NLS1
MCID: NLX004
MIFTS: 46

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 57 12 75 29 6
Neu-Laxova Syndrome 57 59 37 29 40 73
Neu Laxova Syndrome 76 53
Nls1 57 75
Nls 57 53
3-Phosphoglycerate Dehydrogenase Deficiency, Neonatal Form 59
Neu-Laxova Syndrome; Nls 57

Characteristics:

Orphanet epidemiological data:

59
neu-laxova syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal; Age of death: infantile,stillbirth;

OMIM:

57
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:

32
neu-laxova syndrome 1:
Mortality/Aging stillbirth
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Neu-Laxova Syndrome 1

NIH Rare Diseases : 53 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 Dopamine and Mazindol have been mentioned in the context of this disorder. Affiliated tissues include lung, skin and eye, and related phenotypes are hypertelorism and osteopenia

OMIM : 57 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 : 75 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 : 76 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

Symptoms via clinical synopsis from OMIM:

57
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
lissencephaly
hydranencephaly
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

Human phenotypes related to Neu-Laxova Syndrome 1:

59 32 (show top 50) (show all 94)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 frequent (33%) Frequent (79-30%) HP:0000316
2 osteopenia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000938
3 cerebral calcification 59 32 occasional (7.5%) Occasional (29-5%) HP:0002514
4 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
5 macrotia 59 32 frequent (33%) Frequent (79-30%) HP:0000400
6 cataract 59 32 occasional (7.5%) Occasional (29-5%) HP:0000518
7 thick vermilion border 59 32 hallmark (90%) Very frequent (99-80%) HP:0012471
8 microcephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000252
9 ichthyosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0008064
10 rickets 59 32 occasional (7.5%) Occasional (29-5%) HP:0002748
11 osteoporosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000939
12 skeletal muscle atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0003202
13 cleft palate 59 32 Occasional (29-5%) HP:0000175
14 micrognathia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000347
15 retrognathia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000278
16 micromelia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002983
17 lack of skin elasticity 59 32 hallmark (90%) Very frequent (99-80%) HP:0100679
18 everted lower lip vermilion 59 32 frequent (33%) Frequent (79-30%) HP:0000232
19 prominent occiput 59 32 occasional (7.5%) Occasional (29-5%) HP:0000269
20 intrauterine growth retardation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001511
21 arthrogryposis multiplex congenita 59 32 occasional (7.5%) Occasional (29-5%) HP:0002804
22 hypogonadism 59 32 frequent (33%) Frequent (79-30%) HP:0000135
23 cerebellar hypoplasia 59 32 frequent (33%) Frequent (79-30%) HP:0001321
24 depressed nasal ridge 59 32 frequent (33%) Frequent (79-30%) HP:0000457
25 muscle cramps 59 32 frequent (33%) Frequent (79-30%) HP:0003394
26 polyhydramnios 59 32 frequent (33%) Frequent (79-30%) HP:0001561
27 spina bifida 59 32 occasional (7.5%) Occasional (29-5%) HP:0002414
28 osteomalacia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002749
29 proptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000520
30 absent septum pellucidum 59 32 frequent (33%) Frequent (79-30%) HP:0001331
31 decreased fetal movement 59 32 frequent (33%) Frequent (79-30%) HP:0001558
32 ambiguous genitalia 59 32 frequent (33%) Frequent (79-30%) HP:0000062
33 trismus 59 32 frequent (33%) Frequent (79-30%) HP:0000211
34 pachygyria 59 32 frequent (33%) Frequent (79-30%) HP:0001302
35 polymicrogyria 59 32 frequent (33%) Frequent (79-30%) HP:0002126
36 large hands 59 32 frequent (33%) Frequent (79-30%) HP:0001176
37 sloping forehead 59 32 hallmark (90%) Very frequent (99-80%) HP:0000340
38 dandy-walker malformation 59 32 frequent (33%) Frequent (79-30%) HP:0001305
39 muscular dystrophy 59 32 frequent (33%) Frequent (79-30%) HP:0003560
40 lissencephaly 59 32 Frequent (79-30%) HP:0001339
41 bifid uvula 59 32 occasional (7.5%) Occasional (29-5%) HP:0000193
42 pulmonary hypoplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002089
43 pterygium 59 32 occasional (7.5%) Occasional (29-5%) HP:0001059
44 abnormality of cardiovascular system morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0030680
45 broad foot 59 32 frequent (33%) Frequent (79-30%) HP:0001769
46 abnormality of the philtrum 59 32 frequent (33%) Frequent (79-30%) HP:0000288
47 submucous cleft hard palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000176
48 opisthotonus 59 32 frequent (33%) Frequent (79-30%) HP:0002179
49 aplasia/hypoplasia involving the skeletal musculature 59 32 frequent (33%) Frequent (79-30%) HP:0001460
50 external genital hypoplasia 59 32 frequent (33%) Frequent (79-30%) HP:0003241

