystinuria Syndrome

MalaCards integrated aliases for Hypotonia-Cystinuria Syndrome:

Name: Hypotonia-Cystinuria Syndrome 58 12 60 76 30 15 74
Cystinuria with Mitochondrial Disease 58 12
Hcs 60 76
Homozygous 2p16 Deletion Syndrome, Formerly 58
Atypical Hypotonia-Cystinuria Syndrome 60
2p21 Microdeletion Syndrome 60
2p21 Deletion Syndrome 60
Monosomy 2p21 60
Atypical Hcs 60
Del(2)(p21) 60

Characteristics:

Orphanet epidemiological data:

60
hypotonia-cystinuria syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;
2p21 microdeletion syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;
atypical hypotonia-cystinuria syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
both contiguous gene syndromes show similar features such as cystinuria, growth impairment, and hypotonia
however, neonatal seizures, severe mental retardation, distinct dysmorphic features, and mitochondrial dysfunction are unique to 2p21 deletion syndrome (2p21del)
hypotonia may respond to treatment with pyridostigmine


HPO:

33
hypotonia-cystinuria syndrome:
Inheritance contiguous gene syndrome autosomal recessive inheritance


Classifications:



Summaries for Hypotonia-Cystinuria Syndrome

Disease Ontology : 12 A syndrome that has material basis in homozygous deletion on chromosome 2p21 that disrupts the SLC3A1 and PREPL genes. The deletion ranges in size from 23.8 to 75.5 kb. Itis characterized_by neonatal and infantile hypotonia and failure to thrive, cystinuria type 1 and nephrolithiasis, growth retardation due to growth hormone deficiency, and minor facial dysmorphism.

MalaCards based summary : Hypotonia-Cystinuria Syndrome, also known as cystinuria with mitochondrial disease, is related to 2p21 microdeletion syndrome without cystinuria and cystinuria. An important gene associated with Hypotonia-Cystinuria Syndrome is DEL2P21 (Hypotonia-Cystinuria Syndrome), and among its related pathways/superpathways are Myometrial Relaxation and Contraction Pathways and Cytoskeletal Signaling. The drugs Sulfamethoxazole and Anti-Infective Agents have been mentioned in the context of this disorder. Affiliated tissues include prostate, eye and brain, and related phenotypes are frontal bossing and ptosis

UniProtKB/Swiss-Prot : 76 Hypotonia-cystinuria syndrome: Characterized generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, failure to thrive, followed by hyperphagia and rapid weight gain in late childhood.

Description from OMIM: 606407

Related Diseases for Hypotonia-Cystinuria Syndrome

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

(show top 50) (show all 75)
# Related Disease Score Top Affiliating Genes
1 2p21 microdeletion syndrome without cystinuria 33.8 CAMKMT PREPL
2 cystinuria 30.7 CAMKMT PREPL SLC3A1 SLC7A9
3 hajdu-cheney syndrome 11.8
4 holocarboxylase synthetase deficiency 11.8
5 hemicrania continua 11.5
6 zinc, elevated plasma 11.1
7 hemochromatosis, type 1 11.1
8 hypotonia 10.7
9 tetanus 10.4
10 myasthenic syndrome, congenital, 22 10.2 CAMKMT PREPL
11 nevus comedonicus 10.1
12 cystic fibrosis 10.1
13 foodborne botulism 10.1
14 breast cancer 10.0
15 frasier syndrome 10.0
16 rheumatoid arthritis 10.0
17 heparin cofactor ii deficiency 10.0
18 blood group, junior system 10.0
19 cholangiocarcinoma 10.0
20 pemphigus foliaceus 10.0
21 hermansky-pudlak syndrome 10.0
22 intrahepatic cholangiocarcinoma 10.0
23 hemorrhoid 10.0
24 polymyositis 10.0
25 baraitser-winter cerebrofrontofacial syndrome 10.0 ACTB ACTG1
26 amino acid metabolic disorder 10.0 SLC3A1 SLC7A9
27 congenital ptosis 9.9 ACTB ACTG1
28 baraitser-winter syndrome 9.9 ACTB ACTG1
29 aminoaciduria 9.9 SLC3A1 SLC7A9
30 blood group system, landsteiner-wiener 9.8
31 neurofibromatosis, type i 9.8
32 neurofibromatosis, type iv, of riccardi 9.8
33 neutrophil migration 9.8
34 prostate cancer 9.8
35 down syndrome 9.8
36 varicose veins 9.8
37 vertigo, benign recurrent 9.8
38 disorganization, mouse, homolog of 9.8
39 polycythemia vera 9.8
40 prostate cancer, hereditary, 8 9.8
41 prostate cancer, hereditary, 6 9.8
42 deafness-infertility syndrome 9.8
43 pulmonary hypertension, primary, 3 9.8
44 blood group, gerbich system 9.8
45 autoimmune lymphoproliferative syndrome, type v 9.8
46 erythrocytosis, familial, 6 9.8
47 erythrocytosis, familial, 7 9.8
48 arthritis 9.8
49 brain injury 9.8
50 bronchopulmonary dysplasia 9.8

