MCID: HYP347
MIFTS: 46

Hypotonia-Cystinuria Syndrome

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

Aliases & Classifications for Hypotonia-Cystinuria Syndrome

MalaCards integrated aliases for Hypotonia-Cystinuria Syndrome:

Name: Hypotonia-Cystinuria Syndrome 57 12 59 75 29 13 15 73
Cystinuria with Mitochondrial Disease 57 12
Hcs 59 75
Homozygous 2p16 Deletion Syndrome, Formerly 57
Atypical Hypotonia-Cystinuria Syndrome 59
2p21 Microdeletion Syndrome 59
2p21 Deletion Syndrome 59
Monosomy 2p21 59
Atypical Hcs 59
Del(2)(p21) 59

Characteristics:

Orphanet epidemiological data:

59
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
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:

32
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 eye, and related phenotypes are hypogonadism and low-set, posteriorly rotated ears

UniProtKB/Swiss-Prot : 75 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 all 17)
# Related Disease Score Top Affiliating Genes
1 2p21 microdeletion syndrome without cystinuria 33.7 CAMKMT PREPL
2 cystinuria 30.0 CAMKMT PREPL SLC3A1 SLC7A9
3 hajdu-cheney syndrome 11.6
4 hemicrania continua 11.3
5 holocarboxylase synthetase deficiency 11.3
6 hemochromatosis, type 1 10.9
7 hypotonia 10.5
8 tetanus 10.0
9 amino acid metabolic disorder 10.0 SLC3A1 SLC7A9
10 baraitser-winter cerebrofrontofacial syndrome 9.9 ACTB ACTG1
11 neuroblastoma 9.9
12 type i 9.9
13 congenital ptosis 9.9 ACTB ACTG1
14 baraitser-winter syndrome 9.8 ACTB ACTG1
15 breast cancer 9.7
16 down syndrome 9.7
17 aminoaciduria 9.7 SLC3A1 SLC7A9

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



Diseases related to Hypotonia-Cystinuria Syndrome

Symptoms & Phenotypes for Hypotonia-Cystinuria Syndrome

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Hypotonia-Cystinuria Syndrome:

59 32 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypogonadism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000135
2 low-set, posteriorly rotated ears 59 32 hallmark (90%) Very frequent (99-80%) HP:0000368
3 long eyelashes 59 32 hallmark (90%) Very frequent (99-80%) HP:0000527
4 nephrolithiasis 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000787
5 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
6 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001252
7 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
8 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001508
9 growth delay 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001510
10 decreased fetal movement 59 32 hallmark (90%) Occasional (29-5%),Very frequent (99-80%) HP:0001558
11 nasal speech 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001611
12 hypoglycemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001943
13 frontal bossing 59 32 frequent (33%) Very frequent (99-80%),Frequent (79-30%) HP:0002007
14 intellectual disability, moderate 59 32 hallmark (90%) Very frequent (99-80%) HP:0002342
15 hypocalcemia 59 32 frequent (33%) Frequent (79-30%) HP:0002901
16 lactic acidosis 59 32 frequent (33%) Frequent (79-30%) HP:0003128
17 cystinuria 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0003131
18 depressed nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0005280
19 mitochondrial respiratory chain defects 59 32 hallmark (90%) Very frequent (99-80%) HP:0200125
20 dolichocephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000268
21 retrognathia 59 32 frequent (33%) Frequent (79-30%) HP:0000278
22 epicanthus 59 32 frequent (33%) Frequent (79-30%) HP:0000286
23 ptosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000508
24 polyphagia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002591
25 fatigue 59 32 frequent (33%) Frequent (79-30%) HP:0012378
26 posteriorly rotated ears 32 HP:0000358
27 macrotia 32 HP:0000400
28 hypergonadotropic hypogonadism 32 HP:0000815
29 growth hormone deficiency 32 HP:0000824
30 generalized hypotonia 32 HP:0001290
31 neonatal hypotonia 32 HP:0001319
32 neonatal hypoglycemia 32 HP:0001998
33 feeding difficulties in infancy 32 HP:0008872
34 facial palsy 32 HP:0010628
35 tented upper lip vermilion 32 HP:0010804
36 intellectual disability, severe 32 HP:0010864
37 central hypotonia 32 HP:0011398

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 Not Applicable
4 Hormones 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 29

Anatomical Context for Hypotonia-Cystinuria Syndrome

MalaCards organs/tissues related to Hypotonia-Cystinuria Syndrome:

41
Eye

Publications for Hypotonia-Cystinuria Syndrome

Articles related to Hypotonia-Cystinuria Syndrome:

# Title Authors Year
1
First cardiac manifestation of hypotonia-cystinuria syndrome. ( 29627929 )
2018
2
Causality between myopathic hypotonia-cystinuria syndrome (HCS) and noncompaction (LVHT) is not compelling. ( 29936637 )
2018
3
Two novel deletions in hypotonia-cystinuria syndrome. ( 22796000 )
2012
4
2p21 Deletions in hypotonia-cystinuria syndrome. ( 22766003 )
2012
5
Evaluation of the pediatric patient with hypotonia: don't forget the hypotonia-cystinuria syndrome! ( 22211458 )
2012
6
Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria syndrome. ( 21686663 )
2009
7
Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria syndrome. ( 18234729 )
2008
8
Global distribution of the most prevalent deletions causing hypotonia-cystinuria syndrome. ( 17579669 )
2007
9
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 9.32 SLC3A1 SLC7A9
2 platelet aggregation GO:0070527 9.26 ACTB ACTG1
3 retina homeostasis GO:0001895 9.16 ACTB ACTG1
4 cell junction assembly GO:0034329 8.96 ACTB ACTG1
5 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 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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