Klinische FragestellungHypophysenhormon-Defizienz, Differentialdiagnose

NGS +

[Sanger]

Der Hypophysenvorderlappen produziert und sezerniert spezifische Hormone wie Wachstumshormon (GH), Prolactin (PRL), Thyroidea-stimulierendes Hormon (TSH), Luteinisierendes Hormon (LH), Follikel-stimulierendes Hormon (FSH) und Adrenocorticotropische Hormon (ACTH). Insbesondere früh wirkende Faktoren, die sich an der Hypophysen-Organogenese beteiligen, sind nicht Hypophysen-spezifisch, sondern werden auch für die Entwicklung anderer Organe und Strukturen benötigt. Läsionen in diesen Genen können auch Defekte in der Entwicklung von kraniofazialen, sensorischen oder vielen anderen Strukturen verursachen. Stattdessen sind Faktoren, die später in der Spezifikation der hypophysären Zelllinien wirken, eher spezifisch für jeden Zelltyp, aber nicht unbedingt auf die sich entwickelnde oder reife Hypophyse beschränkt. Eine gestörte Expression oder Funktion dieser Faktoren verursacht Störungen in der Hypophyse und führt schließlich zur defizienten Sekretion von Hypophysen-Hormonen. Daher umfasst dieses panel viele Gene, deren Malfunktion zu einer sehr breiten klinischen Symptompalette führen kann. Es werden alle monogenen und auch multifaktorielle Erbgänge beobachtet. In 20–30% der familiären Fälle werden vollständig penetrante Mutationen in bekannten Genen identifiziert. Die DNA-diagnostische Ausbeute ist jedoch derzeit insgesamt nicht bekannt, sodass eine klinische Diagnose durch ein negatives molekulargenetisches Ergebnis keinesfalls ausgeschlossen werden kann.

Referenzen: https://www.ncbi.nlm.nih.gov/books/NBK1347/

https://www.ncbi.nlm.nih.gov/books/NBK97965https://www.ncbi.nlm.nih.gov/books/NBK1334//

