IllnessCraniosynostosis, frequently mutated genes; differential diagnosis

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: Achondroplasia (FGFR3)
• Allelic: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
• Allelic: Aortic valve disease 2 (SMAD6)
• Allelic: Apert syndrome (FGFR2)
• Allelic: Beare-Stevenson cutis gyrata syndrome (FGFR2)
• Allelic: Bent bone dysplasia syndrome (FGFR2)
• Allelic: Bladder cancer, somatic (FGFR3)
• Allelic: CATSHL syndrome (FGFR3)
• Allelic: Chitayat syndrome (ERF)
• Allelic: Colorectal cancer, somatic (FGFR3)
• Allelic: Craniofacial-skeletal-dermatologic dysplasia (FGFR2)
• Allelic: Crouzon syndrome (FGFR2)
• Allelic: Crouzon syndrome with acanthosis nigricans (FGFR3)
• Allelic: Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
• Allelic: Gastric cancer, somatic (FGFR2)
• Allelic: Hartsfield syndrome (FGFR1)
• Allelic: Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Allelic: Lacrimoauriculodentodigital [LADD] syndrome (FGFR2, FGFR3)
• Allelic: Muenke syndrome (FGFR3)
• Allelic: Naevus, epidermal, somatic (FGFR3)
• Allelic: Osteoglophonic dysplasia (FGFR1)
• Allelic: Radioulnar synostosis, nonsyndromic (SMAD6)
• Allelic: Scaphocephaly, maxillary retrusion, and mental retardation (FGFR2)
• Allelic: Spermatocytic seminoma, somatic (FGFR3)
• Allelic: Sweeney-Cox syndrome (TWIST1)
• Allelic: Thanatophoric dysplasia, type I, II (FGFR3)
• Craniofrontonasal dysplasia (EFNB1)
• Craniosynostosis 1 (TWIST1)
• Craniosynostosis 3 (TCF12)
• Craniosynostosis 4 (ERF)
• Craniosynostosis 7, susceptibility to (SMAD6)
• Craniosynostosis, nonspecific (FGFR2)
• Craniosynostosis-midfacial hypoplasia-foot abnormalities syndrome (FGFR1, FGFR2)
• Jackson-Weiss syndrome (FGFR1, FGFR2 [FGFR3])
• Pfeiffer syndome (FGFR1, FGFR2)
• Robinow-Sorauf syndrome (TWIST1)
• Saethre-Chotzen syndrome [Acrocephalosyndactyly, type III] (FGFR2)
• Scaphocephaly and Axenfeld-Rieger anomaly (FGFR2)