LPHAS
MCID: ULN017
MIFTS: 35

Ulna and Fibula, Absence of, with Severe Limb Deficiency (LPHAS)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Ulna and Fibula, Absence of, with Severe Limb Deficiency

MalaCards integrated aliases for Ulna and Fibula, Absence of, with Severe Limb Deficiency:

Name: Ulna and Fibula, Absence of, with Severe Limb Deficiency 57 39
Schinzel Phocomelia Syndrome 57 12 20 72 29 6
Aarrs 57 12 20 72
Absence of Ulna and Fibula with Severe Limb Deficiency 12 20 72
Limb/pelvis-Hypoplasia/aplasia Syndrome 57 12 72
Al-Awadi/raas-Rothschild Syndrome 57 72 36
Lphas 57 12 72
Al-Awadi/raas-Rothschild/schinzel Phocomelia Syndrome 12 20
Aplasia/hypoplasia of Limbs and Pelvis 12 58
Congenital Absence of Ulna and Fibula 12 58
Al Awadi-Raas-Rothschild Syndrome 12 58
Phocomelia, Schinzel Type 20 58
Schinzel Type Phocomelia 12 20
Severe Limb Deficit 12 58
Ulna and Fibula, Absence of, with Sever Limb Deficiency 13
Ulna and Fibula Absence of with Severe Limb Deficiency 20
Limb/pelvis-Hypoplasia/aplasia Syndrome; Lphas 57
Limb/pelvis/uterus-Hypoplasia/aplasia Syndrome 72
Al-Awadi/raas-Rothschild Syndrome; Aarrs 57
Limb Pelvis Hypoplasia Aplasia Syndrome 72
Al-Awadi-Raas-Rothschild Syndrome 20

Characteristics:

Orphanet epidemiological data:

58
phocomelia, schinzel type
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
allelic to fibular aplasia or hypoplasia, femoral bowing, and poly-, syn-, and oligodactyly (fuhrmann syndrome, )


HPO:

31
ulna and fibula, absence of, with severe limb deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Ulna and Fibula, Absence of, with Severe Limb Deficiency

GARD : 20 Al-Awadi-Raas-Rothschild (AARR) syndrome is a very rare genetic syndrome characterized by skeletal abnormalities. It is a type of skeletal dysplasia. Signs and symptoms of AARR syndrome are present from birth and may include having no fibula (lower bone of the leg) or ulna (bone of the arm), having an underdeveloped (hypoplastic) pelvis, and having differences in the sex structures ( genitalia ). Females with this syndrome may have an absent uterus, and males may have undescended testes ( cryptorchidism ). Al-Awadi-Raas-Rothschild syndrome is caused by mutations (changes) to the WNT7A gene and is inherited in an autosomal recessive manner. Diagnosis of the syndrome can be made when a doctor observes signs and symptoms consistent with the syndrome. The diagnosis can be confirmed by genetic testing. Treatment for Al-Awadi-Raas-Rothschild syndrome depends on the specific symptoms of each affected person, but may include surgical options. Al-Awadi-Raas-Rothschild syndrome is very similar to another syndrome known as Fuhrmann syndrome. The symptoms associated with Fuhrmann syndrome tend to be more mild than those associated with Al-Awadi-Raas-Rothschild syndrome.

MalaCards based summary : Ulna and Fibula, Absence of, with Severe Limb Deficiency, also known as schinzel phocomelia syndrome, is related to fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly and synostosis. An important gene associated with Ulna and Fibula, Absence of, with Severe Limb Deficiency is WNT7A (Wnt Family Member 7A). Affiliated tissues include uterus, testes and bone, and related phenotypes are abnormality of tibia morphology and micromelia

Disease Ontology : 12 A syndrome characterized by severe malformations of upper and lower limbs,severely hypoplastic pelvis, and abnormal genitalia that has material basis in homozygous or compound heterozygous mutation in WNT7A on chromosome 3p25.1.

OMIM® : 57 The Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome (AARRS) is a rare autosomal recessive disorder characterized by severe malformations of upper and lower limbs with severely hypoplastic pelvis and abnormal genitalia. The disorder is believed to represent a defect of dorsoventral patterning and outgrowth of limbs (summary by Kantaputra et al., 2010). (276820) (Updated 20-May-2021)

KEGG : 36 Al-Awadi/Raas-Rothschild syndrome is a limb malformation disorder that has overlapping phenotype with Fuhrmann syndrome, but more-severe limb truncation is observed. This is due to complete loss of WNT7A function in Al-Awadi/Raas-Rothschild syndrome whereas impairment is partial in Fuhrmann syndrome.

