IllnessFGFR-craniosynostosis syndrome, differential diagnosis

NGS +

Craniosynostoses are birth defects in which one or more bone sutures on the head close earlier than usual (after 2 to 3 years of age), resulting in abnormal head shape and possibly restricted brain growth. Most children with isolated craniosynostosis are otherwise healthy with normal intelligence. However, craniosynostosis may develop in >150 genetic disorders. In inherited cases, craniosynostosis can occur along with other health problems, as in FGFR craniosynostosis syndromes. The spectrum of severity ranges from isolated unicoronal craniosynostosis to severe prenatal multisutural craniosynostosis with feeding and respiratory problems. The following FGFR craniosynostosis phenotypes are known: Apert, Beare-Stevenson-Cutis-gyrata, Crouzon [with/without acanthosis nigricans], Jackson-Weiss, Münke and Pfeiffer syndromes as well as bent-bone dysplasia and isolated coronal synostosis. Despite considerable phenotypic overlap, distinguishing features can aid in the specific diagnosis. To date, more than 500 individuals with FGFR craniosynostosis syndromes have been described. FGFR craniosynostosis syndrome is suspected in a fetus in whom the prenatal ultrasound reveals craniosynostosis with involvement of the coronal sutures, specifically a cloverleaf skull, polysyndactyly, midface retrusion and growth restriction. Bent-bone dysplasia should be suspected in a fetus that has features of skeletal dysplasia, such as a hypoplastic thorax with short ribs, short limbs, curved femurs or cranial deformity. The symptoms usually become more pronounced with age. The genes FGFR1, FGFR2, FGFR3 and TWIST1 account for more than 3/4 of the most common craniofacial syndromes; more than a dozen additional genes are implicated in the comprehensive differential diagnosis. The pattern of inheritance is often autosomal dominant, more rarely autosomal recessive or X-linked. Because DNA the yield of DNA testing is incomplete, a negative molecular genetic result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1455/

• Alias: Koronarnaht-Synostose
• Allelic: Achondroplasia (FGFR3)
• Allelic: Bladder cancer, somatic (FGFR3)
• Allelic: Brachydactyly, type A1 (IHH)
• Allelic: CATSHL syndrome (FGFR3)
• Allelic: Cardiac valvular dysplasia, XL (FLNA)
• Allelic: Cervical cancer, somatic (FGFR3)
• Allelic: Chitayat syndrome [respiratory distress, facial dysmorphism, digital anomalies] (ERF)
• Allelic: Colorectal cancer, hereditary nonpolyposis, type 6 (TGFBR2)
• Allelic: Colorectal cancer, somatic (FGFR3)
• Allelic: Congenital short bowel syndrome (FLNA)
• Allelic: Disordered steroidogenesis due to cytochrome P450 oxidoreductase (POR)
• Allelic: Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
• Allelic: Esophageal cancer, somatic (TGFBR2)
• Allelic: FG syndrome 2 (FLNA)
• Allelic: Frontometaphyseal dysplasia 1 (FLNA)
• Allelic: Heterotopia, periventricular, 1 (FLNA)
• Allelic: Hypochondroplasia (FGFR3)
• Allelic: Hypogonadotropic hypogonadism 2 with/_out anosmia (FGFR1)
• Allelic: Intestinal pseudoobstruction, neuronal (FLNA)
• Allelic: Melnick-Needles syndrome (FLNA)
• Allelic: Multiple self-healing squamous epithelioma, susceptibility to (TGFBR1)
• Allelic: Nevus, epidermal, somatic (FGFR3)
• Allelic: Pallister-Hall syndrome (GLI3)
• Allelic: Parietal foramina 1 (MSX2)
• Allelic: Parietal foramina with cleidocranial dysplasia (MSX2)
• Allelic: Polydactyly, postaxial, types A1 + B (GLI3)
• Allelic: Polydactyly, preaxial, type IV (GLI3)
• Allelic: RAPADILINO syndrome (RECQL4)
• Allelic: Rothmund-Thomson syndrome, type 2 (RECQL4)
• Allelic: SADDAN [severe achondroplasia with developmental delay + acanthosis nigricans] (FGFR3)
• Allelic: Spermatocytic seminoma, somatic (FGFR3)
• Allelic: Terminal osseous dysplasia (FLNA)
• Allelic: Thanatophoric dysplasia, type I (FGFR3)
• Allelic: Thanatophoric dysplasia, type II (FGFR3)
• Acampomelic campomelic dysplasia (SOX9)
• Acrocapitofemoral dysplasia (IHH)
• Antley-Bixler syndrome with genital anomalies + disordered steroidogenesis (POR)
• Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
• Apert syndrome (FGFR2)
• Baller-Gerold syndrome (RECQL4)
• Beare-Stevenson cutis gyrata syndrome (FGFR2)
• Bent bone dysplasia syndrome (FGFR2)
• C syndrome [Opitz trigonocephaly syndrome] (CD96)
• Campomelic dysplasia (SOX9)
• Campomelic dysplasia with autosomal sex reversal (SOX9)
• Carpenter syndrome [Acrocephalopolysyndactyly type II] (RAB23)
• Craniofacial-skeletal-dermatologic dysplasia (FGFR2)
• Craniofrontonasal dysplasia (EFNB1)
• Craniosynostosis 1 (TWIST1)
• Craniosynostosis 2 (MSX2)
• Craniosynostosis 3 (TCF12)
• Craniosynostosis 4 (ERF)
• Craniosynostosis, nonspecific (FGFR2)
• Crouzon syndrome (FGFR2)
• Crouzon syndrome with acanthosis nigricans (FGFR3)
• Greig cephalopolysyndactyly syndrome (GLI3)
• Hartsfield syndrome (FGFR1)
• Jackson-Weiss syndrome (FGFR1, FGFR2)
• LADD syndrome (FGFR2, FGFR3)
• Loeys-Dietz syndrome 1 (TGFBR1)
• Loeys-Dietz syndrome 2 (TGFBR2)
• Muenke syndrome (FGFR3)
• Osteoglophonic dysplasia (FGFR1)
• Otopalatodigital syndrome, type I (FLNA)
• Otopalatodigital syndrome, type II (FLNA)
• Pfeiffer syndrome (FGFR1, FGFR2)
• Robinow-Sorauf syndrome (TWIST1)
• Saethre-Chotzen syndrome (FGFR2)
• Saethre-Chotzen syndrome with/-out eyelid anomalies (TWIST1)
• Scaphocephaly + Axenfeld-Rieger anomaly (FGFR2)
• Scaphocephaly, maxillary retrusion + mental retardation (FGFR2)
• Shprintzen-Goldberg [craniosynostosis] syndrome (SKI)
• Sweeney-Cox s. [facial dysost., cleft palate/velopharyngeal insuff., low-set cupped ears] (TWIST1)
• Trigonocephaly 1 (FGFR1)