IllnessGoldenhar syndrome/hemifacial microsomia, differential diagnosis

NGS +

The Oculo-Auriculo-Vertebral Spectrum (OAVS) includes three rare congenital disorders. Oculo-auriculo-vertebral disorder represents the mildest form, while Goldenhar syndrome is most severe and Hemi-Facial Microstomia (HFM) is an intermediate form. OAVS is characterized by a wide range of symptoms, and physical features can vary widely. OAVS can affect the cheekbones, jaw, mouth, ears, eyes, and/or spine. Although unilateral in ~60%, such malformations may also manifest bilaterally with asymmetry, the right side more affected. In HFM, only the right side is usually affected, and both the jaw and eye may be much smaller, with microtia/annotia and hearing loss without intellectual deficits. Patients with Goldenhar sydrome show most or all HFM symptoms, in ≤33% of cases, symptoms are bilateral. Cleft lip and/or palate may be present. Tongue and cheek muscles may cause severe speech disorders. Colobomas, dermoid cysts, heart defects, and kidney problems are also observed; intelligence is not affected. OAVS more commonly affects males. Differential diagnosis includes Duane, Townes-Brocks, Treacher Collins, and 22q11.2 deletion syndromes, as well as autosomal recessive spondylocostal dysostosis and mandibulo-facial dysostosis with microcephaly. In most cases OAVS occurs sporadically, in some cases the inheritance is autosomal dominant or recessive. Although extensive molecular genetic diagnostics clarify some cases, the diagnostic yield is unknown. A negative DNA test result excludes the diagnosis of OAVS by no means.