UniProtKB/Swiss-Prot : 72 Limb pelvis hypoplasia aplasia syndrome: A syndrome of severe deficiency of the extremities due to hypo- or aplasia of one or more long bones of one or more limbs. Pelvic manifestations include hip dislocation, hypoplastic iliac bone and aplastic pubic bones. Thoracic deformity, unusual facies and genitourinary anomalies can be present.

Related Diseases for Ulna and Fibula, Absence of, with Severe Limb Deficiency

Diseases related to Ulna and Fibula, Absence of, with Severe Limb Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 19)
# Related Disease Score Top Affiliating Genes
1 fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly 10.6
2 synostosis 10.5
3 phocomelia 10.5
4 breasts and/or nipples, aplasia or hypoplasia of, 1 10.4
5 cleft palate, isolated 10.4
6 humeroradial synostosis 10.4
7 hypertelorism 10.4
8 split-hand/foot malformation 1 10.4
9 taurodontism 10.4
10 tooth agenesis 10.4
11 bladder exstrophy 10.4
12 cleft lip 10.4
13 cleft lip/palate 10.4
14 isolated split hand-split foot malformation 10.4
15 amelia 10.4
16 autosomal recessive disease 10.3
17 osteochondrodysplasia 10.2
18 hydronephrosis 10.1
19 anus, imperforate 9.9

Graphical network of the top 20 diseases related to Ulna and Fibula, Absence of, with Severe Limb Deficiency:



Diseases related to Ulna and Fibula, Absence of, with Severe Limb Deficiency

Symptoms & Phenotypes for Ulna and Fibula, Absence of, with Severe Limb Deficiency

Human phenotypes related to Ulna and Fibula, Absence of, with Severe Limb Deficiency:

58 31 (show top 50) (show all 73)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of tibia morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0002992
2 micromelia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002983
3 nail dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002164
4 ectrodactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0100257
5 disproportionate short stature 58 31 frequent (33%) Very frequent (99-80%) HP:0003498
6 hand oligodactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001180
7 fibular aplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002990
8 aplasia/hypoplasia of the sacrum 58 31 hallmark (90%) Very frequent (99-80%) HP:0008517
9 foot oligodactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001849
10 aplasia/hypoplasia involving the pelvis 58 31 hallmark (90%) Very frequent (99-80%) HP:0009103
11 short foot 31 hallmark (90%) HP:0001773
12 aplasia/hypoplasia of the femur 31 hallmark (90%) HP:0005613
13 aplasia of the ulna 31 hallmark (90%) HP:0003982
14 short neck 58 31 frequent (33%) Frequent (79-30%) HP:0000470
15 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
16 micrognathia 58 31 frequent (33%) Frequent (79-30%) HP:0000347
17 hypoplasia of the radius 58 31 frequent (33%) Frequent (79-30%) HP:0002984
18 aplasia of the uterus 58 31 occasional (7.5%) Frequent (79-30%) HP:0000151
19 radial bowing 58 31 frequent (33%) Frequent (79-30%) HP:0002986
20 humeroradial synostosis 58 31 frequent (33%) Occasional (29-5%) HP:0003041
21 elbow flexion contracture 31 frequent (33%) HP:0002987
22 split hand 31 frequent (33%) HP:0001171
23 phocomelia 31 frequent (33%) HP:0009829
24 aplasia/hypoplasia involving the metacarpal bones 31 frequent (33%) HP:0005914
25 femoral bowing 31 frequent (33%) HP:0002980
26 elbow ankylosis 31 frequent (33%) HP:0003070
27 aplasia/hypoplasia of the phalanges of the hand 31 frequent (33%) HP:0009767
28 aplasia/hypoplasia of the phalanges of the toes 31 frequent (33%) HP:0010173
29 aplasia/hypoplasia of metatarsal bones 31 frequent (33%) HP:0001964
30 aplasia/hypoplasia of the pubic bone 31 frequent (33%) HP:0009104
31 aplasia/hypoplasia involving the carpal bones 31 frequent (33%) HP:0006502
32 aplasia/hypoplasia of the tarsal bones 31 frequent (33%) HP:0008363
33 short nose 58 31 occasional (7.5%) Occasional (29-5%) HP:0003196
34 cleft palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000175
35 hydrops fetalis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001789
36 cryptorchidism 58 31 very rare (1%) Occasional (29-5%) HP:0000028
37 high, narrow palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0002705
38 meningocele 58 31 occasional (7.5%) Occasional (29-5%) HP:0002435
39 anal atresia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002023
40 talipes 58 31 occasional (7.5%) Occasional (29-5%) HP:0001883
41 tracheoesophageal fistula 58 31 occasional (7.5%) Occasional (29-5%) HP:0002575
42 protruding ear 58 31 occasional (7.5%) Occasional (29-5%) HP:0000411
43 hypoplasia of penis 58 31 occasional (7.5%) Occasional (29-5%) HP:0008736
44 hip dislocation 31 occasional (7.5%) HP:0002827
45 occipital meningocele 31 occasional (7.5%) HP:0002436
46 calvarial skull defect 31 occasional (7.5%) HP:0001362
47 broad ribs 31 very rare (1%) HP:0000885
48 broad neck 31 very rare (1%) HP:0000475
49 long face 31 very rare (1%) HP:0000276
50 scrotal hypoplasia 31 very rare (1%) HP:0000046

