MCID: GLD006
MIFTS: 47

Goldberg-Shprintzen Syndrome

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Gastrointestinal diseases, Fetal diseases

Aliases & Classifications for Goldberg-Shprintzen Syndrome

MalaCards integrated aliases for Goldberg-Shprintzen Syndrome:

Name: Goldberg-Shprintzen Syndrome 57 12 53 75 15
Goldberg-Shprintzen Megacolon Syndrome 57 12 53 59 75 37 29 13 6 44 40 73
Goshs 57 53 59 75
Megacolon-Microcephaly Syndrome 59

Characteristics:

Orphanet epidemiological data:

59
goldberg-shprintzen megacolon syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
prenatal onset
additional developmental abnormalities may be seen in some patients


HPO:

32
goldberg-shprintzen syndrome:
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Goldberg-Shprintzen Syndrome

OMIM : 57 Goldberg-Shprintzen syndrome is an autosomal recessive multiple congenital anomaly syndrome characterized by intellectual disability, microcephaly, and dysmorphic facial features. Most patients also have Hirschsprung disease and/or gyral abnormalities of the brain, consistent with defects in migration of neural crest cells and neurons. Other features, such as megalocornea or urogenital anomalies, may also be present. Goldberg-Shprintzen syndrome has some resemblance to Mowat-Wilson syndrome (MOWS; 235730) but is genetically distinct (summary by Drevillon et al., 2013). Yomo et al. (1991) referred to this disorder as Goldberg-Shprintzen syndrome, which should not be confused with Shprintzen-Goldberg craniosynostosis syndrome (182212) or 2 other Shprintzen syndromes (192430, 182210). (609460)

MalaCards based summary : Goldberg-Shprintzen Syndrome, also known as goldberg-shprintzen megacolon syndrome, is related to hirschsprung disease 1 and megacolon. An important gene associated with Goldberg-Shprintzen Syndrome is KIF1BP (KIF1 Binding Protein), and among its related pathways/superpathways are Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways and G-protein signaling_H-RAS regulation pathway. Affiliated tissues include eye, brain and heart, and related phenotypes are hypertelorism and finger syndactyly

Disease Ontology : 12 A syndrome characterized by intellectual disability, specific facial gestalt and Hirschsprung's disease (HSCR). It has material basis in homozygous mutation in the KIAA1279 gene on chromosome 10q21.1.

NIH Rare Diseases : 53 Goldberg-Shprintzen megacolon syndrome is a very rare genetic condition characterized by Hirschsprung disease, megacolon, small head, widely spaced eyes, cleft palate, short stature, and learning disability. This condition has been described in about 15 individuals to date. Some of the reported cases also had iris coloboma, hypotonia, epilepsy, and ptosis. One of the described patients had sparse scalp hair, a sloping forehead, sparse eyebrows, broad nasal bridge, large ears, pointed chin, ventricular septal defect, hypospadias, syndactyly between the second and third fingers, and clubfeet. This condition appears to be inherited as an autosomal recessivetrait and was found to be caused by mutations in the KIAA1279 gene.

UniProtKB/Swiss-Prot : 75 Goldberg-Shprintzen syndrome: A disorder characterized by intellectual disability, microcephaly, and dysmorphic facial features. Most patients also have Hirschsprung disease.