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
Dopamine Approved Phase 2 51-61-6, 62-31-7 681
2
Mazindol Approved, Investigational Phase 2 22232-71-9 4020
3 Neurotransmitter Agents Phase 2
4 Neurotransmitter Uptake Inhibitors Phase 2
5 Adrenergic Agents Phase 2
6 Dopamine Uptake Inhibitors Phase 2
7 Dopamine Agents Phase 2
8 Central Nervous System Stimulants 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 29
2 Neu-Laxova Syndrome 1 29 PHGDH

Anatomical Context for Neu-Laxova Syndrome 1

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

41
Lung, Skin, Eye, Brain, Kidney, Heart, Testes

Publications for Neu-Laxova Syndrome 1

Articles related to Neu-Laxova Syndrome 1:

(show top 50) (show all 60)
# Title Authors Year
1
A New Case of Neu-Laxova Syndrome: Infant with Facial Dysmorphism, Arthrogryposis, Ichthyosis, and Microcephalia. ( 29862217 )
2018
2
Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency. ( 30348640 )
2018
3
Neu-Laxova Syndrome: An Unusual Association with Kyphosis. ( 28272663 )
2018
4
Prenatal genetic diagnosis of Neu-Laxova syndrome. ( 28903583 )
2018
5
[Neu-Laxova syndrome: Three case reports and a review of the literature]. ( 27475004 )
2016
6
Identification of a premature stop codon mutation in the PHGDH gene in severe Neu-Laxova syndrome-evidence for phenotypic variability. ( 25913727 )
2015
7
Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. ( 25152457 )
2014
8
Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH. ( 24836451 )
2014
9
Neu-Laxova syndrome: a case report. ( 24584393 )
2014
10
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
11
Rare manifestations of Neu-Laxova syndrome. ( 22233503 )
2012
12
Neu-Laxova syndrome: a prenatal diagnosis. ( 22268252 )
2011
13
Prenatal diagnosis and postmortem findings of Neu-laxova syndrome. ( 24591943 )
2010
14
Neu-Laxova syndrome: A new patient with detailed antenatal and post-natal findings. ( 21108408 )
2010
15
A spectrum of phenotypical expression OF Neu-Laxova syndrome: Three case reports and a review of the literature. ( 20334486 )
2010
16
Neu-Laxova syndrome in an appropriate for gestational age newborn. ( 19052411 )
2008
17
Neu-Laxova syndrome, grossly appearing normal on 20 weeks ultrasonographic scan, that manifested late in pregnancy: a case report. ( 17406877 )
2007
18
A rare cause of polyhydramnios: Neu-Laxova syndrome. ( 16923700 )
2006
19
Neu-Laxova syndrome: a case report and review of the literature. ( 16987270 )
2006
20
Evaluation of a fetus with Neu-Laxova syndrome through prenatal, clinical, and pathological findings. ( 15824491 )
2005
21
Neu-Laxova syndrome: detailed prenatal diagnostic and post-mortem findings and literature review. ( 14994231 )
2004
22
Lethal arthrogryposis with icthyosis: overlap with Neu-Laxova syndrome, restrictive dermopathy and harlequin fetus. ( 15057131 )
2004
23
Neu-Laxova syndrome: a case report. ( 12558841 )
2003
24
What syndrome is this? Neu-Laxova syndrome. ( 12558853 )
2003
25
Second trimester diagnosis of Neu Laxova syndrome. ( 12533807 )
2003
26
Prenatal diagnosis of Neu-Laxova syndrome: a case report. ( 11895570 )
2002
27
Early second trimester prenatal diagnosis of Neu-Laxova syndrome. ( 11857616 )
2002
28
Cerebro-osseous-digital syndrome: four new cases of a lethal skeletal dysplasia--distinct from Neu-Laxova Syndrome. ( 11977163 )
2002
29
Early ultrasound diagnosis of Neu-Laxova syndrome. ( 11494295 )
2001
30
Prenatal sonographic diagnosis of Neu-Laxova syndrome. ( 11745866 )
2001
31
Neu-Laxova syndrome. ( 10713860 )
1999
32
A Japanese case of Neu-Laxova syndrome. ( 9575678 )
1998
33
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
34
Qualitative analysis of fetal movement patterns in the Neu-Laxova syndrome. ( 8843479 )
1996
35
Neu-Laxova syndrome: pathological evaluation of a fetus and review of the literature. ( 8736598 )
1995
36
New manifestations in an infant with Neu Laxova syndrome. ( 7625453 )
1995
37
Sonographic diagnosis of Neu-Laxova syndrome. ( 8294578 )
1994
38
Fetal ultrasonographic detection of hypodontia in the Neu-Laxova syndrome. ( 8227398 )
1993
39
Disorder of cerebellar foliation in Walker's lissencephaly and neu-laxova syndrome. ( 8229082 )
1993
40
Neu-Laxova syndrome: report of a case from Turkey. ( 8375108 )
1993
41
Neu-Laxova syndrome: prenatal ultrasonographic diagnosis, clinical and pathological studies, and new manifestations. ( 1605256 )
1992
42
Echographic, radiological and anatomo-pathological evaluation of a foetus with Neu-Laxova syndrome. ( 1632748 )
1992
43
Neu Laxova syndrome in two Egyptian families. ( 1951459 )
1991
44
New manifestations of Neu-Laxova syndrome. ( 2405670 )
1990
45
Neu-Laxova syndrome: pathological, radiological, and prenatal findings in a stillborn female. ( 2650548 )
1989
46
Neu-Laxova syndrome: a case report. ( 3348318 )
1988
47
Cerebral abnormalities in the Neu-Laxova syndrome. ( 3055985 )
1988
48
The Neu-Laxova syndrome in female sibs: clinical and pathological features with prenatal diagnosis in the second sib. ( 3300330 )
1987
49
A case of the Neu-Laxova syndrome: prenatal ultrasonographic monitoring in the third trimester and the histopathological findings. ( 3544847 )
1987
50
Neu-Laxova syndrome: report of a case and comments. ( 3314507 )
1987

