NLS1
MCID: NLX004
MIFTS: 49

Neu-Laxova Syndrome 1 (NLS1)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Neu-Laxova Syndrome 1

MalaCards integrated aliases for Neu-Laxova Syndrome 1:

Name: Neu-Laxova Syndrome 1 58 12 76 30 6
Neu-Laxova Syndrome 58 60 38 30 41 74
Neu Laxova Syndrome 77 54
Nls1 58 76
Nls 58 54
3-Phosphoglycerate Dehydrogenase Deficiency, Neonatal Form 60
Neu-Laxova Syndrome; Nls 58

Characteristics:

Orphanet epidemiological data:

60
neu-laxova syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal; Age of death: infantile,stillbirth;

OMIM:

58
Miscellaneous:
polyhydramnios
short umbilical cord
small placenta
stillborn
decreased fetal activity
most patients are stillborn or die in immediate neonatal period

Inheritance:
autosomal recessive


HPO:

33
neu-laxova syndrome 1:
Clinical modifier stillbirth
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Neu-Laxova Syndrome 1

NIH Rare Diseases : 54 Neu Laxova syndrome (NLS) is a genetic disorder affecting many parts of the body. Babies born with NLS usually grow poorly during pregnancy (intrauterine growth restriction). At birth, they may be small (low birth weight and short in length) and their facial features are usually different and distinct. The babies may have a small head (microcephaly), sloping forehead, and widely spaced eyes (hypertelorism). Babies with NLS may also have extra fluid (edema) in their hands and feet, brain abnormalities, and rigid, stiff muscles. Other birth defects may affect the baby's arms, legs, skin, genitals, kidneys, and heart. Not every baby with NLS will have every sign or symptom of NLS. Neu Laxova syndrome (NLS) is caused by changes or mutations in one of three different genes, PHGDH, PSAT1, PSPH. The mutations cause too little L-serine (an amino acid) to be made. There must be a mutation in both copies of one of these genes, which means NLS is inherited in an autosomal recessive manner. NLS can be diagnosed both prenatally by an ultrasound or after birth. The diagnosis is suspected by signs and symptoms, but may be confirmed by genetic testing (prenatally by chorionic villi sampling (CVS) or amniocentesis; after birth by genetic blood test). There is no cure or treatment for NLS at this time, but L-serine supplementation may prove to be an effective treatment in the future if the NLS is found early during a pregnancy. 

MalaCards based summary : Neu-Laxova Syndrome 1, also known as neu-laxova syndrome, is related to microcephaly and phosphoglycerate dehydrogenase deficiency. An important gene associated with Neu-Laxova Syndrome 1 is PHGDH (Phosphoglycerate Dehydrogenase), and among its related pathways/superpathways are Glycine, serine and threonine metabolism and Vitamin B6 metabolism. The drugs Mazindol and Dopamine have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and brain, and related phenotypes are thick vermilion border and microcephaly

Disease Ontology : 12 A serine deficiency that is characterized by multiple fatal malformations including ichthyosis, microcephaly, central nervous system abnormalities, limb deformities, intrauterine growth restriction, proptosis, anasarca, and micrognathia, and has material basis in autosomal recessive inheritance of mutation in the PHGDH gene on chromosome 1p12, causing issues producing the amino acid serine.

OMIM : 58 Neu-Laxova syndrome is an autosomal recessive lethal multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, central nervous system anomalies (lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum), limb deformities, hypoplastic lungs, edema, and abnormal facial features including severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears (summary by Manning et al., 2004). (256520)

UniProtKB/Swiss-Prot : 76 Neu-Laxova syndrome 1: A lethal, autosomal recessive multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, limb deformities, hypoplastic lungs, edema, and central nervous system anomalies including lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum. Abnormal facial features include severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears.

Wikipedia : 77 Neu–Laxova syndrome (also known as Neu syndrome or Neu-Povysilová syndrome, abbreviated as NLS) is a... more...