Related Diseases for Goldberg-Shprintzen Syndrome

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

(show all 39)
# Related Disease Score Top Affiliating Genes
1 hirschsprung disease 1 30.5 EDN3 EDNRB GDNF RET
2 megacolon 29.9 EDN3 EDNRB GDNF KIF1BP RET
3 mowat-wilson syndrome 11.4
4 waardenburg syndrome type 4 10.7 EDN3 EDNRB
5 medullary sponge kidney 10.6 GDNF RET
6 cochlear disease 10.5 EDN3 EDNRB
7 hypoganglionosis 10.5 GDNF RET
8 waardenburg syndrome, type 4a 10.3 EDN3 EDNRB RET
9 multiple endocrine neoplasia, type iib 10.3 EDNRB GDNF RET
10 microcephaly 10.3
11 waardenburg's syndrome 10.2 EDN3 EDNRB RET
12 thyroid carcinoma, familial medullary 10.2 EDNRB GDNF RET
13 axonal neuropathy 10.2
14 neuropathy 10.2
15 thyroid cancer, nonmedullary, 2 10.2 EDNRB GDNF RET
16 jejunoileitis 10.2 GDNF NGF
17 familial renal papillary carcinoma 10.1 NGF RET
18 ohdo syndrome 10.1 KAT6B MED12
19 cerebellar hypoplasia 10.1
20 ptosis 10.1
21 heart disease 10.1
22 epilepsy 10.1
23 neuronitis 10.1
24 coloboma of iris 10.1
25 pachygyria 10.1
26 hypotonia 10.1
27 multiple endocrine neoplasia, type iia 10.1 GDNF RET
28 phaeochromocytoma 10.1 NGF RET
29 intestinal obstruction 10.0 EDN3 EDNRB GDNF RET
30 constipation 10.0 EDN3 EDNRB GDNF RET
31 meningoencephalitis 10.0 GDNF NGF
32 neuroma 10.0 GDNF NGF RET
33 blepharophimosis 9.9 KAT6B MED12
34 pyloric stenosis 9.8 GDNF RET
35 autonomic nervous system disease 9.7 ASCL1 EDNRB NGF
36 partington x-linked mental retardation syndrome 9.4 ASCL1 STMN1
37 colonic disease 9.3 ASCL1 EDN3 EDNRB GDNF RET
38 central hypoventilation syndrome, congenital 9.2 ASCL1 EDN3 EDNRB GDNF RET
39 pheochromocytoma 9.2 ASCL1 GDNF NGF RET

Graphical network of the top 20 diseases related to Goldberg-Shprintzen Syndrome:



Diseases related to Goldberg-Shprintzen Syndrome

Symptoms & Phenotypes for Goldberg-Shprintzen Syndrome

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears
thick earlobes

Skeletal Hands:
clinodactyly
small hands
tapered fingers

Head And Neck Head:
microcephaly

Head And Neck Face:
short philtrum
maxillary hypoplasia
thick philtrum

Skin Nails Hair Hair:
sparse hair

Chest Breasts:
widely spaced nipples

Abdomen Gastrointestinal:
hirschsprung disease (in most patients)

Head And Neck Neck:
short neck

Head And Neck Eyes:
ptosis
megalocornea
telecanthus
synophrys
blue sclerae
more
Head And Neck Nose:
prominent nasal bridge
broad nasal bridge
bulbous nasal tip

Neurologic Central Nervous System:
pachygyria
polymicrogyria
mental retardation
delayed psychomotor development
thin corpus callosum
more
Muscle Soft Tissue:
hypotonia

Head And Neck Mouth:
everted lower lip
full lips


Clinical features from OMIM:

609460

Human phenotypes related to Goldberg-Shprintzen Syndrome:

59 32 (show all 50)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000316
2 finger syndactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0006101
3 ptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000508
4 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
5 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
6 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
7 macrotia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000400
8 wide nasal bridge 59 32 occasional (7.5%) Occasional (29-5%) HP:0000431
9 microcephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000252
10 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
11 cleft palate 59 32 hallmark (90%) Very frequent (99-80%) HP:0000175
12 specific learning disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001328
13 ventriculomegaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0002119
14 aganglionic megacolon 59 32 hallmark (90%) Very frequent (99-80%) HP:0002251
15 hypospadias 59 32 occasional (7.5%) Occasional (29-5%) HP:0000047
16 sparse scalp hair 59 32 occasional (7.5%) Occasional (29-5%) HP:0002209
17 pointed chin 59 32 occasional (7.5%) Occasional (29-5%) HP:0000307
18 iris coloboma 59 32 frequent (33%) Frequent (79-30%) HP:0000612
19 bifid scrotum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000048
20 pachygyria 59 32 occasional (7.5%) Occasional (29-5%) HP:0001302
21 sloping forehead 59 32 occasional (7.5%) Occasional (29-5%) HP:0000340
22 hypoplasia of the corpus callosum 59 32 occasional (7.5%) Occasional (29-5%) HP:0002079
23 low-set ears 32 HP:0000369
24 short neck 32 HP:0000470
25 clinodactyly 32 HP:0030084
26 global developmental delay 32 HP:0001263
27 thick vermilion border 32 HP:0012471
28 thick eyebrow 32 HP:0000574
29 megalocornea 32 HP:0000485
30 corneal erosion 32 HP:0200020
31 everted lower lip vermilion 32 HP:0000232
32 wide intermamillary distance 32 HP:0006610
33 prominent nasal bridge 32 HP:0000426
34 telecanthus 32 HP:0000506
35 short philtrum 32 HP:0000322
36 small hand 32 HP:0200055
37 hypoplasia of the maxilla 32 HP:0000327
38 downslanted palpebral fissures 32 HP:0000494
39 bulbous nose 32 HP:0000414
40 highly arched eyebrow 32 HP:0002553
41 synophrys 32 HP:0000664
42 blue sclerae 32 HP:0000592
43 polymicrogyria 32 HP:0002126
44 tapered finger 32 HP:0001182
45 sparse hair 32 HP:0008070
46 sparse eyebrow 59 Occasional (29-5%)
47 generalized hypotonia 32 HP:0001290
48 corneal ulceration 32 HP:0012804
49 hypoplasia of the brainstem 32 HP:0002365
50 sparse and thin eyebrow 32 occasional (7.5%) HP:0000535

