MCID: SPT006
MIFTS: 48

Septooptic Dysplasia

Categories: Genetic diseases, Neuronal diseases, Eye diseases, Endocrine diseases

Aliases & Classifications for Septooptic Dysplasia

MalaCards integrated aliases for Septooptic Dysplasia:

Name: Septooptic Dysplasia 54 12 24 25 71 14
Septo-Optic Dysplasia 12 25 51 29 52 42
De Morsier Syndrome 12 24 25 71 52
Growth Hormone Deficiency with Pituitary Anomalies 54 71 13 69
Sod 12 25 71
Pituitary Hormone Deficiency, Combined, 5 54 71
Septo-Optic Dysplasia with Growth Hormone Deficiency 71
Kallmann Syndrome 69
Cphd5 71
Ghdpa 71

Characteristics:

OMIM:

54
Inheritance:
autosomal dominant
autosomal recessive

Miscellaneous:
variable phenotype
diagnosis made when at least 2/3 features present (optic nerve hypoplasia, hypopituitarism with pituitary hypoplasia, midline forebrain defects)


HPO:

32
septooptic dysplasia:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Septooptic Dysplasia

UniProtKB/Swiss-Prot : 71 Growth hormone deficiency with pituitary anomalies: A disease characterized by low or absent growth hormone levels, in the presence of a hypoplastic anterior pituitary lobe and ectopic or absent posterior pituitary lobe. Pituitary hormone deficiency, combined, 5: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD5 is characterized by complete or partial deficiencies of growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone and adrenocorticotropic hormone. Septooptic dysplasia: A clinically heterogeneous disorder defined by any combination of optic nerve hypoplasia, pituitary gland hypoplasia with panhypopopituitarism, and midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum.

MalaCards based summary : Septooptic Dysplasia, also known as septo-optic dysplasia, is related to hesx1-related combined pituitary hormone deficiency and septo-optic dysplasia spectrum, and has symptoms including short stature, global developmental delay and agenesis of corpus callosum. An important gene associated with Septooptic Dysplasia is HESX1 (HESX Homeobox 1). The drugs Hormone Antagonists and Hormones have been mentioned in the context of this disorder. Affiliated tissues include pituitary, brain and skin, and related phenotypes are endocrine/exocrine gland and growth/size/body region

NINDS : 51 Septo-optic dysplasia (SOD) is a rare disorder characterized by abnormal development of the optic disk, pituitary deficiencies, and often agenesis (absence) of the septum pellucidum (the part of the brain that separates the anterior horns or the lateral ventricles of the brain). Symptoms may include blindness in one or both eyes, pupil dilation in response to light, nystagmus (a rapid, involuntary to-and-fro movement of the eyes), inward and outward deviation of the eyes, hypotonia (low muscle tone), and hormonal problems. Seizures may also occur. In a few cases, jaundice (prolonged yellow skin discoloration) may occur at birth. Intellectual problems vary in severity among individuals. While some children with SOD have normal intelligence, others have learning disabilities. Most, however, are developmentally delayed due to vision impairment or neurological problems.

Genetics Home Reference : 25 Septo-optic dysplasia is a disorder of early brain development. Although its signs and symptoms vary, this condition is traditionally defined by three characteristic features: underdevelopment (hypoplasia) of the optic nerves, abnormal formation of structures along the midline of the brain, and pituitary hypoplasia.

OMIM : 54
Septooptic dysplasia is a clinically heterogeneous disorder loosely defined by any combination of optic nerve hypoplasia, pituitary gland hypoplasia, and midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum (Dattani et al., 1998). The diagnosis of this rare congenital anomaly is made when 2 or more features of the classic triad are present. Approximately 30% of patients have complete manifestations, 62% display hypopituitarism, and 60% have an absent septum pellucidum. The disorder is equally prevalent in males and females and is more common in infants born to younger mothers, with a reported incidence of 1 in 10,000 live births (summary by Webb and Dattani, 2010). Also see 516020.0012 for a form of septooptic dysplasia associated with cardiomyopathy and exercise intolerance. (182230)

Disease Ontology : 12 An autosomal genetic disease characterized by the classical triad of optic nerve hypoplasia, pituitary gland hypoplasia and midline brain defects that has material basis in mutation in the HESX1 gene on chromosome 3p14.

