GHDPA
MCID: SPT006
MIFTS: 64

Septooptic Dysplasia (GHDPA)

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

Aliases & Classifications for Septooptic Dysplasia

MalaCards integrated aliases for Septooptic Dysplasia:

Name: Septooptic Dysplasia 56 12 52 25 73 15
Septo-Optic Dysplasia 12 74 52 25 53 58 36 54 43 32
De Morsier Syndrome 56 12 52 25 58 73 54
Growth Hormone Deficiency with Pituitary Anomalies 56 73 29 13 6 71
Sod 12 52 25 58 73
Septo-Optic Dysplasia with Growth Hormone Deficiency 52 73
Pituitary Hormone Deficiency, Combined, 5 56 73
Pituitary Hormone Deficiency, Combined 5 29 6
Septo-Optic Dysplasia Spectrum 52 58
Hypopituitarism and Septooptic 'dysplasia' 52
Dysplasia, Septo-Optic 39
Kallmann Syndrome 71
Ghdpa 73
Cphd5 73

Characteristics:

Orphanet epidemiological data:

58
septo-optic dysplasia spectrum
Inheritance: Autosomal dominant,Autosomal recessive,Multigenic/multifactorial,Not applicable; Prevalence: 1-5/10000 (Europe); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive
autosomal dominant

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


HPO:

31

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Septooptic Dysplasia

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. The first major feature, optic nerve hypoplasia, is the underdevelopment of the optic nerves, which carry visual information from the eyes to the brain. In affected individuals, the optic nerves are abnormally small and make fewer connections than usual between the eyes and the brain. As a result, people with optic nerve hypoplasia have impaired vision in one or both eyes. Optic nerve hypoplasia can also be associated with unusual side-to-side eye movements (nystagmus) and other eye abnormalities. The second characteristic feature of septo-optic dysplasia is the abnormal development of structures separating the right and left halves of the brain. These structures include the corpus callosum, which is a band of tissue that connects the two halves of the brain, and the septum pellucidum, which separates the fluid-filled spaces called ventricles in the brain. In the early stages of brain development, these structures may form abnormally or fail to develop at all. Depending on which structures are affected, abnormal brain development can lead to intellectual disability and other neurological problems. The third major feature of this disorder is pituitary hypoplasia. The pituitary is a gland at the base of the brain that produces several hormones. These hormones help control growth, reproduction, and other critical body functions. Underdevelopment of the pituitary can lead to a shortage (deficiency) of many essential hormones. Most commonly, pituitary hypoplasia causes growth hormone deficiency, which results in slow growth and unusually short stature. Severe cases cause panhypopituitarism, a condition in which the pituitary produces no hormones. Panhypopituitarism is associated with slow growth, low blood sugar (hypoglycemia), genital abnormalities, and problems with sexual development. The signs and symptoms of septo-optic dysplasia can vary significantly. Some researchers suggest that septo-optic dysplasia should actually be considered a group of related conditions rather than a single disorder. About one-third of people diagnosed with septo-optic dysplasia have all three major features; most affected individuals have two of the major features. In rare cases, septo-optic dysplasia is associated with additional signs and symptoms, including recurrent seizures (epilepsy), delayed development, and abnormal movements.

MalaCards based summary : Septooptic Dysplasia, also known as septo-optic dysplasia, is related to pituitary stalk interruption syndrome and schizencephaly. An important gene associated with Septooptic Dysplasia is HESX1 (HESX Homeobox 1), and among its related pathways/superpathways are Mesodermal Commitment Pathway and Signaling pathways regulating pluripotency of stem cells. The drugs Zinc and Menotropins have been mentioned in the context of this disorder. Affiliated tissues include pituitary, brain and eye, and related phenotypes are visual impairment and septo-optic dysplasia

Disease Ontology : 12 A syndrome 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.

NIH Rare Diseases : 52 Septo-optic dysplasia is a disorder of early brain and eye development. The most common features are underdevelopment (hypoplasia) of the eye (optic) nerve , abnormal formation of structures along the midline of the brain such as the absence of the septum pellucidum and the corpus callosum , and a small pituitary (pituitary hypoplasia). Signs and symptoms may include blindness in one or both eyes, an abnormal pupil dilation in response to light, nystagmus (abnormal movement of the eyes), low muscular tone and hormonal problems. Additional features may include recurring seizures , delayed development, intellectual disability , jaundice (yellow-ish skin), precocious puberty, short stature , sleep problems, obesity, lack of smell (anosmia), hearing loss and heart anomalies. Although the cause is unknown in most cases, very few people with SOD may have variations (mutations ) in the HESX1 OTX2 , SOX2 or SOX3 genes . Other factors that may be involved are viral infections, certain medications and a blood flow disruption. Typically, people do not have a family history of septo-optic dysplasia. However, there have been a few cases in which multiple family members have been diagnosed. In these cases inheritance can be autosomal recessive or autosomal dominant . Although there is no cure for this condition, the treatment is directed toward the specific symptoms in each individual. Children with possible SOD must be kept under careful hormonal follow-up, and, if present, hormone deficiencies should be treated with hormone replacement therapy.

