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PHS
MCID: PLL001
MIFTS: 66

Pallister-Hall Syndrome (PHS)

Categories: Bone diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Pallister-Hall Syndrome

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MalaCards integrated aliases for Pallister-Hall Syndrome:

Name: Pallister-Hall Syndrome 57 11 19 19 42 58 75 73 28 12 53 5 43 14 38 71
Hypothalamic Hamartomas 19 75 5 71
Phs 57 19 42 73
Hypothalamic Hamartoblastoma, Hypopituitarism, Imperforate Anus, and Postaxial Polydactyly 57 19
Hypothalamic Hamartoblastoma Syndrome 58 75
Hypothalamic Hamartoblastoma Hypopituitarism Imperforate Anus and Postaxial Polydactyly 73
Hamartoma of the Hypothalamus 19
Pallister Hall Syndrome 19
Hall-Pallister Syndrome 42
Hamartoma, Hypothalamic 38

Characteristics:


Inheritance:

Autosomal dominant 58 57

Prevelance:

<1/1000000 (Worldwide) 58

Age Of Onset:

Infancy,Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable expressivity
variable severity


HPO:

30
pallister-hall syndrome:
Onset and clinical course variable expressivity


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Neuronal diseases Nephrological diseases Bone diseases Endocrine diseases
See all MalaCards categories (disease lists)
ICD10: 32
Orphanet: 58  
Rare neurological diseases
Rare renal diseases
Rare bone diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Sources

Summaries for Pallister-Hall Syndrome

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GARD: 19 Hypothalamic hamartomas (HH) are rare, tumor-like malformations that occur during fetal development and are present at birth. The lesions usually do not change in size or spread to other locations. Both the type and severity of symptoms vary greatly among patients with Hypothalamic hamartomas. Common symptoms include frequent gelastic seizures (spontaneous laughing, giggling and/or smirking) or dacrystic seizures (crying or grunting); developmental delays; and/or precocious puberty. Additional symptoms may include cognitive impairment; emotional and behavioral difficulties; and endocrine disturbances. These symptoms often start early in life but are frequently misdiagnosed. For some patients, endocrine (hormonal) disturbances such as central precocious puberty may be the only symptom. Though Hypothalamic hamartomas can occur in patients with certain genetic disorders (such as Pallister-Hall syndrome), the majority of cases are sporadic.

MalaCards based summary: Pallister-Hall Syndrome, also known as hypothalamic hamartomas, is related to culler-jones syndrome and polydactyly, postaxial, type a1. An important gene associated with Pallister-Hall Syndrome is GLI3 (GLI Family Zinc Finger 3), and among its related pathways/superpathways are Signal Transduction and G-Beta Gamma Signaling. Affiliated tissues include hypothalamus, pituitary and bone, and related phenotypes are hypothalamic hamartoma and macrocephaly

MedlinePlus Genetics: 42 Pallister-Hall syndrome is a disorder that affects the development of many parts of the body. Most people with this condition have extra fingers and/or toes (polydactyly), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the brain called a hypothalamic hamartoma is characteristic of this disorder. In many cases, these growths do not cause any health problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister-Hall syndrome include a malformation of the airway called a bifid epiglottis, an obstruction of the anal opening (imperforate anus), and kidney abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications.

UniProtKB/Swiss-Prot: 73 An autosomal dominant disorder characterized by a wide range of clinical manifestations. Clinical features include hypothalamic hamartoma, pituitary dysfunction, central or postaxial polydactyly, and syndactyly. Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia.

Orphanet: 58 Pallister-Hall syndrome (PHS), a pleiotropic autosomal dominant malformative disorder, is characterized by hypothalamic hamartoma, pituitary dysfunction, bifid epiglottis, polydactyly, and, more rarely, renal abnormalities and genitourinary malformations.

Disease Ontology: 11 A syndrome that is characterized by hypothalamic hamartoma, pituitary dysfunction, central polydactyly, and visceral malformations and has material basis in autosomal dominant heterozygous mutation in the GLI3 gene on chromosome 7p14.

OMIM®: 57 Pallister-Hall syndrome is a pleiotropic autosomal dominant disorder comprising hypothalamic hamartoma, pituitary dysfunction, central polydactyly, and visceral malformations (Biesecker et al., 1996). (146510) (Updated 08-Dec-2022)

Wikipedia 75 Hypothalamic hamartoblastoma syndrome: Pallister-Hall syndrome (abbreviated PHS) is a disorder that affects the development of many parts of... more...

Hypothalamic hamartomas: Tuber cinereum hamartoma is a benign tumor in which a disorganized collection of neurons and glia... more...
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Related Diseases for Pallister-Hall Syndrome

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Diseases in the Pallister-Hall Syndrome family:

Pallister-Hall-Like Syndrome Gli3-Related Pallister-Hall Syndrome

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

(show top 50) (show all 269)
# Related Disease Score Top Affiliating Genes
1 culler-jones syndrome 32.3 SIX3 SHH KIF7 IHH GLI3 GLI2
2 polydactyly, postaxial, type a1 31.4 PTCH1 GLI3 GLI1
3 hypopituitarism 31.2 SIX3 SHH GLI2
4 polydactyly 31.0 ZIC2 SIX3 SHH PTCH1 KIF7 IFT27
5 anus, imperforate 30.9 SHH SALL1 IFT27 HOXD13 GLI3 GLI2
6 vater/vacterl association 30.6 HOXD13 FOXF1
7 hypospadias 30.5 SHH HOXD13 FGF8
8 smith-lemli-opitz syndrome 30.5 ZIC2 SIX3 SHH
9 holoprosencephaly 1 30.5 ZIC2 SIX3 SHH FGF8
10 cryptorchidism, unilateral or bilateral 30.4 SHH GLI3 FGF8 DHH
11 hirschsprung disease 1 30.4 SMO SHH PTCH1 IHH GLI3
12 brachydactyly 30.4 SHH PTCH1 IHH HOXD13 GLI1
13 cleft palate, isolated 30.2 SHH PTCH1 IHH GLI3 GLI2 GLI1
14 synostosis 30.2 ZP2 SHH IHH HOXD13 GLI3 FGF8
15 chromosome 2q35 duplication syndrome 30.1 ZP2 SHH SALL1 PTCH1 IHH HOXD13
16 greig cephalopolysyndactyly syndrome 29.9 ZP2 SHH PTCH1 KIF7 IHH HOXD13
17 vacterl association 29.8 ZIC2 SHH SALL1 HOXD13 GLI3 GLI2
18 holoprosencephaly 29.5 ZIC2 SMO SIX3 SHH PTCH1 IHH
19 hypothalamic hamartomas with gelastic seizures 11.6
20 pallister-hall-like syndrome 11.4
21 gli3-related pallister-hall syndrome 11.3
22 hyperphenylalaninemia, bh4-deficient, d 11.1
23 pitt-hopkins syndrome 11.0
24 epilepsy 10.7
25 precocious puberty 10.6
26 renal dysplasia 10.5
27 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 10.5
28 polydactyly, preaxial iv 10.5
29 central polydactyly 10.5
30 vaginal atresia 10.4
31 fibroepithelial basal cell carcinoma 10.3 PTCH1 GLI1
32 central diabetes insipidus 10.3
33 diabetes insipidus 10.3
34 corpus callosum lipoma 10.3 ZIC2 SIX3
35 polydactyly, preaxial ii 10.3 SHH PTCH1
36 large cell medulloblastoma 10.3 SHH PTCH1 GLI2
37 cerebral hemisphere lipoma 10.3 ZIC2 SIX3
38 medullomyoblastoma 10.3 SMO SHH
39 holoprosencephaly, recurrent infections, and monocytosis 10.3 SIX3 PTCH1 GLI2
40 adult medulloblastoma 10.3 SHH PTCH1 GLI2
41 cerebellar medulloblastoma 10.3 SHH PTCH1 GLI1
42 micronodular basal cell carcinoma 10.3 SHH PTCH1 GLI2
43 mckusick-kaufman syndrome 10.3
44 pituitary hormone deficiency, combined, 2 10.3
45 pseudovaginal perineoscrotal hypospadias 10.3
46 premature ovarian failure 7 10.3
47 pituitary gland disease 10.3
48 growth hormone deficiency 10.3
49 laryngeal cleft 10.3
50 joubert syndrome 8 10.3 SHH PTCH1 GLI2

Graphical network of the top 20 diseases related to Pallister-Hall Syndrome:



Diseases related to Pallister-Hall Syndrome
Sources

Symptoms & Phenotypes for Pallister-Hall Syndrome

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Human phenotypes related to Pallister-Hall Syndrome:

58 30 (show top 50) (show all 123)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypothalamic hamartoma 58 30 Very rare (1%) Obligate (100%)
 HP:0002444
2 macrocephaly 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000256
3 ptosis 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000508
4 skeletal dysplasia 58 30 Frequent (33%) Frequent (79-30%)
 HP:0002652
5 hypertelorism 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000316
6 short nose 58 30 Frequent (33%) Frequent (79-30%)
 HP:0003196
7 microtia 58 30 Very rare (1%) Frequent (79-30%)
 HP:0008551
8 anteverted nares 58 30 Occasional (7.5%) Frequent (79-30%)
 HP:0000463
9 short stature 58 30 Frequent (33%) Frequent (79-30%)
 HP:0004322
10 broad thumb 58 30 Frequent (33%) Frequent (79-30%)
 HP:0011304
11 intrauterine growth retardation 58 30 Frequent (33%) Frequent (79-30%)
 HP:0001511
12 short 4th metacarpal 58 30 Occasional (7.5%) Frequent (79-30%)
 HP:0010044
13 downslanted palpebral fissures 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000494
14 depressed nasal ridge 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000457
15 brachydactyly 58 30 Frequent (33%) Frequent (79-30%)
 HP:0001156
16 anal atresia 58 30 Very rare (1%) Frequent (79-30%)
 HP:0002023
17 low-set, posteriorly rotated ears 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000368
18 microphthalmia 58 30 Very rare (1%) Frequent (79-30%)
 HP:0000568
19 hemivertebrae 58 30 Very rare (1%) Frequent (79-30%)
 HP:0002937
20 hip dislocation 58 30 Frequent (33%) Frequent (79-30%)
 HP:0002827
21 rib fusion 58 30 Very rare (1%) Frequent (79-30%)
 HP:0000902
22 toe syndactyly 58 30 Occasional (7.5%) Frequent (79-30%)
 HP:0001770
23 atresia of the external auditory canal 58 30 Very rare (1%) Frequent (79-30%)
 HP:0000413
24 nail dysplasia 58 30 Frequent (33%) Frequent (79-30%)
 HP:0002164
25 bifid uvula 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000193
26 accessory oral frenulum 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000191
27 radial bowing 58 30 Frequent (33%) Frequent (79-30%)
 HP:0002986
28 renal dysplasia 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000110
29 pituitary hypothyroidism 58 30 Frequent (33%) Frequent (79-30%)
 HP:0008245
30 adrenocorticotropic hormone deficiency 58 30 Frequent (33%) Frequent (79-30%)
 HP:0011748
31 laryngeal cleft 58 30 Frequent (33%) Frequent (79-30%)
 HP:0008751
32 natal tooth 58 30 Occasional (7.5%) Frequent (79-30%)
 HP:0000695
33 radial head subluxation 58 30 Frequent (33%) Frequent (79-30%)
 HP:0003048
34 secondary growth hormone deficiency 58 30 Frequent (33%) Frequent (79-30%)
 HP:0008240
35 central adrenal insufficiency 58 30 Frequent (33%) Frequent (79-30%)
 HP:0011734
36 abnormal basal ganglia mri signal intensity 58 30 Frequent (33%) Frequent (79-30%)
 HP:0012751
37 gonadotropin deficiency 58 30 Frequent (33%) Frequent (79-30%)
 HP:0008213
38 abnormal prolactin level 58 30 Frequent (33%) Frequent (79-30%)
 HP:0040086
39 supernumerary metacarpal bones 58 30 Frequent (33%) Frequent (79-30%)
 HP:0005917
40 bilateral postaxial polydactyly 58 30 Frequent (33%) Frequent (79-30%)
 HP:0006136
41 polydactyly affecting the 3rd finger 58 30 Frequent (33%) Frequent (79-30%)
 HP:0009958
42 polydactyly affecting the 4th finger 58 30 Frequent (33%) Frequent (79-30%)
 HP:0009971
43 3-4 finger cutaneous syndactyly 58 30 Frequent (33%) Frequent (79-30%)
 HP:0011939
44 recurrent upper and lower respiratory tract infections 58 30 Frequent (33%) Frequent (79-30%)
 HP:0200117
45 precocious puberty 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000826
46 global developmental delay 58 30 Very rare (1%) Occasional (29-5%)
 HP:0001263
47 inguinal hernia 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000023
48 umbilical hernia 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0001537
49 cryptorchidism 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000028
50 ectopic kidney 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000086