Related Diseases for Septooptic Dysplasia

Diseases related to Septooptic Dysplasia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
id Related Disease Score Top Affiliating Genes
1 hesx1-related combined pituitary hormone deficiency 11.2
2 septo-optic dysplasia spectrum 11.1
3 pituitary stalk interruption syndrome 10.9
4 potter's syndrome 10.3 LHX3 PROP1
5 hypopituitarism 10.1
6 hypothyroidism, congenital, nongoitrous 4 10.1 POU1F1 PROP1
7 kowarski syndrome 10.1 HESX1 POU1F1
8 adamantinous craniopharyngioma 10.0 POU1F1 PROP1
9 headache 9.9
10 arachnoiditis 9.9
11 arachnoid cysts 9.9
12 growth hormone deficiency 9.8
13 cat eye syndrome 9.8
14 epidural spinal canal angiolipoma 9.8 HESX1 LHX3 PROP1
15 rolandic epilepsy, mental retardation, and speech dyspraxia 9.8 HESX1 SOX3
16 schizencephaly 9.8 HESX1 SIX3
17 psychogenic movement 9.7 POU1F1 PROP1
18 grubben de cock borghgraef syndrome 9.5 HESX1 PROP1 SOX3
19 acute myeloid leukemia, susceptibility, gata2-related 9.5 HESX1 LHX3 POU1F1 PROP1
20 uterine ligament clear cell adenocarcinoma 9.5 HESX1 LHX3 POU1F1 PROP1
21 complement receptor deficiency 9.4 HESX1 LHX4 POU1F1 PROP1
22 isolated klippel-feil syndrome 9.1 HESX1 LHX3 LHX4 POU1F1 PROP1
23 corticosterone methyloxidase deficiency 9.0 HESX1 LHX3 LHX4 POU1F1 PROP1
24 pityriasis rotunda 9.0 HESX1 LHX4 POU1F1 SOX3
25 lymphohistiocytoid mesothelioma 8.6 HESX1 LHX3 LHX4 POU1F1 SOX3
26 primary hypomagnesemia 8.2 HESX1 LHX3 LHX4 POU1F1 PROP1 SOX3
27 molybdenum cofactor deficiency b 8.2 HESX1 LHX3 LHX4 POU1F1 PROP1 SOX3
28 mental retardation, x-linked syndromic, christianson type 8.2 HESX1 LHX3 LHX4 POU1F1 PROP1 SOX3
29 allergic asthma 8.2 HESX1 LHX3 LHX4 POU1F1 PROP1 SOX3
30 aminoacylase 1 deficiency 7.1 HESX1 LHX3 LHX4 POU1F1 PROP1 SIX3

Graphical network of the top 20 diseases related to Septooptic Dysplasia:



Diseases related to Septooptic Dysplasia

Symptoms & Phenotypes for Septooptic Dysplasia

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
psychomotor retardation
absent septum pellucidum
absent corpus callosum
midline forebrain defects

Head And Neck- Eyes:
optic nerve hypoplasia
hypoplastic optic discs

Growth- Height:
short stature (if untreated)

Metabolic Features:
hypoglycemia, neonatal (in some patients)

Laboratory- Abnormalities:
low or absent growth hormone (gh)
low or absent luteinizing hormone (lh)
low or absent adrenocorticotropic hormone (acth)
low or absent thyrotropin (tsh)
low or absent follicle-stimulating hormone (fsh)

Endocrine Features:
diabetes insipidus
hypoplasia of anterior pituitary
ectopic or absent posterior pituitary

Skeletal- Hands:
supernumerary digits
hypoplastic digits


Clinical features from OMIM:

182230

Human phenotypes related to Septooptic Dysplasia:

32 (show all 11)
id Description HPO Frequency HPO Source Accession
1 short stature 32 HP:0004322
2 global developmental delay 32 HP:0001263
3 agenesis of corpus callosum 32 HP:0001274
4 optic nerve hypoplasia 32 HP:0000609
5 growth hormone deficiency 32 HP:0000824
6 diabetes insipidus 32 HP:0000873
7 anterior pituitary hypoplasia 32 HP:0010627
8 polydactyly 32 HP:0010442
9 absent septum pellucidum 32 HP:0001331
10 optic disc hypoplasia 32 HP:0007766
11 short finger 32 HP:0009381