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Mouth:
high palate
narrow palate

Chest Ribs Sternum Clavicles And Scapulae:
pectus carinatum
broad ribs
prominent sternum
broad clavicles
pseudoarthrosis of clavicle

Head And Neck Ears:
low-set ears
dysplastic ears
long ears

Head And Neck Face:
long face
asymmetric face

Genitourinary External Genitalia Male:
hypospadias
anteriorly displaced genitalia
hypoplastic scrotum

Skeletal Hands:
oligodactyly
ectrodactyly
aplastic/hypoplastic phalanges
aplastic carpal bone
mobile wrist
more
Skin Nails Hair Nails:
anonychia

Chest External Features:
barrel-shaped chest

Skin Nails Hair Skin:
pilonidal sinus

Head And Neck Nose:
broad nasal bridge

Growth Height:
short stature, disproportionate

Skeletal Skull:
poorly ossified calvarium

Head And Neck Neck:
short neck
broad neck

Genitourinary Internal Genitalia Male:
cryptorchidism

Skeletal Spine:
hemivertebrae

Skeletal Pelvis:
hip dislocation
aplastic pubic bones
hypoplastic iliac bone

Chest Breasts:
hypoplastic nipples

Skeletal Feet:
oligodactyly
aplastic/hypoplastic phalanges
aplastic/hypoplastic metatarsals
aplastic/hypoplastic tarsals
hypoplastic feet

Skeletal Limbs:
humeroradial synostosis
elbow flexion contractures
shortened forearm
short, bowed radii
aplastic ulnae
more
Neurologic Central Nervous System:
occipital meningocele

Genitourinary External Genitalia Female:
anteriorly displaced genitalia

Head And Neck Eyes:
epicanthal folds

Genitourinary Internal Genitalia Female:
absent uterus

Clinical features from OMIM®:

276820 (Updated 20-May-2021)

Drugs & Therapeutics for Ulna and Fibula, Absence of, with Severe Limb Deficiency

Search Clinical Trials , NIH Clinical Center for Ulna and Fibula, Absence of, with Severe Limb Deficiency

Genetic Tests for Ulna and Fibula, Absence of, with Severe Limb Deficiency

Genetic tests related to Ulna and Fibula, Absence of, with Severe Limb Deficiency:

# Genetic test Affiliating Genes
1 Schinzel Phocomelia Syndrome 29 WNT7A

Anatomical Context for Ulna and Fibula, Absence of, with Severe Limb Deficiency

MalaCards organs/tissues related to Ulna and Fibula, Absence of, with Severe Limb Deficiency:

40
Uterus, Testes, Bone

Publications for Ulna and Fibula, Absence of, with Severe Limb Deficiency

Articles related to Ulna and Fibula, Absence of, with Severe Limb Deficiency:

(show all 21)
# Title Authors PMID Year
1
A novel homozygous Arg222Trp missense mutation in WNT7A in two sisters with severe Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome. 61 57 6
20949531 2010
2
Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome. 57 6 61
16826533 2006
3
A novel homozygous missense mutation (c.610G>A, p.Gly204Ser) in the WNT7A gene causes tetra-amelia in two Saudi families. 6 57
21344627 2011
4
Al-Awadi-Raas-Rothschild (limb/pelvis/uterus-hypoplasia/aplasia) syndrome and WNT7A mutations: genetic homogeneity and nosological delineation. 57 6
21271649 2011
5
Limb/pelvis hypoplasia/aplasia with skull defect (Schinzel phocomelia): distinctive features and prenatal detection. 57 61
11746009 2001
6
Phocomelia, oligodactyly, and acrania: the Schinzel-Phocomelia syndrome. 61 57
8123061 1993
7
Al-Awadi/Raas-Rothschild/Schinzel (AARRS) phocomelia syndrome: case report and developmental field analysis. 57
19530188 2009
8
Al-Awadi/Raas-Rothschild syndrome: two new cases and review. 57
17431918 2007
9
A newly recognized syndrome involving limbs, pelvis, and genital organs or a variant of Al-Awadi/Raas-Rothschild syndrome? 57
15558579 2005
10
On the nosology of the "Schinzel-phocomelia" and "Al-Awadi/Raas-Rothschield" syndromes. 57
8291563 1993
11
Limb/pelvis/uterus-hypoplasia/aplasia syndrome. 57
8411080 1993
12
Limb/pelvis-hypoplasia/aplasia syndrome (Al-Awadi/Raas-Rothschild syndrome): report of two Italian sibs and further confirmation of autosomal recessive inheritance. 57
8423611 1993
13
The newly recognised limb/pelvis-hypoplasia/aplasia syndrome: report of a Bedouin patient and review. 57
8423610 1993
14
Phocomelia and additional anomalies in two sisters. 57
2338339 1990
15
Pathological features and prenatal diagnosis in the newly recognised limb/pelvis-hypoplasia/aplasia syndrome. 57
3066902 1988
16
Profound limb deficiency, thoracic dystrophy, unusual facies, and normal intelligence: a new syndrome. 57
3981578 1985
17
[Defects of the femur and fibula with amelia, peromelia or ulnar defects of the arm. A syndrome]. 57
6074386 1967
18
Molecular basis of the clinical features of Al-Awadi-Raas-Rothschild (limb/pelvis/uterus-hypoplasia/aplasia) syndrome (AARRS) and Fuhrmann syndrome. 20
23922166 2013
19
A report of two cases of Al-Awadi Raas-Rothschild syndrome (AARRS) supporting that "apparent" Phocomelia differentiates AARRS from Schinzel Phocomelia syndrome (SPS). 61
23727605 2013
20
Prenatal diagnosis of a case with anencephaly-omphalocele-unilateral absent radial ray. 61
19650417 2009
21
Phocomelia, ectrodactyly, skull defect and urinary system anomaly: Schinzel-phocomelia syndrome? 61
8740915 1996

Variations for Ulna and Fibula, Absence of, with Severe Limb Deficiency

ClinVar genetic disease variations for Ulna and Fibula, Absence of, with Severe Limb Deficiency:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 WNT7A NM_004625.4(WNT7A):c.874C>T (p.Arg292Cys) SNV Pathogenic 8060 rs104893835 GRCh37: 3:13860617-13860617
GRCh38: 3:13819120-13819120
2 WNT7A NM_004625.4(WNT7A):c.610G>A (p.Gly204Ser) SNV Pathogenic 35537 rs387907231 GRCh37: 3:13860881-13860881
GRCh38: 3:13819384-13819384
3 WNT7A NM_004625.4(WNT7A):c.664C>T (p.Arg222Trp) SNV Pathogenic 40130 rs397514643 GRCh37: 3:13860827-13860827
GRCh38: 3:13819330-13819330
4 WNT7A NM_004625.4(WNT7A):c.214G>A (p.Glu72Lys) SNV Pathogenic 40302 rs397514666 GRCh37: 3:13916528-13916528
GRCh38: 3:13875031-13875031
5 WNT7A NM_004625.4(WNT7A):c.304C>T (p.Arg102Trp) SNV Pathogenic 253008 rs879255548 GRCh37: 3:13896295-13896295
GRCh38: 3:13854798-13854798

UniProtKB/Swiss-Prot genetic disease variations for Ulna and Fibula, Absence of, with Severe Limb Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 WNT7A p.Arg292Cys VAR_030674 rs104893835
2 WNT7A p.Arg222Trp VAR_064480 rs397514643
3 WNT7A p.Glu72Lys VAR_065765 rs397514666

Expression for Ulna and Fibula, Absence of, with Severe Limb Deficiency

Search GEO for disease gene expression data for Ulna and Fibula, Absence of, with Severe Limb Deficiency.

Pathways for Ulna and Fibula, Absence of, with Severe Limb Deficiency

GO Terms for Ulna and Fibula, Absence of, with Severe Limb Deficiency

Sources for Ulna and Fibula, Absence of, with Severe Limb Deficiency

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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