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Head And Neck Nose:
short nose
anteverted nares
flat nasal bridge

Growth Height:
short stature

Growth Other:
intrauterine growth retardation

Head And Neck Eyes:
microphthalmia

Skeletal Spine:
hemivertebrae

Skin Nails Hair Nails:
nail dysplasia

Endocrine Features:
panhypopituitarism
adrenal gland hypoplasia
thyroid dysplasia/aplasia

Skin Nails Hair Skin:
midline facial capillary hemangioma

Genitourinary Kidneys:
renal dysplasia
renal ectopia

Skeletal Limbs:
distal shortening of limbs
radial subluxation

Neurologic Central Nervous System:
hypothalamic hamartoma
holoprosencephaly (less common)
pituitary aplasia or dysplasia

Skeletal Pelvis:
dislocated hips

Head And Neck Teeth:
natal teeth

Head And Neck Ears:
microtia
posteriorly rotated ears
simple auricles
absent external auditory canals

Genitourinary Internal Genitalia Male:
cryptorchidism
testicular hypoplasia

Genitourinary External Genitalia Male:
micropenis

Cardiovascular Vascular:
patent ductus arteriosus

Cardiovascular Heart:
ventricular septal defect
proximal aortic coarctation

Skeletal Hands:
oligodactyly
syndactyly
postaxial polydactyly
short 4th metacarpals

Respiratory Lung:
abnormal lung lobation

Head And Neck Mouth:
microglossia
multiple buccal frenula
cleft lip and palate

Respiratory Larynx:
laryngeal cleft
bifid epiglottis
hypoplastic epiglottis

Skeletal Feet:
syndactyly
postaxial polydactyly

Abdomen Gastrointestinal:
imperforate anus

Chest Ribs Sternum Clavicles And Scapulae:
fused ribs

Clinical features from OMIM®:

146510 (Updated 08-Dec-2022)

MGI Mouse Phenotypes related to Pallister-Hall Syndrome:

45 (show all 19)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.48 ANKUB1 BOC FGF8 FOXF1 GAS1 GLI1
2 nervous system MP:0003631 10.47 BOC DHH FGF8 GAS1 GLI1 GLI2
3 digestive/alimentary MP:0005381 10.43 BOC DHH FGF8 FOXF1 GAS1 GLI1
4 limbs/digits/tail MP:0005371 10.42 BOC FGF8 GAS1 GLI1 GLI2 GLI3
5 embryo MP:0005380 10.42 FGF8 FOXF1 GAS1 GLI1 GLI2 GLI3
6 endocrine/exocrine gland MP:0005379 10.32 DHH FGF8 FOXF1 GLI1 GLI2 GLI3
7 cellular MP:0005384 10.31 FGF8 FOXF1 GAS1 GLI1 GLI2 GLI3
8 craniofacial MP:0005382 10.3 BOC FGF8 GAS1 GLI1 GLI2 GLI3
9 normal MP:0002873 10.28 BOC FGF8 GLI1 GLI2 GLI3 PTCH1
10 respiratory system MP:0005388 10.24 BOC FGF8 FOXF1 GAS1 GLI1 GLI2
11 no phenotypic analysis MP:0003012 10.23 GLI1 GLI2 GLI3 HOXD13 IFT27 IHH
12 cardiovascular system MP:0005385 10.22 ANKUB1 FGF8 FOXF1 GAS1 GLI3 IFT27
13 muscle MP:0005369 10.21 FGF8 FOXF1 GLI2 HOXD13 IHH KIF7
14 skeleton MP:0005390 10.19 ANKUB1 BOC FGF8 GAS1 GLI1 GLI2
15 hearing/vestibular/ear MP:0005377 10.14 FGF8 GAS1 GLI2 GLI3 PTCH1 SALL1
16 reproductive system MP:0005389 10.06 DHH FGF8 GLI1 GLI2 GLI3 HOXD13
17 vision/eye MP:0005391 10 BOC FGF8 GAS1 GLI2 GLI3 HOXD13
18 mortality/aging MP:0010768 9.55 BOC FGF8 FOXF1 GAS1 GLI1 GLI2
19 taste/olfaction MP:0005394 9.26 GLI3 PTCH1 SHH SIX3
Sources