References: https://www.ncbi.nlm.nih.gov/books/NBK1190/

https://www.ncbi.nlm.nih.gov/books/NBK1445/

https://www.ncbi.nlm.nih.gov/books/NBK1532/

https://www.ncbi.nlm.nih.gov/books/NBK1523/

https://www.ncbi.nlm.nih.gov/books/NBK8828/

https://www.ncbi.nlm.nih.gov/books/NBK214367/

• Alias preferred in guidelines: Craniofacial microsomia
• Alias: Facio-auriculo-vertebral syndrome; Facioauriculovertebral sequence
• Alias: First + second branchial arch syndrome; First arch syndrome; Goldenhar disease
• Alias: Oculoauriculovertebral dysplasia; Otomandibular Dysostosis
• Alias: Auricuo-oculo-vertebral spectrum
• Alias: Deafness, hearing impairment
• Alias: Ear malformations with hearing impairment
• Alias: Goldenhar disease
• Alias: Microtia
• Alias: Schwerhörigkeit, Taubheit
• Allelic: Achondroplasia (FGFR3)
• Allelic: Anemia, sideroblastic, 4 (HSPA9)
• Allelic: Anterior segment anomalies with/-out cataract (EYA1)
• Allelic: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
• Allelic: Apert syndrome (FGFR2)
• Allelic: Aplasia of lacrimal and salivary glands (FGF10)
• Allelic: Beare-Stevenson cutis gyrata syndrome (FGFR2)
• Allelic: Bent bone dysplasia syndrome (FGFR2)
• Allelic: Bladder cancer, somatic (FGFR3)
• Allelic: CATSHL syndrome (FGFR3)
• Allelic: Cervical cancer, somatic (FGFR3)
• Allelic: Colorectal cancer, somatic (FGFR3)
• Allelic: Craniofacial-skeletal-dermatologic dysplasia (FGFR2)
• Allelic: Craniosynostosis, nonspecific (FGFR2)
• Allelic: Crouzon syndrome (FGFR2)
• Allelic: Crouzon syndrome with acanthosis nigricans (FGFR3)
• Allelic: Cryptophthalmos, unilateral or bilateral, isolated (FREM2)
• Allelic: Duane-radial ray syndrome (SALL4)
• Allelic: Gastric cancer, somatic (FGFR2)
• Allelic: Hypochondroplasia (FGFR3)
• Allelic: Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
• Allelic: Jackson-Weiss syndrome (FGFR2)
• Allelic: Leber congenital amaurosis 17 (GDF6)
• Allelic: Leukodystrophy, hypomyelinating, 11 (POLR1C)
• Allelic: Microphthalmia with coloboma 6, digenic (GDF6)
• Allelic: Microphthalmia, isolated 4 (GDF6)
• Allelic: Migraine, resistance to (EDNRA)
• Allelic: Muenke syndrome (FGFR3)
• Allelic: Multiple synostoses syndrome 4 (GDF6)
• Allelic: Nevus, epidermal, somatic (FGFR3)
• Allelic: PCWH syndrome (SOX10)
• Allelic: Pfeiffer syndrome (FGFR2)
• Allelic: Retinal dystrophy, early-onset, with/-out pituitary dysfunction (OTX2)
• Allelic: Retinitis pigmentosa 23 (OFD1)
• Allelic: SADDAN (FGFR3)
• Allelic: Saethre-Chotzen syndrome (FGFR2)
• Allelic: Scaphocephaly + Axenfeld-Rieger anomaly (FGFR2)
• Allelic: Scaphocephaly, maxillary retrusion + mental retardation (FGFR2)
• Allelic: Spermatocytic seminoma, somatic (FGFR3)
• Allelic: Thanatophoric dysplasia, type I + II (FGFR3)
• Acrofacial dysostosis 1, Nager type (SF3B4)
• Acrofacial dysostosis, Cincinnati type (POLR1A)
• Athabaskan brainstem dysgenesis syndrome (HOXA1)
• Auriculocondylar syndrome 1 (GNAI3)
• Auriculocondylar syndrome 2 (PLCB4)
• Bosley-Salih-Alorainy syndrome (HOXA1)
• Branchiooculofacial syndrome (TFAP2A)
• Branchiootic syndrome 1 (EYA1)
• Branchiootic syndrome 3 (SIX1)
• Branchiootorenal syndrome 1, with/-out cataracts (EYA1)
• Branchiootorenal syndrome 2 (SIX5)
• CHARGE syndrome (CHD7)
• Craniofacial microsomia (SF3B2)
• Deafness, AD 23 (SIX1)
• Deafness, AR 4, with enlarged vestibular aqueduct (SLC26A4)
• Deafness, congenital with inner ear agenesis, microtia + microdontia (FGF3)
• Diamond Blackfan anemia 15 with mandibulofacial dysostosis (RPS28)
• Ear malformations with hearing impairment (CDT1)
• Even-plus syndrome (HSPA9)
• Fraser syndrome 1 (FRAS1)
• Fraser syndrome 2 (FREM2)
• Fraser syndrome 3 (GRIP1)
• IVIC syndrome (SALL4)
• Joubert syndrome 10 (OFD1)
• Kabuki syndrome 1 (KMT2D)
• Kabuki syndrome 2 (KDM6A)
• Klippel-Feil syndrome 1, AD (GDF6)
• LADD syndrome (FGF10, FGFR2, FGFR3)
• Mandibulofacial dysostosis with alopecia (EDNRA)
• Mandibulofacial dysostosis, Guion-Almeida type (EFTUD2)
• Meier-Gorlin syndrome 1 (ORC1)
• Meier-Gorlin syndrome 2 (ORC4)
• Meier-Gorlin syndrome 3 (ORC6)
• Meier-Gorlin syndrome 5 (CDC6)
• Microphthalmia, syndromic 5 (OTX2)
• Microphthalmia, syndromic 6 (BMP4)
• Microtia with/-out hearing impairment, AD (HOXA2)
• Microtia, hearing impairment + cleft palate, AR (HOXA2)
• Miller syndrome (DHODH)
• Oculoauricular syndrome (HMX1)
• Orofacial cleft 11 (BMP4)
• Orofaciodigital syndrome I (OFD1)
• Otofaciocervical syndrome (EYA1)
• Pendred syndrome (SLC27A4)
• Pituitary hormone deficiency, combined, 6 (OTX2)
• Robin sequence with cleft mandible + limb anomalies (EIF4A3)
• Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities (GSC)
• Simpson-Golabi-Behmel syndrome, type 2 (OFD1)
• Townes-Brocks branchiootorenal-like syndrome (SALL1)
• Townes-Brocks syndrome 1 (SALL1)
• Treacher Collins syndrome 1 (TCOF1)
• Treacher Collins syndrome 2 (POLR1D)
• Treacher Collins syndrome 3 (POLR1C)
• Waardenburg syndrome, type 2E, with/-out neurologic involvement (SOX10)
• Waardenburg syndrome, type 4C (SOX10)