Graphical network of the top 20 diseases related to Hypotonia-Cystinuria Syndrome:



Diseases related to Hypotonia-Cystinuria Syndrome

Symptoms & Phenotypes for Hypotonia-Cystinuria Syndrome

Human phenotypes related to Hypotonia-Cystinuria Syndrome:

60 33 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 frontal bossing 60 33 frequent (33%) Very frequent (99-80%),Frequent (79-30%) HP:0002007
2 ptosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000508
3 muscular hypotonia 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001252
4 failure to thrive 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001508
5 global developmental delay 60 33 hallmark (90%) Very frequent (99-80%) HP:0001263
6 depressed nasal bridge 60 33 hallmark (90%) Very frequent (99-80%) HP:0005280
7 dolichocephaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0000268
8 growth delay 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001510
9 hypogonadism 60 33 hallmark (90%) Very frequent (99-80%) HP:0000135
10 intellectual disability, moderate 60 33 hallmark (90%) Very frequent (99-80%) HP:0002342
11 low-set, posteriorly rotated ears 60 33 hallmark (90%) Very frequent (99-80%) HP:0000368
12 nasal speech 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001611
13 nephrolithiasis 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000787
14 mitochondrial respiratory chain defects 60 33 hallmark (90%) Very frequent (99-80%) HP:0200125
15 long eyelashes 60 33 hallmark (90%) Very frequent (99-80%) HP:0000527
16 decreased fetal movement 60 33 hallmark (90%) Occasional (29-5%),Very frequent (99-80%) HP:0001558
17 cystinuria 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0003131
18 polyphagia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002591
19 seizures 60 33 frequent (33%) Frequent (79-30%) HP:0001250
20 fatigue 60 33 frequent (33%) Frequent (79-30%) HP:0012378
21 retrognathia 60 33 frequent (33%) Frequent (79-30%) HP:0000278
22 epicanthus 60 33 frequent (33%) Frequent (79-30%) HP:0000286
23 lactic acidosis 60 33 frequent (33%) Frequent (79-30%) HP:0003128
24 hypocalcemia 60 33 frequent (33%) Frequent (79-30%) HP:0002901
25 hypoglycemia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001943
26 facial palsy 33 HP:0010628
27 macrotia 33 HP:0000400
28 neonatal hypotonia 33 HP:0001319
29 feeding difficulties in infancy 33 HP:0008872
30 intellectual disability, severe 33 HP:0010864
31 hypergonadotropic hypogonadism 33 HP:0000815
32 tented upper lip vermilion 33 HP:0010804
33 neonatal hypoglycemia 33 HP:0001998
34 generalized hypotonia 33 HP:0001290
35 posteriorly rotated ears 33 HP:0000358
36 growth hormone deficiency 33 HP:0000824
37 central hypotonia 33 HP:0011398

Symptoms via clinical synopsis from OMIM:

58
Growth Weight:
rapid weight gain in late childhood (hcs)

Head And Neck Head:
dolichocephaly (hcs)

Head And Neck Ears:
large ears (2p21del)
posteriorly rotated ears (2p21del)

Skin Nails Hair Hair:
long eyelashes (2p21del)

Head And Neck Mouth:
tented upper lip (hcs)

Genitourinary Kidneys:
nephrolithiasis (hcs and 2p21del)

Muscle Soft Tissue:
hypotonia, neonatal, severe (hcs)
muscle weakness (hcs)
myasthenic syndrome (hcs)
red-ragged fibers (2p21del)
normal muscle fiber (hcs)

Neurologic Behavioral Psychiatric Manifestations:
hyperphagia in late childhood (hcs)

Metabolic Features:
cystinuria, type i (hcs and 2p21del)

Prenatal Manifestations Movement:
decreased fetal movements (2p21del and hcs)

Laboratory Abnormalities:
lactic acidemia (2p21del)
normal lactate (hcs)
transient neonatal hypocalcemia (2p21del)
transient neonatal hypoglycemia (2p21del)
increased urinary cystine, arginine, lysine, and ornithine (hcs and 2p21del)
more
Growth Other:
failure to thrive (birth to 6-8 years) (hcs)
failure to thrive, severe (2p21del)

Head And Neck Face:
frontal bossing (2p21del)
facial weakness (hcs)

Head And Neck Eyes:
almond-shaped eyes (2p21del)
long eyelashes (2p21del)
ptosis (hcs)

Head And Neck Nose:
depressed nasal bridge (2p21del)

Abdomen Gastrointestinal:
feeding problems (hcs and 2p21del)

Genitourinary Bladder:
bladder cystine calculi (2p21del)

