Klinische FragestellungKraniosynostose, Differentialdiagnostik
Zusammenfassung
Umfassendes differentialdiagnostisches panel für Kraniosynostose mit 17 bzw. 69 kuratierten Genen gemäß klinischer Verdachtsdiagnose
152,0 kb (Erweitertes Panel: inkl. additional genes)
- EDTA-Blut (3-5 ml)
NGS +
[Sanger]
Genpanel
Ausgewählte Gene
Name | Exon-Länge (bp) | OMIM-G | Referenz-Seq. | Erbgang |
---|---|---|---|---|
ALX4 | 1236 | NM_021926.4 | AD, AR, Sus | |
EFNB1 | 1041 | NM_004429.5 | XL | |
ERF | 1647 | NM_006494.4 | AD | |
FGFR1 | 2469 | NM_023110.3 | AD | |
FGFR2 | 2466 | NM_000141.5 | AD | |
FGFR3 | 2421 | NM_000142.5 | AD | |
GLI3 | 4743 | NM_000168.6 | AD | |
MSX2 | 804 | NM_002449.5 | AD | |
POR | 2043 | NM_001395413.1 | AR | |
RAB23 | 714 | NM_183227.3 | AR | |
RECQL4 | 3628 | NM_004260.4 | AR | |
SKI | 2187 | NM_003036.4 | AD | |
TCF12 | 2121 | NM_207036.2 | AD | |
TWIST1 | 609 | NM_000474.4 | AD | |
WDR35 | 3546 | NM_001006657.2 | AR | |
ZIC1 | 1344 | NM_003412.4 | AD | |
ALPL | 1575 | NM_000478.6 | AD, AR | |
ARSB | 1602 | NM_000046.5 | AR | |
ASXL1 | 4626 | NM_015338.6 | AD | |
BRAF | 2301 | NM_004333.6 | AD | |
CD96 | 1710 | NM_198196.3 | AD | |
CDC45 | 1819 | NM_001178010.2 | AR | |
COLEC11 | 744 | NM_024027.5 | AR | |
CTSK | 990 | NM_000396.4 | AR | |
CYP26B1 | 1314 | NM_019885.4 | AR | |
FAM20C | 1755 | NM_020223.4 | AR | |
FLNA | 7920 | NM_001456.4 | XL | |
GNPTAB | 3771 | NM_024312.5 | AR | |
HUWE1 | 13125 | NM_031407.7 | XL | |
IDS | 1653 | NM_000202.8 | XLR | |
IDUA | 1962 | NM_000203.5 | AR | |
IFT122 | 3879 | NM_052985.4 | AR | |
IHH | 1236 | NM_002181.4 | AD | |
IL11RA | 1269 | NM_001142784.3 | AR | |
JAG1 | 3657 | NM_000214.3 | AD | |
KAT6A | 6015 | NM_006766.5 | AD | |
KMT2D | 16614 | NM_003482.4 | AD | |
KRAS | 567 | NM_004985.5 | AD | |
MEGF8 | 8337 | NM_001410.3 | AR | |
PHEX | 2250 | NM_000444.6 | XL | |
PTPN11 | 1782 | NM_002834.5 | AD | |
RUNX2 | 1566 | NM_001024630.4 | AD | |
SLC25A24 | 1650 | NM_013386.5 | AD | |
SMAD6 | 1491 | NM_005585.5 | AD | |
SMO | 2364 | NM_005631.5 | AD | |
SOX6 | 2406 | NM_033326.3 | AD | |
SPECC1L | 3354 | NM_015330.6 | AD | |
STAT3 | 2313 | NM_139276.3 | AD | |
TFAP2B | 1383 | NM_003221.4 | AD | |
TGFBR1 | 1512 | NM_004612.4 | AD | |
TGFBR2 | 1704 | NM_003242.6 | AD | |
TLK2 | 2372 | NM_006852.6 | AD | |
TMCO1 | 720 | NM_019026.6 | AR | |
ZEB2 | 3645 | NM_014795.4 | AD |
Infos zur Erkrankung
Die Kraniosynostose ist ein Geburtsfehler des Schädels, der durch den vorzeitigen Verschluss einer oder mehrerer der Faser-Verbindungen zwischen den Schädelnähten gekennzeichnet ist, bevor das Gehirnwachstum abgeschlossen ist. Der Verschluss einer einzelnen Naht kommt häufiger vor. Normalerweise dehnt sich der Schädel gleichmäßig aus, gemäß dem Wachstum des Gehirns. Der vorzeitige Verschluss einer einzelnen Naht schränkt das Wachstum in diesem Bereich des Schädels ein und fördert das Wachstum in anderen Teilen, in denen die Nähte offenbleiben. Dies führt zu einem unförmigen Schädel, verhindert aber nicht, dass sich das Gehirn auf ein normales Volumen ausdehnt. Wenn