Drugs & Therapeutics for Pallister-Hall Syndrome

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Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Genetic and Clinical Studies of Congenital Anomaly Syndromes Completed NCT00001404

Search NIH Clinical Center for Pallister-Hall Syndrome

Cochrane evidence based reviews: pallister-hall syndrome

Sources

Genetic Tests for Pallister-Hall Syndrome

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Genetic tests related to Pallister-Hall Syndrome:

# Genetic test Affiliating Genes
1 Pallister-Hall Syndrome 28 GLI3
Sources

Anatomical Context for Pallister-Hall Syndrome

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Organs/tissues related to Pallister-Hall Syndrome:

MalaCards : Hypothalamus, Pituitary, Bone, Kidney, Heart, Brain, Skin
Sources

Publications for Pallister-Hall Syndrome

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Articles related to Pallister-Hall Syndrome:

(show top 50) (show all 525)
# Title Authors PMID Year
1
Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations. 53 62 57 5
15739154 2005
2
GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. 53 62 57 5
9054938 1997
3
New insights into genotype-phenotype correlation for GLI3 mutations. 62 57 5
24736735 2015
4
Overlap of PIV syndrome, VACTERL and Pallister-Hall syndrome: clinical and molecular analysis. 62 57 5
10945658 2000
5
Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome. 53 62 57
9192261 1997
6
A familial syndrome of hypothalamic hamartomas, polydactyly, and SMO mutations: a clinical report of 2 cases. 62 5
30497210 2018
7
GLI3-related polydactyly: a review. 62 5
28224613 2017
8
Genital abnormalities in Pallister-Hall syndrome: Report of two patients and review of the literature. 62 57
21108399 2010
9
Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer. 62 5
12545275 2003
10
Long-term treatment with growth hormone improves final height in a patient with Pallister-Hall syndrome. 62 57
11241471 2001
11
Pallister-Hall syndrome with stenosis of the cricoid cartilage and microphallus without hypopituitarism. 62 57
11693785 2001
12
Asymptomatic laryngeal malformations are common in patients with Pallister-Hall syndrome. 62 57
10982485 2000
13
The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A/B; No phenotype prediction from the position of GLI3 mutations. 62 5
10441570 1999
14
[The Pallister-Hall syndrome--a rare case and an example of the differentiated approach to the treatment of hormonally inactive hypothalamic hamartomas]. 62 5
9148633 1997
15
Exclusion of candidate loci and cholesterol biosynthetic abnormalities in familial Pallister-Hall syndrome. 62 57
8950676 1996
16
Report from the workshop on Pallister-Hall syndrome and related phenotypes. 62 57
8914745 1996
17
Polysyndactyly and asymptomatic hypothalamic hamartoma in mother and son: a variant of Pallister-Hall syndrome. 62 57
8591673 1995
18
Stringent delineation of Pallister-Hall syndrome in two long surviving patients: importance of radiological anomalies of the hands. 62 57
7473651 1995
19
Pallister-Hall syndrome and McKusick-Kaufmann syndrome: one entity? 62 57
7760322 1995
20
Syndromal hypothalamic hamartoblastoma with holoprosencephaly sequence, microphthalmia, pulmonary malformations, radial hypoplasia and müllerian regression: further delineation of a new syndrome? 62 57
7735503 1995
21
Autosomal dominant transmission of Pallister-Hall syndrome. 62 57
7894735 1994
22
The Pallister-Hall syndrome. 62 57
7815447 1994
23
Familial Pallister-Hall syndrome: three affected offspring. 62 57
7802025 1994
24
Recurrence of Pallister-Hall syndrome in two sibs. 62 57
8182722 1994
25
Autosomal dominant transmission of the Pallister-Hall syndrome. 62 57
8229528 1993
26
Familial Pallister-Hall syndrome: case report and hormonal evaluation. 62 57
8135274 1993
27
Variability versus heterogeneity in syndromal hypothalamic hamartoblastoma and related disorders: review and delineation of the cerebro-acro-visceral early lethality (CAVE) multiplex syndrome. 62 57
1621756 1992
28
Pallister-Hall syndrome associated with an unbalanced chromosome translocation. 62 57
1605268 1992
29
Extending the Pallister-Hall syndrome to include other central nervous system malformations. 62 57
1746599 1991
30
Case report and delineation of the congenital hypothalamic hamartoblastoma syndrome (Pallister-Hall syndrome). 62 57
2688416 1989
31
Three additional cases of the congenital hypothalamic "hamartoblastoma" (Pallister-Hall) syndrome. 62 57
2596511 1989
32
Smith-Lemli-Opitz syndromes: do they include the Pallister-Hall syndrome? 62 57
3425639 1987
33
Two cases of congenital hypothalamic hamartoblastoma, polydactyly, and other congenital anomalies (Pallister-Hall syndrome) 62 57
7057839 1982
34
Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and postaxial polydactyly--a new syndrome? Part I: clinical, causal, and pathogenetic considerations. 62 57
7211952 1980
35
Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly--a new syndrome? Part II: Neuropathological considerations. 62 57
7211954 1980
36
Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling. 5
32413283 2020
37
Nonsense-mediated decay and the molecular pathogenesis of mutations in SALL1 and GLI3. 5
18000979 2007
38
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. 5
17576681 2007
39
Splicing in action: assessing disease causing sequence changes. 5
16199547 2005
40
Statistical features of human exons and their flanking regions. 5
9536098 1998
41
Pallister-Hall and McKusick-Kaufmann syndromes. 57
7473667 1995
42
Numerical syndromology: a mathematical approach to the nosology of complex phenotypes. 57
7762583 1995
43
The McKusick-Kaufman syndrome: phenotypic variation observed in familial cases as a clue for the evaluation of sporadic cases. 57
7811428 1994
44
A new polydactyly/imperforate-anus/vertebral-anomalies syndrome? 57
4175523 1968
45
Giant diencephalic harmartoma and related anomalies: a newly recognized entity distinct from the Pallister-Hall syndrome. 53 62
19449422 2009
46
Hydrometrocolpos, postaxial polydactyly, and hypothalamic hamartoma in a patient with confirmed Pallister-Hall syndrome: a clinical overlap with McKusick-Kaufman syndrome. 53 62
18478223 2008
47
Identification of somatic chromosomal abnormalities in hypothalamic hamartoma tissue at the GLI3 locus. 53 62
18252217 2008
48
A novel syndrome of cerebral cavernous malformation and Greig cephalopolysyndactyly. Laboratory investigation. 53 62
18154020 2007
49
The molecular basis of Pallister Hall associated polydactyly. 53 62
17588959 2007
50
Pallister-Hall syndrome: unreported skeletal features of a GLI3 mutation. 53 62
16007608 2005
Sources