Related Diseases for Neu-Laxova Syndrome 1

Graphical network of the top 20 diseases related to Neu-Laxova Syndrome 1:



Diseases related to Neu-Laxova Syndrome 1

Symptoms & Phenotypes for Neu-Laxova Syndrome 1

Human phenotypes related to Neu-Laxova Syndrome 1:

60 33 (show top 50) (show all 95)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 thick vermilion border 60 33 hallmark (90%) Very frequent (99-80%) HP:0012471
2 microcephaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0000252
3 ichthyosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0008064
4 lack of skin elasticity 60 33 hallmark (90%) Very frequent (99-80%) HP:0100679
5 intrauterine growth retardation 60 33 hallmark (90%) Very frequent (99-80%) HP:0001511
6 sloping forehead 60 33 hallmark (90%) Very frequent (99-80%) HP:0000340
7 hypertelorism 60 33 frequent (33%) Frequent (79-30%) HP:0000316
8 macrotia 60 33 frequent (33%) Frequent (79-30%) HP:0000400
9 skeletal muscle atrophy 60 33 frequent (33%) Frequent (79-30%) HP:0003202
10 everted lower lip vermilion 60 33 frequent (33%) Frequent (79-30%) HP:0000232
11 hypogonadism 60 33 frequent (33%) Frequent (79-30%) HP:0000135
12 cerebellar hypoplasia 60 33 frequent (33%) Frequent (79-30%) HP:0001321
13 depressed nasal ridge 60 33 frequent (33%) Frequent (79-30%) HP:0000457
14 polyhydramnios 60 33 frequent (33%) Frequent (79-30%) HP:0001561
15 proptosis 60 33 frequent (33%) Frequent (79-30%) HP:0000520
16 absent septum pellucidum 60 33 frequent (33%) Frequent (79-30%) HP:0001331
17 decreased fetal movement 60 33 frequent (33%) Frequent (79-30%) HP:0001558
18 ambiguous genitalia 60 33 frequent (33%) Frequent (79-30%) HP:0000062
19 trismus 60 33 frequent (33%) Frequent (79-30%) HP:0000211
20 pachygyria 60 33 frequent (33%) Frequent (79-30%) HP:0001302
21 polymicrogyria 60 33 frequent (33%) Frequent (79-30%) HP:0002126
22 large hands 60 33 frequent (33%) Frequent (79-30%) HP:0001176
23 dandy-walker malformation 60 33 frequent (33%) Frequent (79-30%) HP:0001305
24 muscular dystrophy 60 33 frequent (33%) Frequent (79-30%) HP:0003560
25 broad foot 60 33 frequent (33%) Frequent (79-30%) HP:0001769
26 abnormality of the philtrum 60 33 frequent (33%) Frequent (79-30%) HP:0000288
27 opisthotonus 60 33 frequent (33%) Frequent (79-30%) HP:0002179
28 aplasia/hypoplasia involving the skeletal musculature 60 33 frequent (33%) Frequent (79-30%) HP:0001460
29 external genital hypoplasia 60 33 frequent (33%) Frequent (79-30%) HP:0003241
30 macrogyria 60 33 frequent (33%) Frequent (79-30%) HP:0007227
31 muscle spasm 33 frequent (33%) HP:0003394
32 osteopenia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000938
33 cerebral calcification 60 33 occasional (7.5%) Occasional (29-5%) HP:0002514
34 scoliosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002650
35 cataract 60 33 occasional (7.5%) Occasional (29-5%) HP:0000518
36 rickets 60 33 occasional (7.5%) Occasional (29-5%) HP:0002748
37 osteoporosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000939
38 micrognathia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000347
39 retrognathia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000278
40 micromelia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002983
41 prominent occiput 60 33 occasional (7.5%) Occasional (29-5%) HP:0000269
42 arthrogryposis multiplex congenita 60 33 occasional (7.5%) Occasional (29-5%) HP:0002804
43 spina bifida 60 33 occasional (7.5%) Occasional (29-5%) HP:0002414
44 osteomalacia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002749
45 bifid uvula 60 33 occasional (7.5%) Occasional (29-5%) HP:0000193
46 pulmonary hypoplasia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002089
47 pterygium 60 33 occasional (7.5%) Occasional (29-5%) HP:0001059
48 abnormality of cardiovascular system morphology 60 33 occasional (7.5%) Occasional (29-5%) HP:0030680
49 submucous cleft hard palate 60 33 occasional (7.5%) Occasional (29-5%) HP:0000176
50 abnormal nasolacrimal system morphology 33 occasional (7.5%) HP:0000614