sich mehrere Nähte vorzeitig schließen, kann sich der Schädel nicht entsprechend ausdehnen, was zum erhöhten Druck im Schädel und gestörter Gehirn-Entwicklung führt. Die Ursache von Kraniosynostosen ist oftmals unbekannt, in der Regel gibt es keine familiäre Vorbelastung. In Fällen, in denen vorzeitig geschlossene Nähte in der Familie vererbt werden, können andere gesundheitliche Probleme wie Krampfanfälle, Blindheit, erhöhter Hirndruck, Mikrozephalie, Hydrozephalus, Entwicklungsverzögerungen oder Beeinträchtigungen der kognitiven Entwicklung auftreten. Zu den genetischen Störungen, die häufig mit Kraniosynostose in Verbindung gebracht werden, gehören eine ganze Reihe verschiedener Syndrome, die mindestens ein Viertel der Fälle ausmachen. Mutationen in einer großen Zahl weiterer Gene verursachen monogene Formen von Kraniosynostosen, wobei alle klassischen Vererbungsmuster bei den syndromalen und isolierten Formen beobachtet werden. Mit entsprechendem klinischem Aufwand können unter den syndromalen Kraniosynostosen in bis >80% der Fälle die genetischen Ursachen anhand umfangreicher DNA-Sequenzanalysen abgeklärt werden. Mutationen in den FGFR2/-3 Genen sind weitaus am häufigsten. Ein negativer molekulargenetischer Befund schließt die klinische Diagnose keinesfalls aus.
Referenz: https://www.ncbi.nlm.nih.gov/books/NBK1455/
- Alias: Fontanelle - craniosynostosis
- Alias: Koronarnaht-Synostose
- Alias: Plagiocephaly, scaphocephaly
- Alias: Premature closure of sutures
- Alias: Synostosis
- Allelic: ACTH-independent macronodular adrenal hyperplasia (GNAS)
- Allelic: Achondroplasia (FGFR3)
- Allelic: Aortic valve disease 2 (SMAD6)
- Allelic: Apert syndrome (FGFR2)
- Allelic: Basal cell carcinoma, somatic (SMO)
- Allelic: Beare-Stevenson cutis gyrata syndrome (FGFR2)
- Allelic: Bent bone dysplasia syndrome (FGFR2)
- Allelic: Bladder cancer, somatic (FGFR3)
- Allelic: Brachydactyly, type A1 (IHH)
- Allelic: CATSHL syndrome (FGFR3)
- Allelic: Cardiac valvular dysplasia, XL (FLNA)
- Allelic: Chitayat syndrome (ERF)
- Allelic: Cleidocranial dysplasia, forme fruste, dental anomalies only (RUNX2)
- Allelic: Colorectal cancer, hereditary nonpolyposis, type 6 (TGFBR2)
- Allelic: Colorectal cancer, somatic (FGFR3)
- Allelic: Congenital short bowel syndrome (FLNA)
- Allelic: Craniofacial-skeletal-dermatologic dysplasia (FGFR2)
- Allelic: Crouzon syndrome (FGFR2)
- Allelic: Crouzon syndrome with acanthosis nigricans (FGFR3)
- Allelic: Curry-Jones syndrome, somatic mosaic (SMO)
- Allelic: Deafness, AD 20/26 (ACTG1)
- Allelic: Deafness, AD 23 (SIX1)
- Allelic: Deafness, congenital heart defects + posterior embryotoxon (JAG1)
- Allelic: Disordered steroidogenesis due to cytochrome P450 oxidoreductase (POR)
- Allelic: Dystonia, juvenile-onset (ACTB)
- Allelic: Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
- Allelic: Esophageal cancer, somatic (TGFBR2)
- Allelic: FG syndrome 2 (FLNA)
- Allelic: Facial clefting, oblique, 1 (SPECC1L)
- Allelic: Gastric cancer, somatic (FGFR2)
- Allelic: Hartsfield syndrome (FGFR1)