Variations for Pallister-Hall Syndrome

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ClinVar genetic disease variations for Pallister-Hall Syndrome:

5 (show top 50) (show all 436)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GLI3 NM_000168.6(GLI3):c.2023del (p.Glu675fs) DEL Pathogenic
 13814 rs116840744 GRCh37: 7:42012016-42012016
GRCh38: 7:41972417-41972417
2 GLI3 NM_000168.6(GLI3):c.2012del (p.Gly671fs) DEL Pathogenic
 13815 rs116840743 GRCh37: 7:42012027-42012027
GRCh38: 7:41972428-41972428
3 GLI3 NM_000168.6(GLI3):c.3439G>T (p.Glu1147Ter) SNV Pathogenic
 13818 rs116840768 GRCh37: 7:42005232-42005232
GRCh38: 7:41965634-41965634
4 GLI3 NM_000168.5(GLI3):c.2770_2771insNC_012920.1:g.12243..12314 INSERT Pathogenic
 13823 GRCh37: 7:42005900-42005901
GRCh38: 7:41966302-41966303
5 GLI3 NM_000168.6(GLI3):c.2188_2206del (p.Leu730fs) DEL Pathogenic
 13829 rs116840754 GRCh37: 7:42007419-42007437
GRCh38: 7:41967821-41967839
6 GLI3 NM_000168.6(GLI3):c.3904_3912delinsT (p.Asn1302fs) INDEL Pathogenic
 577666 rs1562657560 GRCh37: 7:42004759-42004767
GRCh38: 7:41965161-41965169
7 GLI3 NM_000168.6(GLI3):c.1778del (p.Arg593fs) DEL Pathogenic
 642780 rs1583747773 GRCh37: 7:42017191-42017191
GRCh38: 7:41977592-41977592
8 SMO NM_005631.5(SMO):c.2291_2292del (p.Gln764fs) DEL Pathogenic
 975032 rs1157132860 GRCh37: 7:128852219-128852220
GRCh38: 7:129212378-129212379
9 SMO NM_005631.5(SMO):c.781C>T (p.Arg261Cys) SNV Pathogenic
 975033 rs755698791 GRCh37: 7:128845484-128845484
GRCh38: 7:129205643-129205643
10 SMO NM_005631.5(SMO):c.1339G>T (p.Glu447Ter) SNV Pathogenic
 975034 rs1006687669 GRCh37: 7:128848674-128848674
GRCh38: 7:129208833-129208833
11 SMO NM_005631.5(SMO):c.1727G>A (p.Arg576Gln) SNV Pathogenic
 975035 rs577512487 GRCh37: 7:128850880-128850880
GRCh38: 7:129211039-129211039
12 SMO NM_005631.5(SMO):c.1726C>T (p.Arg576Trp) SNV Pathogenic
 975036 rs767688088 GRCh37: 7:128850879-128850879
GRCh38: 7:129211038-129211038
13 SMO NM_005631.5(SMO):c.1285A>T (p.Ile429Phe) SNV Pathogenic
 975037 rs1793814652 GRCh37: 7:128848620-128848620
GRCh38: 7:129208779-129208779
14 GLI3 NM_000168.6(GLI3):c.3325G>T (p.Glu1109Ter) SNV Pathogenic
 1320114 GRCh37: 7:42005346-42005346
GRCh38: 7:41965748-41965748
15 GLI3 NM_000168.6(GLI3):c.2598del (p.Ile867fs) DEL Pathogenic
 1320134 GRCh37: 7:42006073-42006073
GRCh38: 7:41966475-41966475
16 GLI3 NM_000168.6(GLI3):c.602_675del (p.Met201fs) DEL Pathogenic
 1358687 GRCh37: 7:42088094-42088167
GRCh38: 7:42048495-42048568
17 GLI3 NM_000168.6(GLI3):c.3956dup (p.Gln1320fs) DUP Pathogenic
 1411219 GRCh37: 7:42004714-42004715
GRCh38: 7:41965116-41965117
18 GLI3 NM_000168.6(GLI3):c.2432-1G>A SNV Pathogenic
 1406215 GRCh37: 7:42006240-42006240
GRCh38: 7:41966642-41966642
19 GLI3 NM_000168.6(GLI3):c.877_881del (p.Thr293fs) DEL Pathogenic
 857479 rs1784103216 GRCh37: 7:42079784-42079788
GRCh38: 7:42040185-42040189
20 GLI3 NM_000168.6(GLI3):c.91G>T (p.Glu31Ter) SNV Pathogenic
 864278 rs1788520333 GRCh37: 7:42262762-42262762
GRCh38: 7:42223163-42223163
21 GLI3 NC_000007.13:g.(?_42187805)_(42262872_?)del DEL Pathogenic
 1070264 GRCh37: 7:42187805-42262872
GRCh38:
22 GLI3 NM_000168.6(GLI3):c.2090del (p.Ala697fs) DEL Pathogenic
 1072899 GRCh37: 7:42011949-42011949
GRCh38: 7:41972350-41972350
23 GLI3 NM_000168.6(GLI3):c.1451G>A (p.Trp484Ter) SNV Pathogenic
 578154 rs1562690271 GRCh37: 7:42063113-42063113
GRCh38: 7:42023514-42023514
24 GLI3 NM_000168.6(GLI3):c.1999C>T (p.Arg667Ter) SNV Pathogenic
 1120233 GRCh37: 7:42012040-42012040
GRCh38: 7:41972441-41972441