UMLS symptoms related to Septooptic Dysplasia:


anosmia

MGI Mouse Phenotypes related to Septooptic Dysplasia:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.91 HESX1 LHX3 LHX4 POU1F1 PROP1 SOD1
2 growth/size/body region MP:0005378 9.87 HESX1 LHX3 POU1F1 PROP1 SIX3 SOD1
3 craniofacial MP:0005382 9.8 HESX1 LHX3 POU1F1 SIX3 SOX3
4 mortality/aging MP:0010768 9.76 HESX1 LHX3 LHX4 POU1F1 PROP1 SIX3
5 hearing/vestibular/ear MP:0005377 9.56 LHX3 POU1F1 SOD1 HESX1
6 nervous system MP:0003631 9.56 HESX1 LHX3 LHX4 POU1F1 PROP1 SIX3
7 reproductive system MP:0005389 9.02 LHX3 POU1F1 PROP1 SOD1 SOX3

Drugs & Therapeutics for Septooptic Dysplasia

Drugs for Septooptic Dysplasia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Hormone Antagonists Phase 4,Phase 3
2 Hormones Phase 4,Phase 3
3 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4,Phase 3
4
Zinc Approved Phase 3 7440-66-6 32051 23994
5 Hypoglycemic Agents Phase 3
6 insulin Phase 3
7 Insulin, Globin Zinc Phase 3
8 Pharmaceutical Solutions Phase 3
9
Melatonin Approved, Nutraceutical, Vet_approved Early Phase 1 73-31-4 896
10 Antioxidants Early Phase 1
11 Central Nervous System Depressants Early Phase 1
12 Protective Agents Early Phase 1

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia Completed NCT00140413 Phase 4 Nutropin AQ
2 Validation of Macimorelin as a Test for Adult Growth Hormone Deficiency Completed NCT02558829 Phase 3 Macimorelin;Insulin
3 Biological Clock Dysfunction in Optic Nerve Hypoplasia Unknown status NCT00825591 Early Phase 1

Search NIH Clinical Center for Septooptic Dysplasia

Cochrane evidence based reviews: septo-optic dysplasia

Genetic Tests for Septooptic Dysplasia

Genetic tests related to Septooptic Dysplasia:

id Genetic test Affiliating Genes
1 Septo-Optic Dysplasia 29
2 Septooptic Dysplasia 24 HESX1

Anatomical Context for Septooptic Dysplasia

MalaCards organs/tissues related to Septooptic Dysplasia:

39
Pituitary, Brain, Skin, Thyroid, Eye, Testes

Publications for Septooptic Dysplasia

Articles related to Septooptic Dysplasia:

id Title Authors Year
1
Increased Intraocular Pressure in a Patient With Septooptic Dysplasia: A Case Report. ( 27136085 )
2016
2
Septooptic Dysplasia with an Associated Arachnoid Cyst. ( 27891281 )
2016
3
Incidental discovery of subtle-variant septooptic dysplasia in an adult with headaches: a novel case with pathophysiologic implications. ( 23333409 )
2013
4
HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism. ( 17148560 )
2007
5
Enhanced repression by HESX1 as a cause of hypopituitarism and septooptic dysplasia. ( 14557462 )
2003
6
Septooptic dysplasia. ( 12733175 )
2002
7
Septooptic dysplasia (de Morsier syndrome). ( 3999191 )
1985

Variations for Septooptic Dysplasia

UniProtKB/Swiss-Prot genetic disease variations for Septooptic Dysplasia:

71
id Symbol AA change Variation ID SNP ID
1 HESX1 p.Arg160Cys VAR_010225 rs28936702
2 HESX1 p.Gln6His VAR_063230 rs121909173
3 HESX1 p.Ile26Thr VAR_063231 rs28936416
4 HESX1 p.Glu149Lys VAR_063232 rs104893742
5 HESX1 p.Ser170Leu VAR_063233 rs28936703
6 HESX1 p.Thr181Ala VAR_063234 rs28936704