- Allelic: Heterotopia, periventricular, 1 (FLNA)
- Allelic: Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
- Allelic: Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
- Allelic: Hypothalamic hamartomas, somatic (GLI3)
- Allelic: Intestinal pseudoobstruction, neuronal (FLNA)
- Allelic: LEOPARD syndrome 3 (BRAF)
- Allelic: Lacrimoauriculodentodigital [LADD] syndrome (FGFR2, FGFR3)
- Allelic: Leukemia, juvenile myelomonocytic, somatic (PTPN11)
- Allelic: Melnick-Needles syndrome (FLNA)
- Allelic: Metachondromatosis (PTPN11)
- Allelic: Metaphyseal dysplasia with maxillary hypoplasia with/-out brachydactyly (RUNX2)
- Allelic: Muenke syndrome (FGFR3)
- Allelic: Myelodysplastic syndrome, somatic (ASXL1)
- Allelic: Naevus, epidermal, somatic (FGFR3)
- Allelic: Odontohypophosphatasia (ALPL)
- Allelic: Osseous heteroplasia, progressive (GNAS)
- Allelic: Osteoglophonic dysplasia (FGFR1)
- Allelic: Otopalatodigital syndrome, type I + II (FLNA)
- Allelic: Parietal foramina 1 (MSX2)
- Allelic: Parietal foramina 2 (ALX4)
- Allelic: Patent ductus arteriosus 2 (TFAP2B)
- Allelic: Pituitary adenoma 3, multiple types, somatic (GNAS)
- Allelic: Polydactyly, postaxial, types A1, B (GLI3)
- Allelic: Polydactyly, preaxial, type IV (GLI3)
- Allelic: Pseudohypoparathyroidism Ia, Ib, Ic (GNAS)
- Allelic: Pseudopseudohypoparathyroidism (GNAS)
- Allelic: RAPADILINO syndrome (RECQL4)
- Allelic: RAS-associated autoimmune leukoproliferative disorder (KRAS)
- Allelic: Radioulnar synostosis, nonsyndromic (SMAD6)
- Allelic: Rothmund-Thomson syndrome, type 2 (RECQL4)
- Allelic: Scaphocephaly, maxillary retrusion, and mental retardation (FGFR2)
- Allelic: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic (KRAS)
- Allelic: Short-rib thoracic dysplasia 7 with/-out polydactyly (WDR35)
- Allelic: Spermatocytic seminoma, somatic (FGFR3)
- Allelic: Sweeney-Cox syndrome (TWIST1)
- Allelic: Terminal osseous dysplasia (FLNA)
- Allelic: Tetralogy of Fallot (JAG1)
- Allelic: Thanatophoric dysplasia, type I, II (FGFR3)
- 3MC syndrome 1 (MASP1)
- 3MC syndrome 2 (COLEC11)
- ACTH-independent macronodular adrenal hyperplasia (GNAS)
- Acrocapitofemoral dysplasia (IHH)
- Alagille syndrome 1 (JAG1)
- Allelic: Developmental and epileptic encephalopathy 91 (PPP3CA)
- Antley-Bixler syndrome with genital anomalies + disordered steroidogenesis (POR)
- Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
- Arboleda-Tham syndrome (KAT6A)
- Arthrogryposis, cleft palate, craniosynostosis,, impaired intellectual development (PPP3CA)
- Au-Kline syndrome (HNRNPK)
- Baller-Gerold syndrome (RECQL4)
- Baraitser-Winter syndrome 1 (ACTB)
- Baraitser-Winter syndrome 2 (ACTG1)
- Basal cell nevus syndrome (PTCH1)
- Bohring-Opitz syndrome (ASXL1)
- Branchiootic syndrome 3 (SIX1)
- C syndrome (CD96)
- CHARGE syndrome (CHD7)
- Cardiac, facial + digital anomalies with developmental delay (TRAF7)
- Cardiofaciocutaneous syndrome (BRAF)
- Cardiofaciocutaneous syndrome 2 (KRAS)
- Carpenter syndrome (RAB23)
- Carpenter syndrome 2 (MEGF8)
- Char syndrome (TFAP2B)
- Cleidocranial dysplasia (RUNX2)
