Details of Disease

General Information of Disease (ID: DISXYR1H)

• Disease Name: Septooptic dysplasia
• Synonyms: septo-optic dysplasia spectrum; pituitary hormone deficiency, combined, 5; Growth hormone deficiency with pituitary anomalies; septo-optic dysplasia with growth hormone deficiency; hypopituitarism and septooptic 'dysplasia'; septo-optic dysplasia sequence; De Morsier syndrome; septooptic dysplasia; SOD; septo-optic dysplasia
• Definition: Septooptic dysplasia (SOD) is a clinically heterogeneous disorder characterized by the classical triad of optic nerve hypoplasia, pituitary hormone abnormalities and midline brain defects.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISW6YL6: Combined pituitary hormone deficiencies, genetic form
  DISNSX3G: Autosomal genetic disease
  DISXYR1H: Septooptic dysplasia
• Disease Identifiers:
  MONDO ID: MONDO_0008428
  MESH ID: D025962
  UMLS CUI: C0338503
  OMIM ID: 182230
  MedGen ID: 90926
  HPO ID: HP:0100842
  Orphanet ID: 3157
  SNOMED CT ID: 7611002

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
FGFR1	TTRLW2X	Supportive	Autosomal dominant	[1]
PROKR2	TTM67AX	Supportive	Autosomal dominant	[1]
SOX2	TTCNOT6	Supportive	Autosomal dominant	[2]
FGFR1	TTRLW2X	moderate	Genetic Variation	[3]
PROKR2	TTM67AX	moderate	Genetic Variation	[4]
FGF8	TTIUF3J	Strong	Genetic Variation	[1]
GLI2	TT045OH	Strong	Genetic Variation	[5]
SOX2	TTCNOT6	Strong	GermlineCausalMutation	[6]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	Definitive	Genetic Variation	[7]

This Disease Is Related to 14 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ANOS1	OTZJT4KN	Limited	Genetic Variation	[8]
GDF6	OTERXWJU	Limited	Biomarker	[9]
PROK2	OT70IFEZ	Limited	Genetic Variation	[4]
TAX1BP3	OTQ6IB4T	Limited	Genetic Variation	[10]
ARNT2	OTAQD3YV	Supportive	Autosomal dominant	[11]
FGFR1	OT4GLCXW	Supportive	Autosomal dominant	[1]
OTX2	OTTV05B1	Supportive	Autosomal dominant	[12]
PROKR2	OT51C69M	Supportive	Autosomal dominant	[1]
SOX2	OTFAWCAU	Supportive	Autosomal dominant	[2]
SOX3	OT1CRCOB	Supportive	Autosomal dominant	[2]
POU1F1	OTXT8A5C	moderate	Genetic Variation	[7]
CRX	OTH435SV	Strong	Genetic Variation	[13]
HESX1	OT5E2Z4G	Strong	Autosomal recessive	[14]
PROP1	OT8GF6N8	Strong	Genetic Variation	[15]

References

• [1] Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab. 2012 Apr;97(4):E694-9. doi: 10.1210/jc.2011-2938. Epub 2012 Feb 8.
• [2] Genetics of septo-optic dysplasia. Pituitary. 2007;10(4):393-407. doi: 10.1007/s11102-007-0055-5.
• [3] Submicroscopic deletion involving the fibroblast growth factor receptor 1 gene in a patient with combined pituitary hormone deficiency.Endocr J. 2013;60(8):1013-20. doi: 10.1507/endocrj.ej13-0023. Epub 2013 May 9.
• [4] Variations in PROKR2, but not PROK2, are associated with hypopituitarism and septo-optic dysplasia.J Clin Endocrinol Metab. 2013 Mar;98(3):E547-57. doi: 10.1210/jc.2012-3067. Epub 2013 Feb 5.
• [5] Sonic Hedgehog mutations are not a common cause of congenital hypopituitarism in the absence of complex midline cerebral defects.Clin Endocrinol (Oxf). 2015 Apr;82(4):562-9. doi: 10.1111/cen.12565. Epub 2014 Sep 22.
• [6] New insights into septo-optic dysplasia.Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2014;35(1):123-7.
• [7] 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. Clin Endocrinol (Oxf). 2005 Feb;62(2):163-8. doi: 10.1111/j.1365-2265.2004.02189.x.
• [8] Novel application of luciferase assay for the invitro functional assessment of KAL1 variants in three females with septo-optic dysplasia (SOD).Mol Cell Endocrinol. 2015 Dec 5;417:63-72. doi: 10.1016/j.mce.2015.09.010. Epub 2015 Sep 14.
• [9] Improving disease gene prioritization by comparing the semantic similarity of phenotypes in mice with those of human diseases.PLoS One. 2012;7(6):e38937. doi: 10.1371/journal.pone.0038937. Epub 2012 Jun 14.
• [10] Mutations in TAX1BP3 cause dilated cardiomyopathy with septo-optic dysplasia.Hum Mutat. 2015 Apr;36(4):439-42. doi: 10.1002/humu.22759. Epub 2015 Mar 16.
• [11] ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies. Brain. 2013 Oct;136(Pt 10):3096-105. doi: 10.1093/brain/awt218. Epub 2013 Sep 10.
• [12] Septo-optic dysplasia and other midline defects: the role of transcription factors: HESX1 and beyond. Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):115-24. doi: 10.1016/j.beem.2010.06.008.
• [13] Ocular malformations and developmental genes.J AAPOS. 1998 Dec;2(6):317-23. doi: 10.1016/s1091-8531(98)90024-6.
• [14] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [15] Novel Mutations in HESX1 and PROP1 Genes in Combined Pituitary Hormone Deficiency.Horm Res Paediatr. 2015;84(3):153-8. doi: 10.1159/000433468. Epub 2015 Jun 24.