ClinVar genetic disease variations for Septooptic Dysplasia:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 HESX1 NM_003865.2(HESX1): c.478C> T (p.Arg160Cys) single nucleotide variant Pathogenic rs28936702 GRCh37 Chromosome 3, 57232305: 57232305
2 HESX1 NM_003865.2(HESX1): c.541A> G (p.Thr181Ala) single nucleotide variant Pathogenic rs28936704 GRCh37 Chromosome 3, 57232242: 57232242
3 HESX1 HESX1, 2-BP INS, 306AG insertion Pathogenic
4 HESX1 NM_003865.2(HESX1): c.77T> C (p.Ile26Thr) single nucleotide variant Pathogenic rs28936416 GRCh37 Chromosome 3, 57233870: 57233870
5 HESX1 HESX1, 1-BP DEL, 1684G deletion Pathogenic
6 HESX1 NM_003865.2(HESX1): c.450_451delCA (p.Asp150Glufs) deletion Pathogenic rs587776664 GRCh37 Chromosome 3, 57232427: 57232428
7 HESX1 NM_003865.2(HESX1): c.357+2T> C single nucleotide variant Pathogenic rs575112817 GRCh37 Chromosome 3, 57232779: 57232779
8 HESX1 NM_003865.2(HESX1): c.445G> A (p.Glu149Lys) single nucleotide variant Pathogenic rs104893742 GRCh37 Chromosome 3, 57232433: 57232433
9 HESX1 NM_003865.2(HESX1): c.18G> C (p.Gln6His) single nucleotide variant Pathogenic rs121909173 GRCh37 Chromosome 3, 57233929: 57233929
10 HESX1 NM_003865.2(HESX1): c.511_512delCA (p.Gln171Valfs) deletion Pathogenic rs752434998 GRCh37 Chromosome 3, 57232271: 57232272

Copy number variations for Septooptic Dysplasia from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 176835 3 51400000 54400000 Copy number HESX1 Septo-optic dysplasia

Expression for Septooptic Dysplasia

Search GEO for disease gene expression data for Septooptic Dysplasia.

Pathways for Septooptic Dysplasia

GO Terms for Septooptic Dysplasia

Cellular components related to Septooptic Dysplasia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.23 HESX1 LHX3 LHX4 POU1F1 PROP1 SIX3
2 transcription factor complex GO:0005667 9.13 LHX3 POU1F1 PROP1

Biological processes related to Septooptic Dysplasia according to GeneCards Suite gene sharing:

(show all 15)
id Name GO ID Score Top Affiliating Genes
1 transcription, DNA-templated GO:0006351 9.99 HESX1 LHX3 LHX4 POU1F1 SIX3 SOX3
2 regulation of transcription, DNA-templated GO:0006355 9.91 HESX1 LHX3 LHX4 POU1F1 PROP1 SIX3
3 negative regulation of transcription from RNA polymerase II promoter GO:0000122 9.83 HESX1 POU1F1 PROP1 SOX3
4 negative regulation of apoptotic process GO:0043066 9.78 LHX3 LHX4 PROP1 SOD1
5 positive regulation of transcription from RNA polymerase II promoter GO:0045944 9.76 LHX3 POU1F1 PROP1 SIX3
6 animal organ morphogenesis GO:0009887 9.61 LHX3 LHX4 PROP1
7 transcription from RNA polymerase II promoter GO:0006366 9.56 LHX3 POU1F1 PROP1 SIX3
8 negative regulation of neuron differentiation GO:0045665 9.55 SIX3 SOX3
9 dorsal/ventral pattern formation GO:0009953 9.54 LHX3 PROP1
10 motor neuron axon guidance GO:0008045 9.49 LHX3 LHX4
11 adenohypophysis development GO:0021984 9.4 POU1F1 PROP1
12 placenta development GO:0001890 9.33 LHX3 LHX4 SOD1
13 somatotropin secreting cell differentiation GO:0060126 9.32 POU1F1 PROP1
14 pituitary gland development GO:0021983 9.02 HESX1 LHX3 POU1F1 SIX3 SOX3
15 medial motor column neuron differentiation GO:0021526 8.96 LHX3 LHX4

Molecular functions related to Septooptic Dysplasia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 chromatin binding GO:0003682 9.58 HESX1 POU1F1 PROP1
2 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000978 9.5 HESX1 LHX3 POU1F1
3 DNA binding GO:0003677 9.5 HESX1 LHX3 LHX4 POU1F1 PROP1 SIX3
4 RNA polymerase II distal enhancer sequence-specific DNA binding GO:0000980 9.37 PROP1 SIX3
5 RNA polymerase II transcription factor binding GO:0001085 9.26 LHX3 POU1F1
6 transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding GO:0001205 9.16 PROP1 SIX3
7 sequence-specific DNA binding GO:0043565 9.1 HESX1 LHX3 LHX4 POU1F1 PROP1 SIX3

Sources for Septooptic Dysplasia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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