https://www.ncbi.nlm.nih.gov/books/NBK476671/

• Allelic: Mitochondrial complex II deficiency, nuclear type 1 (SDHA)
• Alias: Combined pituitary hormone deficiency, included
• Alias: Congenital combined pituitary hormone deficiency, included
• Alias: Congenital hypopituitarism, included
• Alleic: Atrial fibrillation, familial, 3 (KCNQ1)
• Alleic: Long QT syndrome 1 (KCNQ1)
• Allelic. Cardiomyopathy, dilated, 1GG (SDHA)
• Allelic. Mitochondrial complex II deficiency, nuclear type 4 (SDHB)
• Allelic: Agammaglobulinemia, X-linked 1 (BTK)
• Allelic: Anterior segment dysgenesis 4 (PITX2)
• Allelic: Axenfeld-Rieger syndrome, type 1 (PITX2)
• Allelic: Basal cell carcinoma, somatic (PTCH1)
• Allelic: Basal cell nevus syndrome (PTCH1)
• Allelic: Carcinoid tumor of lung (MEN1)
• Allelic: Colorectal cancer, hereditary nonpolyposis, type 1 (MSH2)
• Allelic: Colorectal cancer, hereditary nonpolyposis, type 2 (MLH1)
• Allelic: Colorectal cancer, hereditary nonpolyposis, type 4 (PMS2)
• Allelic: Colorectal cancer, hereditary nonpolyposis, type 5 (MSH6)
• Allelic: Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
• Allelic: Endometrial cancer, familial (MSH6)
• Allelic: Gastrointestinal stromal tumor (SDHB, SDHC)
• Allelic: Greig cephalopolysyndactyly syndrome (GLI3)
• Allelic: Hartsfield syndrome (FGFR1)
• Allelic: Hirschsprung disease, protection against (RET)
• Allelic: Hirschsprung disease, susceptibility to, 1 (RET)
• Allelic: Holoprosencephaly 3 (SHH)
• Allelic: Holoprosencephaly 9 (GLI2)
• Allelic: Hypercholesterolemia, familial, modifier of (GHR)
• Allelic: Increased responsiveness to growth hormone (GHR)
• Allelic: Jackson-Weiss syndrome (FGFR1)
• Allelic: Kowarski syndrome (GH1)
• Allelic: Laron dwarfism (GHR)
• Allelic: Long QT syndrome 1, acquired, susceptibility to (KCNQ1)
• Allelic: Medullary thyroid carcinoma (RET)
• Allelic: Mental retardation, XL, with isolated growth hormone deficiency (SOX3)
• Allelic: Microphthalmia with coloboma 5 (SHH)
• Allelic: Microphthalmia, syndromic 3 (SOX2)
• Allelic: Microphthalmia, syndromic 5 (OTX2)
• Allelic: Mitochondrial complex II deficiency, nuclear type 3 (SDHD)
• Allelic: Muir-Torre syndrome (MLH1, MSH2)
• Allelic: Myxoma, intracardiac (PRKAR1A)
• Allelic: Neurodegeneration with ataxia + late-onset optic atrophy (SDHA)
• Allelic: Optic nerve hypoplasia + abnormalities of the central nervous system (SOX2)
• Allelic: Osteoglophonic dysplasia (FGFR1)
• Allelic: PCWH syndrome (SOX10)
• Allelic: Pfeiffer syndrome (FGFR1)
• Allelic: Pleuropulmonary blastoma (DICER1)
• Allelic: Polydactyly, postaxial, types A1 + B (GLI3)
• Allelic: Polydactyly, preaxial, type IV (GLI3)
• Allelic: Precocious puberty, central, 1 (KISS1R)
• Allelic: Retinal dystrophy, early-onset, with/-out pituitary dysfunction (OTX2)
• Allelic: Rhabdomyosarcoma, embryonal, 2 (DICER1)
• Allelic: Ring dermoid of cornea (PITX2)
• Allelic: Schizencephaly (SHH, SIX3)
• Allelic: Septooptic dysplasia (HESX1)
• Allelic: Short QT syndrome 2 (KCNQ1)
• Allelic: Single median maxillary central incisor (SHH)
• Allelic: Spastic paraplegia 39, AR (PNPLA6)
• Allelic: Trigonocephaly (FGFR1)
• Allelic: Waardenburg syndrome, type 4C (SOX10)
• ACTH-independent macronodular adrenal hyperplasia (GNAS)
• Acrodysostosis 1, with/-out hormone resistance (PRKAR1A)
• Adrenocorticotropic hormone deficiency (TBX19)
• Alopecia, neurologic defects + endocrinopathy syndrome (RBM28)
• Boucher-Neuhauser syndrome (PNPLA6)
• Brain, CNS + PNS cancer [panelapp] (MLH1, MSH2, MSH6)
• CHARGE syndrome (CHD7)
• CHARGE syndrome (SEMA3E)
• Cardioacrofacial dysplasia 2 (PRKACB)
• Carney complex, type 1 (PRKAR1A)
• Charcot-Marie-Tooth disease, demyelinating, type 1I (POLR3B)
• Congenital complex pituitary hormone deficiency (FOXA2)
• Cornelia de Lange syndrome 2 (SMC1A)
• Culler-Jones syndrome (GLI2)
• Developmental + epileptic encephalopathy 85, with/-out midline brain defects (SMC1A)
• Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
• Goiter, multinodular 1, with/-out Sertoli-Leydig cell tumors (DICER1)
• Growth hormone deficiency with pituitary anomalies (HESX1)
• Growth hormone deficiency, isolated partial (GHSR)
• Growth hormone deficiency, isolated, type IA, IB, II (GH1)
• Growth hormone deficiency, isolated, type IV (GHRHR)
• Growth hormone insensitivity, partial (GHR)
• Heterotaxy, visceral, 5 (NODAL)
• Holoprosencephaly (DISP1)