25 GLI3 NM_000168.6(GLI3):c.4395del (p.Ser1466fs) DEL Pathogenic
 459213 rs1554304380 GRCh37: 7:42004276-42004276
GRCh38: 7:41964678-41964678
26 GLI3 NM_000168.6(GLI3):c.1878del (p.Lys626fs) DEL Pathogenic
 459207 rs1554306093 GRCh37: 7:42012161-42012161
GRCh38: 7:41972562-41972562
27 GLI3 NM_000168.6(GLI3):c.868C>T (p.Arg290Ter) SNV Pathogenic
 13826 rs121917713 GRCh37: 7:42079797-42079797
GRCh38: 7:42040198-42040198
28 GLI3 NM_000168.6(GLI3):c.4431dup (p.Glu1478Ter) DUP Pathogenic
 376814 rs1057520063 GRCh37: 7:42004239-42004240
GRCh38: 7:41964641-41964642
29 GLI3 NM_000168.6(GLI3):c.3324C>A (p.Tyr1108Ter) SNV Pathogenic
 528800 rs116840766 GRCh37: 7:42005347-42005347
GRCh38: 7:41965749-41965749
30 GLI3 NM_000168.6(GLI3):c.4498G>T (p.Glu1500Ter) SNV Pathogenic
 566915 rs1562656759 GRCh37: 7:42004173-42004173
GRCh38: 7:41964575-41964575
31 GLI3 NM_000168.6(GLI3):c.1433_1434del (p.Ile477_Tyr478insTer) DEL Pathogenic
 651052 rs1583801167 GRCh37: 7:42063130-42063131
GRCh38: 7:42023531-42023532
32 GLI3 NM_000168.6(GLI3):c.753T>G (p.Tyr251Ter) SNV Pathogenic
 645072 rs1583505882 GRCh37: 7:42085056-42085056
GRCh38: 7:42045457-42045457
33 GLI3 NM_000168.6(GLI3):c.885del (p.Ile296fs) DEL Pathogenic
 835724 rs1784103136 GRCh37: 7:42079780-42079780
GRCh38: 7:42040181-42040181
34 GLI3 NM_000168.6(GLI3):c.3784_3787dup (p.Val1263fs) DUP Pathogenic
 844774 rs1787131313 GRCh37: 7:42004883-42004884
GRCh38: 7:41965285-41965286
35 GLI3 NM_000168.6(GLI3):c.3454del (p.Glu1152fs) DEL Pathogenic
 850624 rs1787146494 GRCh37: 7:42005217-42005217
GRCh38: 7:41965619-41965619
36 GLI3 NM_000168.6(GLI3):c.3874del (p.Gln1292fs) DEL Pathogenic
 852063 rs1787127981 GRCh37: 7:42004797-42004797
GRCh38: 7:41965199-41965199
37 GLI3 NC_000007.13:g.(?_42116331)_(42188087_?)del DEL Pathogenic
 1072387 GRCh37: 7:42116331-42188087
GRCh38:
38 GLI3 NM_000168.6(GLI3):c.3365_3366del (p.Val1122fs) DEL Pathogenic
 1075151 GRCh37: 7:42005305-42005306
GRCh38: 7:41965707-41965708
39 GLI3 NM_000168.6(GLI3):c.4316_4724del (p.Tyr1439fs) DEL Pathogenic
 949814 rs1787098071 GRCh37: 7:42003947-42004355
GRCh38: 7:41964349-41964757
40 GLI3 NM_000168.6(GLI3):c.2720del (p.Ser907fs) DEL Pathogenic
 951633 rs1787182897 GRCh37: 7:42005951-42005951
GRCh38: 7:41966353-41966353
41 GLI3 NM_000168.6(GLI3):c.1096C>T (p.Arg366Ter) SNV Pathogenic
 664752 rs1583805203 GRCh37: 7:42065944-42065944
GRCh38: 7:42026345-42026345
42 GLI3 NM_000168.6(GLI3):c.4172del (p.Gly1391fs) DEL Pathogenic
 1120232 GRCh37: 7:42004499-42004499
GRCh38: 7:41964901-41964901
43 GLI3 NM_000168.6(GLI3):c.4507C>T (p.Gln1503Ter) SNV Pathogenic
 1381542 GRCh37: 7:42004164-42004164
GRCh38: 7:41964566-41964566
44 GLI3 NM_000168.6(GLI3):c.3762T>G (p.Tyr1254Ter) SNV Pathogenic
 1425074 GRCh37: 7:42004909-42004909
GRCh38: 7:41965311-41965311
45 GLI3 NM_000168.6(GLI3):c.4413del (p.Thr1472fs) DEL Pathogenic
 1350813 GRCh37: 7:42004258-42004258
GRCh38: 7:41964660-41964660
46 GLI3 NM_000168.6(GLI3):c.2632del (p.Glu878fs) DEL Pathogenic
 1707498 GRCh37: 7:42006039-42006039
GRCh38: 7:41966441-41966441
47 overlap with 16 genes DEL Pathogenic
 1684659 GRCh37:
GRCh38: 16:3619617-4448281
48 GLI3 NM_000168.6(GLI3):c.1874G>A (p.Arg625Gln) SNV Pathogenic
 528805 rs1554306094 GRCh37: 7:42012165-42012165
GRCh38: 7:41972566-41972566
49 GLI3 NM_000168.6(GLI3):c.1497+1G>A SNV Pathogenic
 839677 rs1399654830 GRCh37: 7:42063066-42063066
GRCh38: 7:42023467-42023467
50 GLI3 NM_000168.6(GLI3):c.2374C>T (p.Arg792Ter) SNV Pathogenic
 13828 rs121917714 GRCh37: 7:42007251-42007251
GRCh38: 7:41967653-41967653