OMIM : 56 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)

NINDS : 53 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.

KEGG : 36 Septo-optic dysplasia is a heterogeneous condition with optic nerve hypoplasia, dysgenesis of the septum pellucidum, and pituitary hypofunction.

UniProtKB/Swiss-Prot : 73 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.

Wikipedia : 74 Septo-optic dysplasia (SOD), previously known as de Morsier syndrome, is a rare congenital malformation... more...

Related Diseases for Septooptic Dysplasia

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

(show top 50) (show all 229)
# Related Disease Score Top Affiliating Genes
1 pituitary stalk interruption syndrome 32.6 SOX3 PROKR2 POU1F1 LHX4 HESX1 GHRHR
2 schizencephaly 32.1 SOX2 SIX3 HESX1
3 optic nerve hypoplasia, bilateral 31.6 OTX2 HESX1 ESX1
4 fryns microphthalmia syndrome 31.5 SOX2 OTX2 HESX1
5 hypogonadotropic hypogonadism 31.4 PROP1 PROKR2 HESX1 FGFR1
6 microphthalmia 31.3 SOX2 SIX3 POMC OTX2 HESX1 GLI2
7 growth hormone deficiency 31.2 SOX3 HESX1 GHRHR GH1
8 congenital hypopituitarism 31.0 PROP1 LHX4 HESX1 GLI2
9 lobar holoprosencephaly 31.0 SIX3 GLI2 FGFR1
10 semilobar holoprosencephaly 31.0 SIX3 GLI2 FGFR1
11 hypothalamic disease 31.0 POMC GH1
12 holoprosencephaly 31.0 SOX3 SIX3 PROP1 POU1F1 OTX2 LHX4
13 hypothyroidism, congenital, nongoitrous, 4 31.0 PROP1 POU1F1 POMC GH1
14 empty sella syndrome 31.0 PROP1 POMC LHX3 GH1
15 isolated growth hormone deficiency 30.9 SOX3 PROP1 POU1F1 POMC OTX2 LHX4
16 pituitary hypoplasia 30.9 SOX3 POU1F1 OTX2 LHX4 LHX3 HESX1
17 pituitary adenoma, prolactin-secreting 30.9 POU1F1 POMC GHRHR GH1
18 pituitary adenoma 30.9 POU1F1 POMC GHRHR GH1
19 acth deficiency, isolated 30.8 TBX19 PROP1 POMC LHX4 LHX3
20 cryptorchidism, unilateral or bilateral 30.8 SOX3 PROP1 PROKR2 POMC LHX4 HESX1
21 hypothyroidism 30.8 SOX3 PROP1 POU1F1 POMC LHX4 LHX3
22 kallmann syndrome 30.7 SOX3 SOX2 PROP1 PROKR2 POU1F1 OTX2
23 coloboma of macula 30.5 SOX2 SIX3 PROKR2 OTX2 HESX1 GLI2
24 hypopituitarism 30.4 TBX19 SOX3 SOX2 SIX3 PROP1 PROKR2
25 pituitary gland disease 30.3 TBX19 SOX3 PROP1 POU1F1 POMC LHX4
26 pituitary hormone deficiency, combined, 2 30.1 SOX3 PROP1 PROKR2 POU1F1 POMC OTX2
27 pagon stephan syndrome 11.9
28 central congenital hypothyroidism 11.8
29 craniotelencephalic dysplasia 11.5
30 de morsier's syndrome information 11.5
31 holoprosencephaly 13, x-linked 11.3
32 microphthalmia, syndromic 5 11.3
33 non-acquired panhypopituitarism 10.7 SOX3 PROP1
34 complex chromosomal rearrangement 10.6 SOX3 OTX2
35 central nervous system lipoma 10.6 SIX3 FGFR1
36 melanotic medulloblastoma 10.6 OTX2 GLI2
37 adenohypophysitis 10.6 POMC GH1
38 hypogonadotropic hypogonadism 23 without anosmia 10.6 PROKR2 FGFR1
39 neonatal thyrotoxicosis 10.6 PROP1 LHX3
40 holoprosencephaly, recurrent infections, and monocytosis 10.6 SIX3 GLI2
41 hypothyroidism, central, with testicular enlargement 10.6 PROP1 POU1F1 LHX3
42 chromophobe adenoma 10.6 POMC GH1
43 colobomatous microphthalmia 10.6 SIX3 OTX2 HESX1
44 nodular medulloblastoma 10.6 OTX2 GLI2
45 microphthalmia, isolated 3 10.6 SOX2 OTX2
46 lymphocytic hypophysitis 10.6 TBX19 POMC GH1
47 corpus callosum lipoma 10.6 SIX3 GLI2 FGFR1
48 pituitary tumors 10.6 PROP1 POMC GH1
49 cerebral hemisphere lipoma 10.6 SIX3 GLI2 FGFR1
50 microform holoprosencephaly 10.6 SIX3 GLI2 FGFR1