• Holoprosencephaly 11 (CDON)
• Holoprosencephaly 13, XL (STAG2)
• Holoprosencephaly 2 (SIX3)
• Holoprosencephaly 3 (SHH)
• Holoprosencephaly 4 (TGIF1)
• Holoprosencephaly 5 (ZIC2)
• Holoprosencephaly 7 (PTCH1)
• Holoprosencephaly [A-/Lobar, Microform, Midline interhemispheric v., Semilobar, Septooptic] (FOXH1)
• Holoprosencephaly [A-/Lobar, Microform, Midline interhemispheric var., Semilobar, Septooptic] (GAS1)
• Hypogonadotropic hypogonadism 1 with/-out anosmia, Kallmann syndrome 1 (ANOS1)
• Hypogonadotropic hypogonadism 10 with-out anosmia (TAC3)
• Hypogonadotropic hypogonadism 11 with/-out anosmia (TACR3)
• Hypogonadotropic hypogonadism 12 with/-out anosmia (GNRH1)
• Hypogonadotropic hypogonadism 13 with/-out anosmia (KISS1)
• Hypogonadotropic hypogonadism 14 with/-out anosmia (WDR11)
• Hypogonadotropic hypogonadism 15 with/-out anosmia (HS6ST1)
• Hypogonadotropic hypogonadism 16 with/-out anosmia (SEMA3A)
• Hypogonadotropic hypogonadism 17 with/-out anosmia (SPRY4)
• Hypogonadotropic hypogonadism 18 with/-out anosmia (IL17RD)
• Hypogonadotropic hypogonadism 19 with/-out anosmia (DUSP6)
• Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Hypogonadotropic hypogonadism 20 with/-out anosmia (FGF17)
• Hypogonadotropic hypogonadism 21 with anosmia (FLRT3)
• Hypogonadotropic hypogonadism 22, with/-out anosmia (FEZF1)
• Hypogonadotropic hypogonadism 3 with/-out anosmia (PROKR2)
• Hypogonadotropic hypogonadism 4 with/-out anosmia (PROK2)
• Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
• Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
• Hypogonadotropic hypogonadism 7 without anosmia (GNRHR)
• Hypogonadotropic hypogonadism 8 with/-out anosmia (KISS1R)
• Hypogonadotropic hypogonadism 9 with/-out anosmia (NSMF)
• Hypogonadotropic hypogonadism [Lit.] (AXL)
• Hypogonadotropic hypogonadism [panelapp] (IGSF10)
• Hypothyroidism, central + testicular enlargement (IGSF1)
• Immunodeficiency, common variable, 10 (NFKB2)
• Isolated GnRH hormone deficiency (CCDC14)
• Isolated gonadotropin-releasing hormone deficiency [] genereview (SRA1)
• Isolated growth hormone deficiency, type III, with agammaglobulinemia (BTK)
• Jervell and Lange-Nielsen syndrome (KCNQ1)
• Johanson-Blizzard syndrome (UBR1)
• Laurence-Moon syndrome (PNPLA6)
• Leukodystrophy, hypomyelinating, 8, with/-out oligodontia +/- hypogonadotropic hypogonadism (POLR3B)
• McCune-Albright syndrome, somatic, mosaic (GNAS)
• Mismatch repair cancer syndrome 1 (MLH1)
• Mismatch repair cancer syndrome 2 (MSH2)
• Mismatch repair cancer syndrome 3 (MSH6)
• Mismatch repair cancer syndrome 4 (PMS2)
• Mullegama-Klein-Martinez syndrome (STAG2)
• Multiple endocrine neoplasia 1 (MEN1)
• Multiple endocrine neoplasia 1 [panelapp] (CDKN1A)
• Multiple endocrine neoplasia 1 [panelapp] (CDKN2B)
• Multiple endocrine neoplasia 1 [panelapp] (CDKN2C)
• Multiple endocrine neoplasia IIA + IIB (RET)
• Neurodevelopmental disorder with nonspecific brain abnormalities, with/-out seizures (DLL1)
• Oliver-McFarlane syndrome (PNPLA6)
• Optic nerve hypoplasia and abnormalities of the CNS (SOX2)
• Osseous heteroplasia, progressive (GNAS)
• Pallister-Hall syndrome (GLI3)
• Panhypopituitarism, XL (SOX3)
• Paraganglioma + gastric stromal sarcoma (SDHB, SDHC, SDHD)
• Paragangliomas 1, with/-out deafness (SDHD)
• Paragangliomas 3 (SDHC)
• Paragangliomas 4 (SDHB)
• Paragangliomas 5 (SDHA)
• Pheochromocytoma (RET, SDHB, SDHD)
• Pheochromocytoma, susceptibility to (MAX)
• Pigmented nodular adrenocortical disease, primary, 1 (PRKAR1A)
• Pituitary adenoma 1, multiple types (AIP)
• Pituitary adenoma 2, GH-secreting (GPR101)
• Pituitary adenoma 3, multiple types, somatic (GNAS)
• Pituitary adenoma 4, ACTH-secreting, somatic (USP8)
• Pituitary adenoma predisposition (AIP)
• Pituitary hormone deficiency (KCNQ1)
• Pituitary hormone deficiency (TCF7L1)
• Pituitary hormone deficiency, combined, 1 (POU1F1)
• Pituitary hormone deficiency, combined, 2 (PROP1)
• Pituitary hormone deficiency, combined, 3 (LHX3)
• Pituitary hormone deficiency, combined, 4 (LHX4)
• Pituitary hormone deficiency, combined, 5 (HESX1)
• Pituitary hormone deficiency, combined, 6 (OTX2)
• Pseudohypoparathyroidism Ia, Ib, Ic (GNAS)
• Pseudopseudohypoparathyroidism (GNAS)
• Retinal dystrophy, early-onset, with/-out pituitary dysfunction (OTX2)
• Waardenburg syndrome, type 2E, with/-out neurologic involvement (SOX10)
• Webb-Dattani syndrome (ARNT2)