Neurologic Central Nervous System:
seizures, neonatal (2p21del)
no seizures (hcs)
hypotonia (hcs and 2p21del)
developmental delay, severe (2p21del)
mental retardation, moderate-severe (2p21del)

Voice:
nasal speech (hcs)

Endocrine Features:
growth hormone deficiency (hcs)
hypergonadotropic hypogonadism (hcs)

Prenatal Manifestations Delivery:
postdates delivery (hcs)

Clinical features from OMIM:

606407

MGI Mouse Phenotypes related to Hypotonia-Cystinuria Syndrome:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.02 ACTB ACTG1 CAMKMT PREPL SLC3A1

Drugs & Therapeutics for Hypotonia-Cystinuria Syndrome

Drugs for Hypotonia-Cystinuria Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Sulfamethoxazole Approved Phase 2 723-46-6 5329
2 Anti-Infective Agents Phase 2
3 Hormones Not Applicable
4 Anesthetics Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Sulfamethoxazole for the Treatment of Primary PREPL Deficiency Unknown status NCT02640443 Phase 2 Sulfamethoxazole
2 PREPL in Health and Disease Unknown status NCT02263781 Not Applicable

Search NIH Clinical Center for Hypotonia-Cystinuria Syndrome

Genetic Tests for Hypotonia-Cystinuria Syndrome

Genetic tests related to Hypotonia-Cystinuria Syndrome:

# Genetic test Affiliating Genes
1 Hypotonia-Cystinuria Syndrome 30

Anatomical Context for Hypotonia-Cystinuria Syndrome

MalaCards organs/tissues related to Hypotonia-Cystinuria Syndrome:

42
Prostate, Eye, Brain, Heart, Breast, Neutrophil

Publications for Hypotonia-Cystinuria Syndrome

Articles related to Hypotonia-Cystinuria Syndrome:

# Title Authors Year
1
A Case of Hypotonia-Cystinuria Syndrome With Genito-Urinary Malformations and Extrarenal Involvement. ( 31024870 )
2019
2
First cardiac manifestation of hypotonia-cystinuria syndrome. ( 29627929 )
2018
3
Causality between myopathic hypotonia-cystinuria syndrome (HCS) and noncompaction (LVHT) is not compelling. ( 29936637 )
2018
4
Evaluation of the pediatric patient with hypotonia: don't forget the hypotonia-cystinuria syndrome! ( 22211458 )
2012
5
2p21 Deletions in hypotonia-cystinuria syndrome. ( 22766003 )
2012
6
Two novel deletions in hypotonia-cystinuria syndrome. ( 22796000 )
2012
7
Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria syndrome. ( 21686663 )
2009
8
Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria syndrome. ( 18234729 )
2008
9
Global distribution of the most prevalent deletions causing hypotonia-cystinuria syndrome. ( 17579669 )
2007
10
Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. ( 16385448 )
2006

Variations for Hypotonia-Cystinuria Syndrome

Copy number variations for Hypotonia-Cystinuria Syndrome from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 145632 2 41600000 47600000 Deletion PREPL Hypotonia-Cystinuria syndrome
2 145634 2 41600000 47600000 Deletion SLC3A1 Hypotonia-Cystinuria syndrome

Expression for Hypotonia-Cystinuria Syndrome

Search GEO for disease gene expression data for Hypotonia-Cystinuria Syndrome.

Pathways for Hypotonia-Cystinuria Syndrome

GO Terms for Hypotonia-Cystinuria Syndrome

Cellular components related to Hypotonia-Cystinuria Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.92 ACTB ACTG1 CALD1 CAMKMT PPM1B PREP
2 cytoskeleton GO:0005856 9.55 ACTB ACTG1 CALD1 PREPL ZYX
3 brush border membrane GO:0031526 9.37 SLC3A1 SLC7A9
4 myofibril GO:0030016 9.26 ACTG1 CALD1
5 actin cytoskeleton GO:0015629 9.13 ACTB ACTG1 CALD1
6 dense body GO:0097433 8.62 ACTB ACTG1

Biological processes related to Hypotonia-Cystinuria Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 amino acid transport GO:0006865 9.37 SLC3A1 SLC7A9
2 platelet aggregation GO:0070527 9.32 ACTB ACTG1
3 retina homeostasis GO:0001895 9.26 ACTB ACTG1
4 cell junction assembly GO:0034329 9.16 ACTB ACTG1
5 L-alpha-amino acid transmembrane transport GO:1902475 8.65 SLC7A9
6 L-cystine transport GO:0015811 8.62 SLC3A1 SLC7A9

Molecular functions related to Hypotonia-Cystinuria Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 amino acid transmembrane transporter activity GO:0015171 9.16 SLC3A1 SLC7A9
2 L-cystine transmembrane transporter activity GO:0015184 8.96 SLC3A1 SLC7A9
3 serine-type exopeptidase activity GO:0070008 8.62 PREP PREPL

Sources for Hypotonia-Cystinuria Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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