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



Diseases related to Septooptic Dysplasia

Symptoms & Phenotypes for Septooptic Dysplasia

Human phenotypes related to Septooptic Dysplasia:

58 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 visual impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000505
2 septo-optic dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0100842
3 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
4 hemiplegia/hemiparesis 58 31 frequent (33%) Frequent (79-30%) HP:0004374
5 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
6 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
7 cleft palate 58 31 frequent (33%) Frequent (79-30%) HP:0000175
8 cryptorchidism 58 31 frequent (33%) Frequent (79-30%) HP:0000028
9 hypoplasia of penis 58 31 frequent (33%) Frequent (79-30%) HP:0008736
10 agenesis of corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0001274
11 anterior pituitary hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0010627
12 seizure 31 frequent (33%) HP:0001250
13 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
14 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
15 sleep disturbance 58 31 occasional (7.5%) Occasional (29-5%) HP:0002360
16 sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000407
17 polydipsia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001959
18 fatigue 58 31 occasional (7.5%) Occasional (29-5%) HP:0012378
19 dry skin 58 31 occasional (7.5%) Occasional (29-5%) HP:0000958
20 tracheoesophageal fistula 58 31 occasional (7.5%) Occasional (29-5%) HP:0002575
21 autism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000717
22 hypohidrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000966
23 obesity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001513
24 diabetes insipidus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000873
25 anosmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000458
26 aplasia/hypoplasia of the cerebellum 58 31 occasional (7.5%) Occasional (29-5%) HP:0007360
27 constipation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002019
28 esophageal atresia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002032
29 maternal diabetes 58 31 occasional (7.5%) Occasional (29-5%) HP:0009800
30 abnormality of cardiovascular system morphology 31 occasional (7.5%) HP:0030680
31 absent septum pellucidum 58 31 Frequent (79-30%) HP:0001331
32 optic nerve hypoplasia 58 31 Very frequent (99-80%) HP:0000609
33 seizures 58 Frequent (79-30%)
34 malformation of the heart and great vessels 58 Occasional (29-5%)
35 short finger 31 HP:0009381
36 abnormality of the hypothalamus-pituitary axis 58 Frequent (79-30%)
37 optic disc hypoplasia 31 HP:0007766
38 growth hormone deficiency 31 HP:0000824
39 polydactyly 31 HP:0010442
40 psychomotor retardation 31 HP:0025356

Symptoms via clinical synopsis from OMIM:

56
Endocrine Features:
diabetes insipidus
hypoplasia of anterior pituitary
ectopic or absent posterior pituitary

Head And Neck Eyes:
optic nerve hypoplasia
hypoplastic optic discs

Skeletal Hands:
supernumerary digits
hypoplastic digits

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

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

Growth Height:
short stature (if untreated)

Metabolic Features:
hypoglycemia, neonatal (in some patients)

Clinical features from OMIM:

182230

MGI Mouse Phenotypes related to Septooptic Dysplasia:

45 (show all 15)
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 10.41 ARNT2 FGFR1 GHRHR GLI2 HESX1 LHX3
2 growth/size/body region MP:0005378 10.4 ARNT2 FGFR1 GHRHR GLI2 HESX1 LHX3
3 homeostasis/metabolism MP:0005376 10.33 ARNT2 FGFR1 GHRHR GLI2 LHX3 LHX4
4 nervous system MP:0003631 10.3 ARNT2 FGFR1 GHRHR GLI2 HESX1 LHX3
5 behavior/neurological MP:0005386 10.29 ARNT2 FGFR1 GHRHR GLI2 OTX2 POMC
6 cellular MP:0005384 10.28 ARNT2 FGFR1 GLI2 LHX3 OTX2 POMC
7 mortality/aging MP:0010768 10.28 ARNT2 FGFR1 GLI2 HESX1 LHX3 LHX4
8 craniofacial MP:0005382 10.18 FGFR1 GLI2 HESX1 LHX3 OTX2 POU1F1
9 hearing/vestibular/ear MP:0005377 10.08 FGFR1 GLI2 HESX1 LHX3 OTX2 POU1F1
10 integument MP:0010771 10.03 FGFR1 GHRHR GLI2 POMC PROKR2 SOD1
11 reproductive system MP:0005389 10.03 FGFR1 GHRHR GLI2 LHX3 OTX2 POU1F1
12 pigmentation MP:0001186 9.72 OTX2 POMC POU1F1 SOX2 TBX19
13 respiratory system MP:0005388 9.7 GLI2 HESX1 LHX4 OTX2 PROP1 SIX3
14 skeleton MP:0005390 9.61 FGFR1 GHRHR GLI2 OTX2 POU1F1 SIX3
15 taste/olfaction MP:0005394 8.92 HESX1 OTX2 SIX3 SOX2

Drugs & Therapeutics for Septooptic Dysplasia

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

(show all 41)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Zinc Approved, Investigational Phase 4 7440-66-6 32051
2
Menotropins Approved Phase 4 61489-71-2, 9002-68-0 5360545
3 Chorionic Gonadotropin Phase 4
4 Hypoglycemic Agents Phase 3
5 Pharmaceutical Solutions Phase 3
6
Testosterone Approved, Experimental, Investigational Phase 2 58-22-0, 481-30-1 10204 6013
7 Hormones Phase 2
8 Hormone Antagonists Phase 2
9 Follicle Stimulating Hormone Phase 2
10
Testosterone enanthate Approved Phase 1 315-37-7 9416
11
Testosterone undecanoate Approved, Investigational Phase 1 5949-44-0
12
Methyltestosterone Approved Phase 1 58-18-4 6010
13
Anastrozole Approved, Investigational Phase 1 120511-73-1 2187
14 insulin Phase 1
15 Insulin, Globin Zinc Phase 1
16 Testosterone 17 beta-cypionate Phase 1
17 Androgens Phase 1
18 Estrogens Phase 1
19 Antineoplastic Agents, Hormonal Phase 1
20 Estrogen Antagonists Phase 1
21 Estrogen Receptor Antagonists Phase 1
22 Aromatase Inhibitors Phase 1
23
Ketoconazole Approved, Investigational 65277-42-1 47576
24
Clotrimazole Approved, Vet_approved 23593-75-1 2812
25
Miconazole Approved, Investigational, Vet_approved 22916-47-8 4189
26
Estradiol Approved, Investigational, Vet_approved 50-28-2 5757
27
Estrone Approved 53-16-7 5870
28
Polyestradiol phosphate Approved 28014-46-2
29
Melatonin Approved, Nutraceutical, Vet_approved Early Phase 1 73-31-4 896
30 Acyline Investigational 170157-13-8
31 Antioxidants Early Phase 1
32 Protective Agents Early Phase 1
33 Cytochrome P-450 Enzyme Inhibitors
34 Anti-Infective Agents
35 Antifungal Agents
36 Cytochrome P-450 CYP3A Inhibitors
37 Estradiol 17 beta-cypionate
38 Drospirenone and ethinyl estradiol combination
39 Estradiol 3-benzoate
40 Trisequens
41 Estropipate 7280-37-7

Interventional clinical trials:

(show all 23)
# Name Status NCT ID Phase Drugs
1 Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin is Superior to Human Chorionic Gonadotropin in Therapeutic Efficacy in Adolescent Boys With Congenital Hypogonadotropic Hypogonadism Unknown status NCT02880280 Phase 4 Human Menopausal Gonadotropin;Human Chorionic Gonadotropin
2 Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia Completed NCT00140413 Phase 4 Nutropin AQ
3 Efficacy and Safety of Human Chorionic Gonadotropin (HCG) and Follicle Stimulating Hormone (FSH) in the Treatment of Hypogonadotropic Hypogonadism Completed NCT01403532 Phase 4 Traditional intervention for HH using HCG and FSH;Sequential intervention for HH using HCG and FSH;Sequential intervention for HH using HCG and FSH plus zinc
4 Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in the Treatment of Male Patients With Isolated Hypogonadotropic Hypogonadism: an Open, Randomized Controlled Study Recruiting NCT03687606 Phase 4 Human Chorionic Gonadotropin;human menopausal gonadotropin
5 Confirmatory Validation of Oral Macimorelin as a Growth Hormone (GH) Stimulation Test (ST) for the Diagnosis of Adult Growth Hormone Deficiency (AGHD) in Comparison With the Insulin Tolerance Test (ITT) Completed NCT02558829 Phase 3 Macimorelin;Insulin
6 Pulsatile GnRH in Anovulatory Infertility Recruiting NCT00383656 Phase 2 GnRH
7 Role of FSH in Human Gonadal Development Terminated NCT00064987 Phase 2 gonadotropin releasing hormone (GnRH);follicle stimulating hormone (FSH)
8 Kisspeptin Administration in the Adult Recruiting NCT00914823 Phase 1 kisspeptin 112-121;GnRH
9 Kisspeptin in the Evaluation of Delayed Puberty Recruiting NCT01438034 Phase 1 kisspeptin 112-121;GnRH
10 Effect of Varying Testosterone Levels on Insulin Sensitivity in Men With Idiopathic Hypogonadotropic Hypogonadism Terminated NCT03118479 Phase 1 Anastrozole Pill;Testosterone;Placebo Oral Tablet
11 Identification and Treatment of Biological Clock Dysfunction in Optic Nerve Hypoplasia Unknown status NCT00825591 Early Phase 1
12 Factors Affecting Health Promoting Behavior in Rare Disease Patients: A Mixed Methods Study of Men With Congenital Hypogonadotropic Hypogonadism (CHH) Completed NCT01914172
13 Feedback Control of FSH Secretion in the Human Male Completed NCT00392457 ketoconazole;gonadotropin releasing hormone (GnRH)
14 Effect of Varying Testosterone Levels on Insulin Sensitivity in Normal and IHH Men Completed NCT00470990 GnRH antagonist (Acyline)
15 The Genetic Investigation of Reproductive Disorders (Including Kallmann Syndrome) Recruiting NCT01601171
16 Role of Gonadotropin Pulsations in the Reversal of Hypogonadotropic Hypogonadism Recruiting NCT00392756 gonadotropin releasing hormone (GnRH)
17 Molecular Basis of Inherited Reproductive Disorders Recruiting NCT00494169
18 The Role of Gonadotropin Pulsations in the Regulation of Puberty and Fertility Recruiting NCT01511588
19 The Molecular Basis of Inherited Reproductive Disorders Recruiting NCT01500447
20 Baselines in Reproductive Disorders Recruiting NCT00456274
21 The Effects of 7 Days of Exogenous Pulsatile GnRH Treatment on the Pituitary-Gonadal Axis in Hypogonadotropic Hypogonadal Subjects Active, not recruiting NCT00493961 gonadotropin releasing hormone (GnRH)
22 Kallmann Syndrome in Finland Enrolling by invitation NCT00623116 Short withdrawal of testosterone, gonadotropins or estrogenic compounds (see below)
23 Psychological Outcomes in Isolated GNRH Deficiency Terminated NCT02356172

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:

# Genetic test Affiliating Genes
1 Pituitary Hormone Deficiency, Combined 5 29
2 Growth Hormone Deficiency with Pituitary Anomalies 29

Anatomical Context for Septooptic Dysplasia

MalaCards organs/tissues related to Septooptic Dysplasia:

40
Pituitary, Brain, Eye, Skin, Heart, Thyroid, Testes

Publications for Septooptic Dysplasia

Articles related to Septooptic Dysplasia:

(show top 50) (show all 452)
# Title Authors PMID Year
1
HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism. 56 6 54 61
17148560 2007
2
Sporadic heterozygous frameshift mutation of HESX1 causing pituitary and optic nerve hypoplasia and combined pituitary hormone deficiency in a Japanese patient. 56 6 61 54
12519827 2003
3
Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. 6 56 61 54
11136712 2001
4
Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. 61 54 6 56
9620767 1998
5
A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction. 56 6 61
14561704 2003
6
Evidence for possible Mendelian inheritance of septo-optic dysplasia. 61 6 56
8696006 1996
7
Novel HESX1 mutations associated with a life-threatening neonatal phenotype, pituitary aplasia, but normally located posterior pituitary and no optic nerve abnormalities. 56 6
16940453 2006
8
Enhanced repression by HESX1 as a cause of hypopituitarism and septooptic dysplasia. 61 6 54
14557462 2003
9
Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation. 54 61 56
11891837 2002
10
Septo-optic dysplasia. 61 56
19623216 2010
11
Septo-optic dysplasia with digital anomalies--a recurrent pattern syndrome. 56 61
15368481 2004
12
Septo-optic dysplasia and amniotic bands: further evidence for a vascular pathogenesis. 56 61
14755460 2004
13
Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders. 61 56
11748154 2001
14
Sudden death in septo-optic dysplasia. Report of 5 cases. 56 61
9006427 1997
15
Septo-optic dysplasia in two siblings. 56 61
2346191 1990
16
Hypopituitarism and septooptic "dysplasia" in first cousins. 61 56
4003437 1985
17
Septo-optic dysplasia and median cleft face syndrome in a patient with isolated growth hormone deficiency and hyperprolactinemia. 56 61
6846278 1983
18
Maternal factors in septo-optic dysplasia. 56 61
480051 1979
19
Septo-optic dysplasia (de Morsier syndrome). 56 61
308321 1978
20
Optic nerve hypoplasia with hypopituitarism. Septo-optic dysplasia with hypopituitarism. 61 56
1119454 1975
21
Septo-optic dysplasia with growth hormone deficiency (De Morsier syndrome). 61 56
4647051 1972
22
Septo-optic dysplasia. 56 61
5076259 1972
23
Septo-optic dysplasia and pituitary dwarfism. 61 56
4191531 1970
24
Epidemiology of septo-optic dysplasia with focus on prevalence and maternal age - A EUROCAT study. 52 61
29753093 2018
25
New insights into septo-optic dysplasia. 61 52
24802313 2014
26
Microphthalmia/Anophthalmia/Coloboma Spectrum – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 6
20301552 2004
27
Endocrine status in patients with optic nerve hypoplasia: relationship to midline central nervous system abnormalities and appearance of the hypothalamic-pituitary axis on magnetic resonance imaging. 56
14602762 2003
28
"Hot spot" in the PROP1 gene responsible for combined pituitary hormone deficiency. 6
10323394 1999
29
The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. 6
9745452 1998
30
Median craioencephalic dysraphias and olfactogenital dysplasia. 56
13884418 1962
31
Magnetic resonance diffusion tensor imaging (MRDTI) and tractography in children with septo-optic dysplasia. 54 61
19998031 2010
32
Growth without growth hormone and similar dysmorphic features in three patients with sporadic combined pituitary hormone deficiencies. 61 54
19844116 2009
33
Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism. 61 54
19093031 2008
34
Refining clinical phenotypes in septo-optic dysplasia based on MRI findings. 61 54
18231810 2008
35
Heterozygous mutation of HESX1 causing hypopituitarism and multiple anatomical malformations without features of septo-optic dysplasia. 54 61
18852528 2008
36
A new autosomal recessive syndrome of ocular colobomas, ichthyosis, brain malformations and endocrine abnormalities in an inbred Emirati family. 61 54
18271001 2008
37
[Clinical and genetic aspects of combined pituitary hormone deficiencies]. 61 54
18291347 2008
38
Septo-optic dysplasia associated with abnormal pubertal development. 61 54
17624226 2007
39
Remission of congenital diabetes insipidus after eight years. 54 61
17663299 2007
40
Hypopituitarism oddities: congenital causes. 54 61
18174732 2007
41
Panhypopituitarism: genetic versus acquired etiological factors. 61 54
17315526 2007
42
Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. 54 61
16735499 2006
43
Mutation analysis of POUF-1, PROP-1 and HESX-1 show low frequency of mutations in children with sporadic forms of combined pituitary hormone deficiency and septo-optic dysplasia. 54 61
15670191 2005
44
Prenatal diagnosis of absence of the septum pellucidum associated with septo-optic dysplasia. 61 54
15593257 2005
45
DNA testing in patients with GH deficiency at the time of transition. 61 54
12914740 2003
46
Growth without growth hormone: growth pattern and final height of five patients with idiopathic combined pituitary hormone deficiency. 54 61
12807508 2003
47
Septo-optic dysplasia: a literature review. 61 54
12877274 2003
48
Rest-activity patterns in children with hypopituitarism. 61 54
12777591 2003
49
Isolated GH deficiency (IGHD) type II: imaging of the pituitary gland by magnetic resonance reveals characteristic differences in comparison with severe IGHD of unknown origin. 61 54
12457450 2002
50
Cerebral midline developmental anomalies: endocrine, neuroradiographic and ophthalmological features. 54 61
12503860 2002

Variations for Septooptic Dysplasia

ClinVar genetic disease variations for Septooptic Dysplasia:

6 (show all 29) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HESX1 NM_003865.3(HESX1):c.313T>G (p.Trp105Gly)SNV Pathogenic 492850 rs754137696 3:57232825-57232825 3:57198797-57198797
2 HESX1 NM_003865.3(HESX1):c.240del (p.Glu81fs)deletion Pathogenic 492848 rs777833871 3:57232898-57232898 3:57198870-57198870
3 HESX1 NM_003865.3(HESX1):c.301_302AG[4] (p.Leu103fs)short repeat Pathogenic 7694 3:57232831-57232832 3:57198803-57198804
4 HESX1 NM_003865.3(HESX1):c.77T>C (p.Ile26Thr)SNV Pathogenic 7695 rs28936416 3:57233870-57233870 3:57199842-57199842
5 HESX1 HESX1, 1-BP DEL, 1684Gdeletion Pathogenic 7696
6 HESX1 NM_003865.3(HESX1):c.450_451del (p.Asp150fs)deletion Pathogenic 7697 rs587776664 3:57232427-57232428 3:57198399-57198400
7 HESX1 NM_003865.3(HESX1):c.357+2T>CSNV Pathogenic 7698 rs575112817 3:57232779-57232779 3:57198751-57198751
8 HESX1 NM_003865.3(HESX1):c.445G>A (p.Glu149Lys)SNV Pathogenic 7699 rs104893742 3:57232433-57232433 3:57198405-57198405
9 HESX1 NM_003865.3(HESX1):c.18G>C (p.Gln6His)SNV Pathogenic 7700 rs121909173 3:57233929-57233929 3:57199901-57199901
10 HESX1 NM_003865.3(HESX1):c.478C>T (p.Arg160Cys)SNV Pathogenic 7691 rs28936702 3:57232305-57232305 3:57198277-57198277
11 RALGAPB NM_020336.4(RALGAPB):c.2324G>T (p.Arg775Leu)SNV Likely pathogenic 370037 rs758022116 20:37163795-37163795 20:38535152-38535152
12 HESX1 NM_003865.3(HESX1):c.308T>A (p.Leu103Ter)SNV Likely pathogenic 492849 rs777223697 3:57232830-57232830 3:57198802-57198802
13 HESX1 NM_003865.3(HESX1):c.158-1G>CSNV Likely pathogenic 537760 rs1238248024 3:57232981-57232981 3:57198953-57198953
14 HESX1 NM_003865.3(HESX1):c.183T>C (p.His61=)SNV Conflicting interpretations of pathogenicity 779725 3:57232955-57232955 3:57198927-57198927
15 HESX1 NM_003865.3(HESX1):c.525G>A (p.Ala175=)SNV Conflicting interpretations of pathogenicity 197222 rs141063672 3:57232258-57232258 3:57198230-57198230
16 HESX1 NM_003865.3(HESX1):c.385G>A (p.Val129Ile)SNV Conflicting interpretations of pathogenicity 267733 rs143057250 3:57232493-57232493 3:57198465-57198465
17 HESX1 NM_001376058.1(HESX1):c.-110-166T>GSNV Conflicting interpretations of pathogenicity 346289 rs983243 3:57234222-57234222 3:57200194-57200194
18 HESX1 NM_003865.3(HESX1):c.541A>G (p.Thr181Ala)SNV Uncertain significance 7693 rs28936704 3:57232242-57232242 3:57198214-57198214
19 HESX1 NM_003865.3(HESX1):c.*48G>ASNV Uncertain significance 901509 3:57232177-57232177 3:57198149-57198149
20 HESX1 NM_003865.3(HESX1):c.-6G>ASNV Uncertain significance 902082 3:57233952-57233952 3:57199924-57199924
21 HESX1 NM_003865.3(HESX1):c.*192T>ASNV Uncertain significance 346284 rs886058753 3:57232033-57232033 3:57198005-57198005
22 HESX1 NM_003865.3(HESX1):c.220G>A (p.Val74Met)SNV Uncertain significance 346285 rs148422263 3:57232918-57232918 3:57198890-57198890
23 HESX1 NM_001376058.1(HESX1):c.-110-91_-110-88deldeletion Uncertain significance 346286 rs886058754 3:57234144-57234147 3:57200116-57200119
24 HESX1 NM_001376058.1(HESX1):c.-110-120T>ASNV Uncertain significance 346287 rs549564119 3:57234176-57234176 3:57200148-57200148
25 HESX1 NM_001376058.1(HESX1):c.-110-135deldeletion Uncertain significance 346288 rs886058755 3:57234191-57234191 3:57200163-57200163
26 HESX1 NM_003865.3(HESX1):c.200G>A (p.Ser67Asn)SNV Uncertain significance 492847 rs141863326 3:57232938-57232938 3:57198910-57198910
27 HESX1 NM_003865.3(HESX1):c.460-7A>GSNV Likely benign 801979 3:57232330-57232330 3:57198302-57198302
28 HESX1 NM_003865.3(HESX1):c.90C>T (p.Asp30=)SNV Benign/Likely benign 597755 rs115448575 3:57233857-57233857 3:57199829-57199829
29 HESX1 NM_003865.3(HESX1):c.374A>G (p.Asn125Ser)SNV Benign/Likely benign 282975 rs9878928 3:57232504-57232504 3:57198476-57198476