Variations for Neu-Laxova Syndrome 1

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

75
# 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 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 PHGDH NM_006623.3(PHGDH): c.403C> T (p.Arg135Trp) single nucleotide variant Uncertain significance rs267606949 GRCh37 Chromosome 1, 120269520: 120269520
2 PHGDH NM_006623.3(PHGDH): c.403C> T (p.Arg135Trp) single nucleotide variant Uncertain significance rs267606949 GRCh38 Chromosome 1, 119726897: 119726897
3 PHGDH NM_006623.3(PHGDH): c.781G> A (p.Val261Met) single nucleotide variant Likely pathogenic rs267606947 GRCh37 Chromosome 1, 120278055: 120278055
4 PHGDH NM_006623.3(PHGDH): c.781G> A (p.Val261Met) single nucleotide variant Likely pathogenic rs267606947 GRCh38 Chromosome 1, 119735432: 119735432
5 PHGDH NM_006623.3(PHGDH): c.418G> A (p.Gly140Arg) single nucleotide variant Pathogenic/Likely pathogenic rs587777770 GRCh38 Chromosome 1, 119727010: 119727010
6 PHGDH NM_006623.3(PHGDH): c.418G> A (p.Gly140Arg) single nucleotide variant Pathogenic/Likely pathogenic rs587777770 GRCh37 Chromosome 1, 120269633: 120269633
7 PHGDH NM_006623.3(PHGDH): c.488G> A (p.Arg163Gln) single nucleotide variant Uncertain significance rs587777483 GRCh37 Chromosome 1, 120269703: 120269703
8 PHGDH NM_006623.3(PHGDH): c.488G> A (p.Arg163Gln) single nucleotide variant Uncertain significance rs587777483 GRCh38 Chromosome 1, 119727080: 119727080
9 PHGDH NM_006623.3(PHGDH): c.793G> A (p.Glu265Lys) single nucleotide variant Pathogenic rs587777774 GRCh37 Chromosome 1, 120279737: 120279737
10 PHGDH NM_006623.3(PHGDH): c.793G> A (p.Glu265Lys) single nucleotide variant Pathogenic rs587777774 GRCh38 Chromosome 1, 119737114: 119737114
11 PHGDH NM_006623.3(PHGDH): c.856G> C (p.Ala286Pro) single nucleotide variant Pathogenic rs587777775 GRCh37 Chromosome 1, 120279800: 120279800
12 PHGDH NM_006623.3(PHGDH): c.856G> C (p.Ala286Pro) single nucleotide variant Pathogenic rs587777775 GRCh38 Chromosome 1, 119737177: 119737177
13 PHGDH NM_006623.3(PHGDH): c.1030C> T (p.Arg344Ter) single nucleotide variant Pathogenic rs769256568 GRCh38 Chromosome 1, 119740470: 119740470
14 PHGDH NM_006623.3(PHGDH): c.1030C> T (p.Arg344Ter) single nucleotide variant Pathogenic rs769256568 GRCh37 Chromosome 1, 120283093: 120283093

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:

37
# 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

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