- Cleidocranial dysplasia, forme fruste, with brachydactyly (RUNX2)
- Cole-Carpenter syndrome 1 (P4HB)
- Cranioectodermal dysplasia 1 (IFT122)
- Cranioectodermal dysplasia 2 (WDR35)
- Craniofacial dysmorphism, skeletal anomalies + mental retardation syndrome (TMCO1)
- Craniofrontonasal dysplasia (EFNB1)
- Craniosynostosis + dental anomalies (IL11RA)
- Craniosynostosis 1 (TWIST1)
- Craniosynostosis 2 (MSX2)
- Craniosynostosis 3 (TCF12)
- Craniosynostosis 4 (ERF)
- Craniosynostosis 5, susceptibility to (ALX4)
- Craniosynostosis 6 (ZIC1)
- Craniosynostosis 7, susceptibility to (SMAD6)
- Craniosynostosis with radiohumeral fusions + other skeletal + craniofacial anomalies (CYP26B1)
- Craniosynostosis, nonspecific (FGFR2)
- Craniosynostosis-midfacial hypoplasia-foot abnormalities syndrome (FGFR1, FGFR2)
- Cutis laxa, AR, type IIE (LTBP1)
- Fontaine progeroid syndrome (SLC25A24)
- Frontometaphyseal dysplasia 1 (FLNA)
- Frontonasal dysplasia 2 (ALX4)
- Greig cephalopolysyndactyly syndrome (GLI3)
- Holoprosencephaly 7 (PTCH1)
- Hyper-IgE recurrent infection syndrome (STAT3)
- Hypophosphatasia, adult, childhood, infantile (ALPL)
- Hypophosphatemic rickets, XLD (PHEX)
- Jackson-Weiss syndrome (FGFR1, FGFR2 [FGFR3])
- Kabuki syndrome 1 (KMT2D)
- LEOPARD syndrome 1 (PTPN11)
- Loeys-Dietz syndrome 1 (TGFBR1)
- Loeys-Dietz syndrome 2 (TGFBR2)
- McCune-Albright syndrome, somatic, mosaic (GNAS)
- Meier-Gorlin syndrome 7 (CDC45)
- Mental retardation, AD 57 (TLK2)
- Mental retardation, XL syndromic, Turner type (HUWE1)
- Mowat-Wilson syndrome (ZEB2)
- Mucolipidosis II + III alpha/beta (GNPTAB)
- Mucopolysaccharidosis II (IDS)
- Mucopolysaccharidosis Ih, Ih/s, Is (IDUA)
- Mucopolysaccharidosis type VI [Maroteaux-Lamy] (ARSB)
- Multiple joint dislocations, short stature, craniofacial dysmorph., +/- cong. heart defects (B3GAT3)
- Noonan syndrome 1 (PTPN11)
- Noonan syndrome 3 (KRAS)
- Noonan syndrome 7 (BRAF)
- Oculoectodermal syndrome, somatic (KRAS)
- Opitz GBBB syndrome, type II (SPECC1L)
- Osseous heteroplasia, progressive (GNAS)
- Pallister-Hall syndrome (GLI3)
- Pallister-Hall-like syndrome (SMO)
- Parietal foramina with cleidocranial dysplasia (MSX2)
- Pfeiffer syndome (FGFR1, FGFR2)
- Pseudohypoparathyroidism Ia, Ib, Ic (GNAS)
- Pseudopseudohypoparathyroidism (GNAS)
- Pycnodysostosis (CTSK)
- Raine syndrome (FAM20C)
- Robinow-Sorauf syndrome (TWIST1)
- Saethre-Chotzen syndrome [Acrocephalosyndactyly, type III] (FGFR2)
- Saethre-Chotzen syndrome with or without eyelid anomalies (TWIST1)
- Scaphocephaly and Axenfeld-Rieger anomaly (FGFR2)
- Shprintzen-Goldberg syndrome (SKI)
- Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type (RSPRY1)
- Structural brain anomalies with impaired intellectual development + craniosynostosis (ZIC1)
- Teebi hypertelorism syndrome (SPECC1L)
- Tolchin-Le Caignec syndrome (SOX6)
- Trigonocephaly 1 (FGFR1)
- Weiss-Kruszka syndrome (ZNF462)
- AD
- AR
- Sus
- XL
- XLR
- Multiple OMIM-Ps
Bioinformatik und klinische Interpretation
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