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
hypertelorism
cataract
microphthalmia
absent eyelashes
protruding eyes
more
Skeletal Hands:
finger syndactyly
clinodactyly
camptodactyly
puffiness of hands

Head And Neck Mouth:
cleft palate
cleft lip
thick lips
round, gaping mouth

Cardiovascular Vascular:
patent ductus arteriosus
transposition of great vessels

Cardiovascular Heart:
atrial septal defect
ventricular septal defect
patent foramen ovale

Skeletal Feet:
toe syndactyly
vertical talus
calcaneovalgus
puffiness of feet

Skin Nails Hair Hair:
absent eyelashes
absent scalp hair

Genitourinary Internal Genitalia Female:
bifid uterus

Skeletal Limbs:
short limbs
pterygia
flexion contractures of joints

Growth Other:
prenatal onset growth retardation

Skin Nails Hair Skin:
yellow subcutaneous tissue covered by thin, scaly skin
generalized tissue edema

Head And Neck Neck:
short neck

Head And Neck Head:
microcephaly

Head And Neck Face:
micrognathia
sloping forehead

Genitourinary Internal Genitalia Male:
cryptorchidism

Neurologic Central Nervous System:
cerebellar hypoplasia
spina bifida
dandy-walker malformation
hydranencephaly
lissencephaly
more
Respiratory Lung:
pulmonary hypoplasia

Genitourinary Kidneys:
renal agenesis

Head And Neck Ears:
large ears

Head And Neck Nose:
flattened nose

Skeletal:
poorly mineralized bones

Clinical features from OMIM:

256520

Drugs & Therapeutics for Neu-Laxova Syndrome 1

Drugs for Neu-Laxova Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Mazindol Approved, Investigational Phase 2 22232-71-9 4020
2
Dopamine Approved Phase 2 62-31-7, 51-61-6 681
3 Central Nervous System Stimulants Phase 2
4 Dopamine Uptake Inhibitors Phase 2
5 Adrenergic Agents Phase 2
6 Neurotransmitter Agents Phase 2
7 Dopamine Agents Phase 2
8 Neurotransmitter Uptake Inhibitors Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Mazindol Controlled Release in Adults With Attention Deficit Hyperactivity Disorder (ADHD) Completed NCT02808104 Phase 2 mazindol

Search NIH Clinical Center for Neu-Laxova Syndrome 1

Genetic Tests for Neu-Laxova Syndrome 1

Genetic tests related to Neu-Laxova Syndrome 1:

# Genetic test Affiliating Genes
1 Neu-Laxova Syndrome 30
2 Neu-Laxova Syndrome 1 30 PHGDH

Anatomical Context for Neu-Laxova Syndrome 1

MalaCards organs/tissues related to Neu-Laxova Syndrome 1:

42
Skin, Eye, Brain, Kidney, Testes, Skeletal Muscle, Uterus

Publications for Neu-Laxova Syndrome 1

Articles related to Neu-Laxova Syndrome 1:

(show top 50) (show all 62)
# Title Authors Year
1
Neu Laxova syndrome. ( 30706883 )
2019
2
Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis. ( 30838783 )
2019
3
Neu-Laxova Syndrome: An Unusual Association with Kyphosis. ( 28272663 )
2018
4
Prenatal genetic diagnosis of Neu-Laxova syndrome. ( 28903583 )
2018
5
A New Case of Neu-Laxova Syndrome: Infant with Facial Dysmorphism, Arthrogryposis, Ichthyosis, and Microcephalia. ( 29862217 )
2018
6
Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency. ( 30348640 )
2018
7
[Neu-Laxova syndrome: Three case reports and a review of the literature]. ( 27475004 )
2016
8
Identification of a premature stop codon mutation in the PHGDH gene in severe Neu-Laxova syndrome-evidence for phenotypic variability. ( 25913727 )
2015
9
Neu-Laxova syndrome: a case report. ( 24584393 )
2014
10
Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH. ( 24836451 )
2014
11
Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. ( 25152457 )
2014
12
A collodion baby with facial dysmorphism, limb anomalies, pachygyria and genital hypoplasia: a mild form of Neu-laxova syndrome or a new entity? ( 24371398 )
2013
13
Rare manifestations of Neu-Laxova syndrome. ( 22233503 )
2012
14
Neu-Laxova syndrome: a prenatal diagnosis. ( 22268252 )
2011
15
Prenatal diagnosis and postmortem findings of Neu-laxova syndrome. ( 24591943 )
2010
16
Neu-Laxova syndrome: A new patient with detailed antenatal and post-natal findings. ( 21108408 )
2010
17
A spectrum of phenotypical expression OF Neu-Laxova syndrome: Three case reports and a review of the literature. ( 20334486 )
2010
18
Neu-Laxova syndrome in an appropriate for gestational age newborn. ( 19052411 )
2008
19
Neu-Laxova syndrome, grossly appearing normal on 20 weeks ultrasonographic scan, that manifested late in pregnancy: a case report. ( 17406877 )
2007
20
Neu-Laxova syndrome: a case report and review of the literature. ( 16987270 )
2006
21
A rare cause of polyhydramnios: Neu-Laxova syndrome. ( 16923700 )
2006
22
Evaluation of a fetus with Neu-Laxova syndrome through prenatal, clinical, and pathological findings. ( 15824491 )
2005
23
Lethal arthrogryposis with icthyosis: overlap with Neu-Laxova syndrome, restrictive dermopathy and harlequin fetus. ( 15057131 )
2004
24
Neu-Laxova syndrome: detailed prenatal diagnostic and post-mortem findings and literature review. ( 14994231 )
2004
25
What syndrome is this? Neu-Laxova syndrome. ( 12558853 )
2003
26
Neu-Laxova syndrome: a case report. ( 12558841 )
2003
27
Second trimester diagnosis of Neu Laxova syndrome. ( 12533807 )
2003
28
Cerebro-osseous-digital syndrome: four new cases of a lethal skeletal dysplasia--distinct from Neu-Laxova Syndrome. ( 11977163 )
2002
29
Prenatal diagnosis of Neu-Laxova syndrome: a case report. ( 11895570 )
2002
30
Early second trimester prenatal diagnosis of Neu-Laxova syndrome. ( 11857616 )
2002
31
Prenatal sonographic diagnosis of Neu-Laxova syndrome. ( 11745866 )
2001
32
Early ultrasound diagnosis of Neu-Laxova syndrome. ( 11494295 )
2001
33
Neu-Laxova syndrome. ( 10713860 )
1999
34
A Japanese case of Neu-Laxova syndrome. ( 9575678 )
1998
35
Extreme microcephaly, severe growth and mental retardation, flexion contractures, and ichthyotic skin in two brothers: a new syndrome or mild form of Neu-Laxova syndrome? ( 9354840 )
1997
36
Qualitative analysis of fetal movement patterns in the Neu-Laxova syndrome. ( 8843479 )
1996
37
New manifestations in an infant with Neu Laxova syndrome. ( 7625453 )
1995
38
Neu-Laxova syndrome: pathological evaluation of a fetus and review of the literature. ( 8736598 )
1995
39
Sonographic diagnosis of Neu-Laxova syndrome. ( 8294578 )
1994
40
Neu-Laxova syndrome: report of a case from Turkey. ( 8375108 )
1993
41
Fetal ultrasonographic detection of hypodontia in the Neu-Laxova syndrome. ( 8227398 )
1993
42
Disorder of cerebellar foliation in Walker's lissencephaly and neu-laxova syndrome. ( 8229082 )
1993
43
Echographic, radiological and anatomo-pathological evaluation of a foetus with Neu-Laxova syndrome. ( 1632748 )
1992
44
Neu-Laxova syndrome: prenatal ultrasonographic diagnosis, clinical and pathological studies, and new manifestations. ( 1605256 )
1992
45
Neu Laxova syndrome in two Egyptian families. ( 1951459 )
1991
46
New manifestations of Neu-Laxova syndrome. ( 2405670 )
1990
47
Neu-Laxova syndrome: pathological, radiological, and prenatal findings in a stillborn female. ( 2650548 )
1989
48
Cerebral abnormalities in the Neu-Laxova syndrome. ( 3055985 )
1988
49
Neu-Laxova syndrome: a case report. ( 3348318 )
1988
50
A case of the Neu-Laxova syndrome: prenatal ultrasonographic monitoring in the third trimester and the histopathological findings. ( 3544847 )
1987

Variations for Neu-Laxova Syndrome 1

UniProtKB/Swiss-Prot genetic disease variations for Neu-Laxova Syndrome 1:

76
# Symbol AA change Variation ID SNP ID
1 PHGDH p.Gly140Arg VAR_071819 rs587777770
2 PHGDH p.Arg163Gln VAR_071820 rs587777483

ClinVar genetic disease variations for Neu-Laxova Syndrome 1:

6 (show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 PHGDH NM_006623.3(PHGDH): c.706C> T (p.Arg236Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 120277980: 120277980
2 PHGDH NM_006623.3(PHGDH): c.706C> T (p.Arg236Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 119735357: 119735357
3 PHGDH NM_006623.3(PHGDH): c.1030C> T (p.Arg344Ter) single nucleotide variant Pathogenic rs769256568 GRCh37 Chromosome 1, 120283093: 120283093
4 PHGDH NM_006623.3(PHGDH): c.1030C> T (p.Arg344Ter) single nucleotide variant Pathogenic rs769256568 GRCh38 Chromosome 1, 119740470: 119740470
5 PHGDH NM_006623.3(PHGDH): c.856G> C (p.Ala286Pro) single nucleotide variant Pathogenic rs587777775 GRCh38 Chromosome 1, 119737177: 119737177
6 PHGDH NM_006623.3(PHGDH): c.856G> C (p.Ala286Pro) single nucleotide variant Pathogenic rs587777775 GRCh37 Chromosome 1, 120279800: 120279800
7 PHGDH NM_006623.3(PHGDH): c.793G> A (p.Glu265Lys) single nucleotide variant Pathogenic rs587777774 GRCh38 Chromosome 1, 119737114: 119737114
8 PHGDH NM_006623.3(PHGDH): c.793G> A (p.Glu265Lys) single nucleotide variant Pathogenic rs587777774 GRCh37 Chromosome 1, 120279737: 120279737
9 PHGDH NM_006623.3(PHGDH): c.488G> A (p.Arg163Gln) single nucleotide variant Uncertain significance rs587777483 GRCh38 Chromosome 1, 119727080: 119727080
10 PHGDH NM_006623.3(PHGDH): c.488G> A (p.Arg163Gln) single nucleotide variant Uncertain significance rs587777483 GRCh37 Chromosome 1, 120269703: 120269703
11 PHGDH NM_006623.3(PHGDH): c.418G> A (p.Gly140Arg) single nucleotide variant Pathogenic/Likely pathogenic rs587777770 GRCh37 Chromosome 1, 120269633: 120269633
12 PHGDH NM_006623.3(PHGDH): c.418G> A (p.Gly140Arg) single nucleotide variant Pathogenic/Likely pathogenic rs587777770 GRCh38 Chromosome 1, 119727010: 119727010
13 PHGDH NM_006623.3(PHGDH): c.781G> A (p.Val261Met) single nucleotide variant Likely pathogenic rs267606947 GRCh38 Chromosome 1, 119735432: 119735432
14 PHGDH NM_006623.3(PHGDH): c.781G> A (p.Val261Met) single nucleotide variant Likely pathogenic rs267606947 GRCh37 Chromosome 1, 120278055: 120278055
15 PHGDH NM_006623.3(PHGDH): c.403C> T (p.Arg135Trp) single nucleotide variant Uncertain significance rs267606949 GRCh38 Chromosome 1, 119726897: 119726897
16 PHGDH NM_006623.3(PHGDH): c.403C> T (p.Arg135Trp) single nucleotide variant Uncertain significance rs267606949 GRCh37 Chromosome 1, 120269520: 120269520

Expression for Neu-Laxova Syndrome 1

Search GEO for disease gene expression data for Neu-Laxova Syndrome 1.

Pathways for Neu-Laxova Syndrome 1

Pathways related to Neu-Laxova Syndrome 1 according to KEGG:

38
# Name Kegg Source Accession
1 Glycine, serine and threonine metabolism hsa00260
2 Vitamin B6 metabolism hsa00750

GO Terms for Neu-Laxova Syndrome 1

Biological processes related to Neu-Laxova Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular amino acid biosynthetic process GO:0008652 8.96 PHGDH PSAT1
2 L-serine biosynthetic process GO:0006564 8.62 PHGDH PSAT1

Sources for Neu-Laxova Syndrome 1

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
Content
Loading form....