Copy number variations for Pallister-Hall Syndrome from CNVD:

6
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 217120 7 1 59900000 Copy number GLI3 Hypothalamic hamartomas
Sources

Expression for Pallister-Hall Syndrome

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Search GEO for disease gene expression data for Pallister-Hall Syndrome.
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Pathways for Pallister-Hall Syndrome

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Pathways related to Pallister-Hall Syndrome according to GeneCards Suite gene sharing:

(show all 24)
# Super pathways Score Top Affiliating Genes
1
Signal Transduction 66
13.72 SMO SHH PTCH1 KIF7 IHH GLI3
2
G-Beta Gamma Signaling 64
Show member pathways
 12.57 SMO PTCH1 GLI3 GLI2 GLI1
3
Presynaptic function of Kainate receptors 66
Show member pathways
 12.36 SMO SHH PTCH1 IHH DHH
4
Wnt / Hedgehog / Notch 3
12.15 SHH PTCH1 GLI2 GLI1
5
Signaling by Hedgehog 66
Show member pathways
 12.11 BOC DHH GAS1 GLI1 GLI2 GLI3
6
Bardet-Biedl syndrome 74
Show member pathways
 12.07 GLI3 IFT27 KIF7 PTCH1 SMO ZIC2
7
Ciliopathies 74
11.96 ZIC2 SMO KIF7 GLI3 GLI2
8
Endochondral ossification 74
Show member pathways
 11.89 PTCH1 IHH GLI3
9
Gastrulation 66
Show member pathways
 11.83 SHH IHH FOXF1
11
RUNX2 regulates bone development 66
Show member pathways
 11.56 IHH GLI3 GLI2
12
Hedgehog signaling pathway 74
11.52 BOC DHH GAS1 GLI1 GLI2 GLI3
13
Development of ureteric collection system 74
11.5 SMO SHH SALL1 GLI3 GLI2 GLI1
14
Genes controlling nephrogenesis 74
11.4 SHH GLI3 FGF8
15
Development_Hedgehog and PTH signaling pathways in bone and cartilage development 22
11.39 GLI1 GLI2 IHH PTCH1 SHH SMO
16
Tumor suppressor activity of SMARCB1 74
Show member pathways
 11.36 SMO PTCH1 GLI3 GLI2 GLI1
17
Hedgehog signaling events mediated by Gli proteins 61
11.31 SMO SHH PTCH1 GLI3 GLI2 GLI1
18
Dopaminergic neurogenesis 74
11.27 SHH GLI2 GLI1 FGF8
19
Alstrom syndrome 74
11.21 SMO PTCH1 IFT27
20
Hair follicle development: organogenesis - part 2 of 3 74
11.2 SMO SHH PTCH1 GLI2 GLI1
21
Signaling events mediated by the Hedgehog family 61
Show member pathways
 10.83 BOC DHH GAS1 GLI2 GLI3 IHH
22
EDA signaling in hair follicle development 74
10.77 GLI1 PTCH1 SHH
23
Tgif disruption of Shh signaling 74
Show member pathways
 10.71 SHH GLI3 FGF8
24
Glypican 3 network 61
10.51 SHH PTCH1
Sources

GO Terms for Pallister-Hall Syndrome

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Cellular components related to Pallister-Hall Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cilium GO:0005929 9.93 SMO PTCH1 KIF7 IFT27 GLI3 GLI2
2 ciliary base GO:0097546 9.73 GLI3 GLI2 GLI1
3 ciliary tip GO:0097542 9.4 SMO KIF7 IFT27 GLI3 GLI2 GLI1
4 GLI-SUFU complex GO:1990788 9.35 GLI3 GLI2 GLI1

