HCS
MCID: HYP347
MIFTS: 41

Hypotonia-Cystinuria Syndrome (HCS)

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

Aliases & Classifications for Hypotonia-Cystinuria Syndrome

MalaCards integrated aliases for Hypotonia-Cystinuria Syndrome:

Name: Hypotonia-Cystinuria Syndrome 57 12 58 73 29 13 15 71
Cystinuria with Mitochondrial Disease 57 12
Hcs 58 73
Homozygous 2p16 Deletion Syndrome, Formerly 57
Atypical Hypotonia-Cystinuria Syndrome 58
2p21 Microdeletion Syndrome 58
2p21 Deletion Syndrome 58
Monosomy 2p21 58
Atypical Hcs 58
Del(2)(p21) 58

Characteristics:

Orphanet epidemiological data:

58
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®:

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

Miscellaneous:
both contiguous gene syndromes show similar features such as cystinuria, growth impairment, and hypotonia
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:

31
hypotonia-cystinuria syndrome:
Inheritance autosomal recessive inheritance contiguous gene syndrome


Classifications:

Orphanet: 58  
Rare renal diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis


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 is Amino acid transport across the plasma membrane. The drugs Sulfamethoxazole and Anti-Infective Agents have been mentioned in the context of this disorder. Related phenotypes are failure to thrive and frontal bossing

UniProtKB/Swiss-Prot : 73 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.

More information from OMIM: 606407

Related Diseases for Hypotonia-Cystinuria Syndrome

Diseases in the Hypotonia-Cystinuria Syndrome family:

Hypotonia-Cystinuria Type 1 Syndrome

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

(show all 46)
# Related Disease Score Top Affiliating Genes
1 2p21 microdeletion syndrome without cystinuria 32.3 PREPL CAMKMT
2 cystinuria 30.6 SLC7A9 SLC7A13 SLC3A1 SLC1A7 PREPL PREP
3 hajdu-cheney syndrome 11.3
4 holocarboxylase synthetase deficiency 11.3
5 homozygous 2p21 microdeletion syndrome 11.2
6 hypotonia 10.5
7 chondrosarcoma 10.4
8 myasthenic syndrome, congenital, 22 10.2 SLC3A1 PREPL PREP CAMKMT
9 urolithiasis 10.2 SLC7A9 SLC3A1 PREPL
10 nephrolithiasis 10.2
11 growth hormone deficiency 10.2
12 ureteral disease 10.2 SLC7A9 SLC3A1 SLC1A7 PREPL
13 aminoaciduria 10.2 SLC7A9 SLC3A1
14 amino acid metabolic disorder 10.1 SLC7A9 SLC3A1 SLC1A7
15 agnathia-otocephaly complex 10.1 TEX30 AADACL4 AADACL2
16 multiple carboxylase deficiency 10.1
17 47,xyy 10.1
18 hartnup disorder 10.0 SLC3A1 SLC1A7
19 nephrolithiasis, calcium oxalate 10.0
20 cryptorchidism, unilateral or bilateral 10.0
21 autosomal recessive disease 10.0
22 cakut 10.0
23 dilated cardiomyopathy 10.0
24 patent foramen ovale 10.0
25 osteogenic sarcoma 10.0
26 cervical cancer 10.0
27 pre-eclampsia 10.0
28 arthropathy 10.0
29 osteoarthritis 10.0
30 colorectal cancer 9.8
31 prostate cancer 9.8
32 down syndrome 9.8
33 varicose veins 9.8
34 branchiootic syndrome 1 9.8
35 intraocular pressure quantitative trait locus 9.8
36 pachyonychia congenita 3 9.8
37 bone sarcoma 9.8
38 gestational diabetes 9.8
39 dementia 9.8
40 eclampsia 9.8
41 rh isoimmunization 9.8
42 keratinizing squamous cell carcinoma 9.8
43 auditory neuropathy spectrum disorder 9.8
44 dwarfism 9.8
45 osteochondroma 9.8
46 brain injury 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:

58 31 (show all 38)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001508
2 frontal bossing 58 31 frequent (33%) Frequent (79-30%),Very frequent (99-80%) HP:0002007
3 ptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000508
4 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
5 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
6 growth delay 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001510
7 dolichocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000268
8 low-set, posteriorly rotated ears 58 31 hallmark (90%) Very frequent (99-80%) HP:0000368
9 nephrolithiasis 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000787
10 intellectual disability, moderate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002342
11 nasal speech 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001611
12 decreased fetal movement 58 31 hallmark (90%) Very frequent (99-80%),Occasional (29-5%) HP:0001558
13 long eyelashes 58 31 hallmark (90%) Very frequent (99-80%) HP:0000527
14 hypogonadism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000135
15 polyphagia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002591
16 cystinuria 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0003131
17 mitochondrial respiratory chain defects 58 31 hallmark (90%) Very frequent (99-80%) HP:0200125
18 hypotonia 31 hallmark (90%) HP:0001252
19 fatigue 58 31 frequent (33%) Frequent (79-30%) HP:0012378
20 retrognathia 58 31 frequent (33%) Frequent (79-30%) HP:0000278
21 epicanthus 58 31 frequent (33%) Frequent (79-30%) HP:0000286
22 hypocalcemia 58 31 frequent (33%) Frequent (79-30%) HP:0002901
23 lactic acidosis 58 31 frequent (33%) Frequent (79-30%) HP:0003128
24 seizure 31 frequent (33%) HP:0001250
25 hypoglycemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001943
26 seizures 58 Frequent (79-30%)
27 facial palsy 31 HP:0010628
28 muscular hypotonia 58 Very frequent (99-80%),Very frequent (99-80%)
29 macrotia 31 HP:0000400
30 neonatal hypotonia 31 HP:0001319
31 feeding difficulties in infancy 31 HP:0008872
32 intellectual disability, severe 31 HP:0010864
33 tented upper lip vermilion 31 HP:0010804
34 neonatal hypoglycemia 31 HP:0001998
35 hypergonadotropic hypogonadism 31 HP:0000815
36 posteriorly rotated ears 31 HP:0000358
37 generalized hypotonia 31 HP:0001290
38 decreased response to growth hormone stimuation test 31 HP:0000824

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
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 (Updated 05-Mar-2021)

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 Anesthetics
4 Hormones

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (In Dutch: Sulfamethoxazole Ter Behandeling Van Primaire PREPL deficiëntie) Unknown status NCT02640443 Phase 2 Sulfamethoxazole
2 PREPL in Health and Disease Unknown status NCT02263781

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 29

Anatomical Context for Hypotonia-Cystinuria Syndrome

Publications for Hypotonia-Cystinuria Syndrome

Articles related to Hypotonia-Cystinuria Syndrome:

(show all 21)
# Title Authors PMID Year
1
PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. 57 61
24610330 2014
2
Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria syndrome. 61 57
18234729 2008
3
Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. 61 57
16385448 2006
4
The 2p21 deletion syndrome: characterization of the transcription content. 57
15913950 2005
5
A recessive contiguous gene deletion of chromosome 2p16 associated with cystinuria and a mitochondrial disease. 57
11524703 2001
6
A Case of Hypotonia-Cystinuria Syndrome With Genito-Urinary Malformations and Extrarenal Involvement. 61
31024870 2019
7
Causality between myopathic hypotonia-cystinuria syndrome (HCS) and noncompaction (LVHT) is not compelling. 61
29936637 2018
8
First cardiac manifestation of hypotonia-cystinuria syndrome. 61
29627929 2018
9
PREPL deficiency: delineation of the phenotype and development of a functional blood assay. 61
28726805 2018
10
Deletion of PREPl causes growth impairment and hypotonia in mice. 61
24586561 2014
11
Further delineation of genotype-phenotype correlation in homozygous 2p21 deletion syndromes: first description of patients without cystinuria. 61
23794250 2013
12
Cellular and ultra structural evidence for cytoskeletal localization of prolyl endopeptidase-like protein in neurons. 61
23485813 2013
13
Two novel deletions in hypotonia-cystinuria syndrome. 61
22796000 2012
14
2p21 Deletions in hypotonia-cystinuria syndrome. 61
22766003 2012
15
Cystinuria: an inborn cause of urolithiasis. 61
22480232 2012
16
Evaluation of the pediatric patient with hypotonia: don't forget the hypotonia-cystinuria syndrome! 61
22211458 2012
17
A substrate-free activity-based protein profiling screen for the discovery of selective PREPL inhibitors. 61
21692504 2011
18
Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria syndrome. 61
21686663 2009
19
Multi-system disorder syndromes associated with cystinuria type I. 61
18781961 2008
20
Global distribution of the most prevalent deletions causing hypotonia-cystinuria syndrome. 61
17579669 2007
21
PREPL: a putative novel oligopeptidase propelled into the limelight. 61
16913837 2006

Variations for Hypotonia-Cystinuria Syndrome

Copy number variations for Hypotonia-Cystinuria Syndrome from CNVD:

7
# CNVD ID Chromosome 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

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.14 SLC7A9 SLC3A1

GO Terms for Hypotonia-Cystinuria Syndrome

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 9.33 SLC7A9 SLC7A13 SLC3A1
2 L-alpha-amino acid transmembrane transport GO:1902475 9.26 SLC7A9 SLC7A13
3 L-cystine transport GO:0015811 8.96 SLC7A9 SLC3A1
4 amino acid transmembrane transport GO:0003333 8.8 SLC7A9 SLC7A13 SLC3A1

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

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.76 TEX30 RBBP9 PREPL PREP PPM1B LYPLA2
2 amino acid transmembrane transporter activity GO:0015171 9.32 SLC7A9 SLC3A1
3 L-amino acid transmembrane transporter activity GO:0015179 9.26 SLC7A9 SLC7A13
4 carboxylic ester hydrolase activity GO:0052689 9.13 LYPLA2 AADACL4 AADACL2
5 L-cystine transmembrane transporter activity GO:0015184 8.62 SLC7A9 SLC3A1

Sources for Hypotonia-Cystinuria 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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