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

73
# 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

Copy number variations for Septooptic Dysplasia from CNVD:

7
# CNVD ID Chromosome 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

Pathways related to Septooptic Dysplasia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.04 SOX2 OTX2 GLI2 FGFR1
2 11.61 SOX2 HESX1 FGFR1 ESX1
3 10.88 SOX2 SIX3 HESX1 ESX1
4 10.28 SOX2 OTX2 GLI2

GO Terms for Septooptic Dysplasia

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

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.03 TBX19 SOX3 SOX2 SOD1 SIX3 PROP1
2 secretory granule GO:0030141 9.43 SOD1 POMC GHRHR
3 transcription factor complex GO:0005667 9.43 SOX3 SOX2 SIX3 PROP1 LHX3 ARNT2
4 nuclear chromatin GO:0000790 9.4 TBX19 SOX3 SOX2 SIX3 PROP1 POU1F1

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

(show all 22)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 10.09 SOX3 SOX2 SIX3 OTX2 HESX1 GLI2
2 regulation of transcription, DNA-templated GO:0006355 10.03 TBX19 SOX3 SOX2 SIX3 PROP1 POU1F1
3 positive regulation of transcription, DNA-templated GO:0045893 10 SOX2 POU1F1 OTX2 LHX3 GLI2 ARNT2
4 positive regulation of cell proliferation GO:0008284 9.97 POU1F1 GLI2 GHRHR FGFR1 ARNT2
5 negative regulation of transcription by RNA polymerase II GO:0000122 9.97 TBX19 SOX3 SOX2 PROP1 POU1F1 HESX1
6 negative regulation of apoptotic process GO:0043066 9.91 SOD1 PROP1 LHX4 LHX3 GLI2 ARNT2
7 brain development GO:0007420 9.88 SIX3 HESX1 FGFR1 ARNT2
8 lung development GO:0030324 9.77 LHX3 GLI2 FGFR1
9 positive regulation of transcription by RNA polymerase II GO:0045944 9.73 TBX19 SOX3 SOX2 SIX3 PROP1 POU1F1
10 negative regulation of neuron differentiation GO:0045665 9.71 SOX3 SOX2 SIX3
11 placenta development GO:0001890 9.69 SOD1 LHX4 LHX3
12 dorsal/ventral pattern formation GO:0009953 9.67 PROP1 LHX3 GLI2
13 positive regulation of multicellular organism growth GO:0040018 9.63 POU1F1 GHRHR GH1
14 determination of adult lifespan GO:0008340 9.61 POU1F1 GHRHR
15 response to copper ion GO:0046688 9.6 SOD1 MT-CYB
16 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.57 GHRHR GH1
17 regulation of insulin-like growth factor receptor signaling pathway GO:0043567 9.56 POU1F1 GHRHR
18 somatotropin secreting cell differentiation GO:0060126 9.48 PROP1 POU1F1
19 adenohypophysis development GO:0021984 9.46 SOX2 PROP1 POU1F1 GHRHR
20 somatotropin secreting cell development GO:0060133 9.4 POU1F1 GHRHR
21 medial motor column neuron differentiation GO:0021526 9.37 LHX4 LHX3
22 pituitary gland development GO:0021983 9.28 TBX19 SOX3 SOX2 SIX3 PROP1 POU1F1

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

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 10.13 TBX19 SOX3 SOX2 SIX3 PROP1 POU1F1
2 DNA-binding transcription factor activity GO:0003700 9.91 TBX19 SOX2 SIX3 POU1F1 OTX2 GLI2
3 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.91 TBX19 SIX3 PROP1 POU1F1 OTX2 LHX3
4 sequence-specific DNA binding GO:0043565 9.85 SOX2 SIX3 PROP1 POU1F1 OTX2 LHX4
5 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.8 TBX19 LHX4 LHX3 GLI2 ESX1
6 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.65 TBX19 SOX2 SIX3 PROP1 POU1F1 OTX2
7 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.44 TBX19 SOX3 SOX2 SIX3 PROP1 POU1F1

Sources for Septooptic Dysplasia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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