Biological processes related to Pallister-Hall Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 107)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 10.69 FOXF1 GLI1 GLI2 GLI3 HOXD13 IHH
2 positive regulation of DNA-templated transcription GO:0045893 10.6 ZIC2 SMO SHH SALL1 PTCH1 GLI3
3 negative regulation of apoptotic process GO:0043066 10.47 FGF8 GLI2 GLI3 IHH SHH SMO
4 positive regulation of cell population proliferation GO:0008284 10.42 SMO SHH IHH GLI2 GLI1 FGF8
5 heart development GO:0007507 10.42 SHH SALL1 GLI3 GLI2 FOXF1 FGF8
6 in utero embryonic development GO:0001701 10.41 SMO PTCH1 IHH GLI3 GLI2 FOXF1
7 regulation of gene expression GO:0010468 10.37 SMO SHH IHH GLI3 DHH
8 central nervous system development GO:0007417 10.32 GLI3 SHH SMO ZIC2
9 osteoblast differentiation GO:0001649 10.32 DHH GLI1 GLI2 GLI3 IHH SMO
10 regulation of cell population proliferation GO:0042127 10.31 SIX3 SHH PTCH1 HOXD13 GLI3
11 heart looping GO:0001947 10.3 FGF8 IHH SHH SMO
12 odontogenesis of dentin-containing tooth GO:0042475 10.29 SMO SHH GLI3 GLI2
13 vasculogenesis GO:0001570 10.26 SMO SHH FOXF1
14 anterior/posterior pattern specification GO:0009952 10.26 GLI2 GLI3 HOXD13 SHH SMO
15 cell fate specification GO:0001708 10.25 DHH IHH SHH SMO
16 kidney development GO:0001822 10.25 SHH SALL1 IFT27 GLI3 GLI2 FGF8
17 positive regulation of protein import into nucleus GO:0042307 10.24 SMO SHH GLI3
18 pituitary gland development GO:0021983 10.24 SIX3 SALL1 GLI2 GLI1
19 neuroblast proliferation GO:0007405 10.23 SMO SHH GLI3
20 metanephros development GO:0001656 10.23 SHH GLI3 FGF8
21 branching involved in blood vessel morphogenesis GO:0001569 10.23 FGF8 IHH SHH
22 hair follicle morphogenesis GO:0031069 10.23 GLI2 SHH SMO
23 liver regeneration GO:0097421 10.22 PTCH1 IHH GLI1
24 pancreas development GO:0031016 10.22 SHH IHH FOXF1
25 positive regulation of neuroblast proliferation GO:0002052 10.21 SMO SHH GLI3
26 protein autoprocessing GO:0016540 10.21 SHH IHH DHH
27 dopaminergic neuron differentiation GO:0071542 10.21 FGF8 SHH SMO
28 proximal/distal pattern formation GO:0009954 10.21 GLI3 GLI2 GLI1
29 branching involved in ureteric bud morphogenesis GO:0001658 10.21 SHH SALL1 PTCH1 GLI3 FGF8
30 regulation of smoothened signaling pathway GO:0008589 10.19 GAS1 GLI1 PTCH1
31 positive regulation of epithelial cell proliferation GO:0050679 10.19 SMO SHH IHH GLI2
32 male genitalia development GO:0030539 10.19 SHH HOXD13 FGF8
33 negative regulation of smoothened signaling pathway GO:0045879 10.19 PTCH1 KIF7 GLI3 GLI2
34 negative regulation of neuron differentiation GO:0045665 10.18 SIX3 SHH GLI3
35 stem cell proliferation GO:0072089 10.18 FGF8 GLI2 GLI3 PTCH1 SHH
36 positive regulation of mesenchymal cell proliferation GO:0002053 10.17 FOXF1 IHH SHH SMO
37 lung development GO:0030324 10.17 FGF8 FOXF1 GLI1 GLI2 GLI3 SHH
38 heart morphogenesis GO:0003007 10.16 SMO PTCH1 FGF8
39 self proteolysis GO:0097264 10.16 DHH IHH SHH
40 positive regulation of T cell differentiation in thymus GO:0033089 10.16 SHH IHH GLI2
41 embryonic digestive tract morphogenesis GO:0048557 10.16 FOXF1 GLI3 IHH SHH
42 embryonic limb morphogenesis GO:0030326 10.15 SHH PTCH1 HOXD13 GLI3
43 positive regulation of alpha-beta T cell differentiation GO:0046638 10.15 GLI3 IHH SHH
44 limb morphogenesis GO:0035108 10.15 FGF8 GLI3 HOXD13 PTCH1
45 cell population proliferation GO:0008283 10.14 SMO SHH IHH GLI3 GLI2 FGF8
46 somite development GO:0061053 10.14 SMO SHH PTCH1 IHH
47 branching morphogenesis of an epithelial tube GO:0048754 10.13 SHH GLI3 GLI2
48 negative regulation of chondrocyte differentiation GO:0032331 10.12 IHH GLI3 GLI2
49 forebrain dorsal/ventral pattern formation GO:0021798 10.12 SIX3 GLI3 FGF8
50 determination of left/right symmetry GO:0007368 10.11 FGF8 FOXF1 SHH SMO

Molecular functions related to Pallister-Hall Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cholesterol-protein transferase activity GO:0140853 9.43 SHH IHH DHH
2 patched binding GO:0005113 9.32 SMO SHH PTCH1 IHH DHH
Sources

Sources for Pallister-Hall Syndrome

About this section
2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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