IllnessCraniosynostosis, differential diagnostics

NGS +

[Sanger]

Craniosynostosis is a birth defect of the skull characterized by premature closure of one or more of the fibrous connections between the cranial sutures before brain growth is complete. Closure of a single suture is more common. Normally, the skull expands uniformly, according to the growth of the brain; premature closure of a single suture restricts growth in that area of the skull and promotes growth in other parts where the sutures remain open. This results in a misshapen skull, but does not prevent the brain from expanding to a normal volume. When multiple sutures close prematurely, the skull cannot expand appropriately, resulting in increased pressure in the skull and disturbed brain development. The cause of craniosynostosis is often unknown, and there is usually no family history of the condition. In cases where prematurely closed sutures are inherited in the family, other health problems such as seizures, blindness, increased intracranial pressure, microcephaly, hydrocephalus, developmental delays or impaired cognitive development may occur. Genetic disorders commonly associated with craniosynostosis include a wide range of different syndromes that account for at least a quarter of cases. Mutations in a large number of other genes cause monogenic forms of craniosynostosis, and all the classic inheritance patterns are observed in syndromic and non-syndromic cases. With appropriate clinical effort, among syndromal craniosynostoses, genetic causes can be clarified in up to >80 of cases using extensive DNA sequence analysis. Mutations in the FGFR2/-3 genes are by far the most common. A negative molecular genetic finding by no means excludes the clinical diagnosis.

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)