MGI Mouse Phenotypes related to Goldberg-Shprintzen Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.85 ASCL1 EDN3 EDNRB GDNF KIF18A KIF1A
2 cardiovascular system MP:0005385 9.8 EDNRB GDNF KIF1BP MED12 NGF RET
3 muscle MP:0005369 9.43 EDNRB GDNF KIF1BP NGF RET STMN1
4 nervous system MP:0003631 9.32 KIF1BP MED12 NGF RET STMN1 ASCL1

Drugs & Therapeutics for Goldberg-Shprintzen Syndrome

Search Clinical Trials , NIH Clinical Center for Goldberg-Shprintzen Syndrome

Cochrane evidence based reviews: goldberg-shprintzen megacolon syndrome

Genetic Tests for Goldberg-Shprintzen Syndrome

Genetic tests related to Goldberg-Shprintzen Syndrome:

# Genetic test Affiliating Genes
1 Goldberg-Shprintzen Megacolon Syndrome 29 KIF1BP

Anatomical Context for Goldberg-Shprintzen Syndrome

MalaCards organs/tissues related to Goldberg-Shprintzen Syndrome:

41
Eye, Brain, Heart

Publications for Goldberg-Shprintzen Syndrome

Articles related to Goldberg-Shprintzen Syndrome:

(show all 12)
# Title Authors Year
1
Association of a Novel Nonsense Mutation in KIAA1279 with Goldberg-Shprintzen Syndrome. ( 28277559 )
2017
2
Goldberg-Shprintzen megacolon syndrome with associated sensory motor axonal neuropathy. ( 25846562 )
2015
3
KBP-cytoskeleton interactions underlie developmental anomalies in Goldberg-Shprintzen syndrome. ( 23427148 )
2013
4
KBP interacts with SCG10, linking Goldberg-Shprintzen syndrome to microtubule dynamics and neuronal differentiation. ( 20621975 )
2010
5
KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome. ( 18192286 )
2008
6
Two brothers with Goldberg-Shprintzen syndrome. ( 16760737 )
2006
7
Pachygyria and cerebellar hypoplasia in Goldberg-Shprintzen syndrome. ( 12687674 )
2003
8
A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome). ( 10874640 )
1999
9
Goldberg-Shprintzen syndrome: report of a new family and review of the literature. ( 9571278 )
1998
10
Magnetic resonance imaging abnormalities of the brain in Goldberg-Shprintzen syndrome (Hirschsprung disease, microcephaly, and iris coloboma) ( 9409878 )
1997
11
Hirschsprung disease, unusual face, mental retardation, epilepsy, and congenital heart disease: Goldberg-Shprintzen syndrome. ( 7605558 )
1993
12
Goldberg-Shprintzen syndrome: Hirschsprung disease, hypotonia, and ptosis in sibs. ( 1785632 )
1991

Variations for Goldberg-Shprintzen Syndrome

ClinVar genetic disease variations for Goldberg-Shprintzen Syndrome:

6
(show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 KIF1BP NM_015634.3(KIF1BP): c.78A> G (p.Lys26=) single nucleotide variant Conflicting interpretations of pathogenicity rs144067344 GRCh37 Chromosome 10, 70748666: 70748666
2 KIF1BP NM_015634.3(KIF1BP): c.78A> G (p.Lys26=) single nucleotide variant Conflicting interpretations of pathogenicity rs144067344 GRCh38 Chromosome 10, 68988910: 68988910
3 KIF1BP NM_015634.3(KIF1BP): c.196G> A (p.Gly66Ser) single nucleotide variant Benign rs2255607 GRCh37 Chromosome 10, 70748784: 70748784
4 KIF1BP NM_015634.3(KIF1BP): c.196G> A (p.Gly66Ser) single nucleotide variant Benign rs2255607 GRCh38 Chromosome 10, 68989028: 68989028
5 KIF1BP NM_015634.3(KIF1BP): c.925G> A (p.Glu309Lys) single nucleotide variant Uncertain significance rs76319365 GRCh37 Chromosome 10, 70770706: 70770706
6 KIF1BP NM_015634.3(KIF1BP): c.925G> A (p.Glu309Lys) single nucleotide variant Uncertain significance rs76319365 GRCh38 Chromosome 10, 69010950: 69010950
7 KIF1BP NM_015634.3(KIF1BP): c.1653C> T (p.Ala551=) single nucleotide variant Benign rs35893997 GRCh37 Chromosome 10, 70775959: 70775959
8 KIF1BP NM_015634.3(KIF1BP): c.1653C> T (p.Ala551=) single nucleotide variant Benign rs35893997 GRCh38 Chromosome 10, 69016203: 69016203
9 KIF1BP NM_015634.3(KIF1BP): c.599C> A (p.Ser200Ter) single nucleotide variant Pathogenic rs730882150 GRCh37 Chromosome 10, 70764875: 70764875
10 KIF1BP NM_015634.3(KIF1BP): c.599C> A (p.Ser200Ter) single nucleotide variant Pathogenic rs730882150 GRCh38 Chromosome 10, 69005119: 69005119
11 KIF1BP NM_015634.3(KIF1BP): c.1083dupA (p.Ala362Serfs) duplication Uncertain significance rs886047097 GRCh37 Chromosome 10, 70775389: 70775389
12 KIF1BP NM_015634.3(KIF1BP): c.1083dupA (p.Ala362Serfs) duplication Uncertain significance rs886047097 GRCh38 Chromosome 10, 69015633: 69015633
13 KIF1BP NM_015634.3(KIF1BP): c.976C> T (p.Gln326Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 10, 69011001: 69011001
14 KIF1BP NM_015634.3(KIF1BP): c.976C> T (p.Gln326Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 10, 70770757: 70770757

Expression for Goldberg-Shprintzen Syndrome

Search GEO for disease gene expression data for Goldberg-Shprintzen Syndrome.

Pathways for Goldberg-Shprintzen Syndrome

GO Terms for Goldberg-Shprintzen Syndrome

Cellular components related to Goldberg-Shprintzen Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuronal cell body GO:0043025 9.26 ASCL1 KIF1A RET STMN2
2 axon GO:0030424 8.92 KIF1A NGF RET STMN2

Biological processes related to Goldberg-Shprintzen Syndrome according to GeneCards Suite gene sharing:

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 9.83 ASCL1 EDNRB GDNF NGF RET
2 regulation of gene expression GO:0010468 9.77 ASCL1 EDN3 GDNF
3 neuron projection development GO:0031175 9.74 GDNF STMN1 STMN2
4 nervous system development GO:0007399 9.73 ASCL1 EDNRB GDNF KIF1BP RET STMN1
5 neuron differentiation GO:0030182 9.72 ASCL1 EDN3 RET
6 microtubule-based movement GO:0007018 9.69 KIF18A KIF1A NGF
7 ureteric bud development GO:0001657 9.59 GDNF RET
8 oligodendrocyte development GO:0014003 9.58 ASCL1 MED12
9 regulation of cytoskeleton organization GO:0051493 9.58 STMN1 STMN2
10 response to pain GO:0048265 9.56 EDNRB RET
11 melanocyte differentiation GO:0030318 9.54 EDN3 EDNRB
12 vasoconstriction GO:0042310 9.52 EDN3 EDNRB
13 peripheral nervous system development GO:0007422 9.5 EDNRB GDNF NGF
14 sympathetic nervous system development GO:0048485 9.49 ASCL1 GDNF
15 negative regulation of microtubule polymerization GO:0031115 9.48 STMN1 STMN2
16 regulation of microtubule polymerization or depolymerization GO:0031110 9.46 STMN1 STMN2
17 vein smooth muscle contraction GO:0014826 9.4 EDN3 EDNRB
18 posterior midgut development GO:0007497 9.37 EDNRB RET
19 microtubule depolymerization GO:0007019 9.33 KIF18A STMN1 STMN2
20 enteric nervous system development GO:0048484 9.13 EDNRB GDNF RET
21 neural crest cell migration GO:0001755 8.92 EDN3 EDNRB GDNF RET

Molecular functions related to Goldberg-Shprintzen Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.73 ASCL1 EDNRB GDNF KAT6B KIF18A KIF1A
2 ATP-dependent microtubule motor activity, plus-end-directed GO:0008574 8.62 KIF18A KIF1A

Sources for Goldberg-Shprintzen Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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