IllnessAnophthalmia, microphthalmia: differential diagnosis

NGS +

[Sanger]

In microphthalmia/anophthalmia, one or both eyeballs are particularly small or missing completely. Microphthalmia may or may not result in significant vision loss. The patients may have unilateral or bilateral colobomas that also impair vision. Affected individuals have sometimes other ocular abnormalities, including cataracts, narrowed palpebral fissures and microcornea. In 30-50% of the affected, microphthalmia is syndromic. The disorder can be caused by alterations in many genes involved in early eye development, most of which have not yet been identified. Many genetic alterations associated with isolated microphthalmia have been identified only in very few patients. In addition, microphthalmia can also be caused by environmental factors, such as deficiency of certain vitamins during pregnancy, radiation, infections or by exposure to teratogens. Isolated microphthalmia is sometimes inherited in an autosomal recessive manner, sometimes with decreased penetrance. In syndromal cases, microphthalmia may be clustered according to the inheritance pattern for this condition. Often microphthalmia is not inherited, only one affected person exists per family. Therefore, a negative molecular genetic result does not exclude the clinical diagnosis.

Exemplary references: https://www.ncbi.nlm.nih.gov/books/NBK1300/

https://www.ncbi.nlm.nih.gov/books/NBK7041/

https://www.ncbi.nlm.nih.gov/books/NBK1728/

• Alias: Anophthalmia-microphthalmia syndrome
• Alias: Anophthalmos, microphthalmos
• Alias: Microphthalmia-anophthalmia-coloboma
• Allelic: Aniridia (PAX6)
• Allelic: Aortic aneurysm, familial thoracic 11, susceptibility to (FOXE3)
• Allelic: Basal cell nevus syndrome (PTCH1)
• Allelic: Bifid nose with/-out anorectal + renal anomalies (FREM1)
• Allelic: CHARGE [Coloboma, Heart anom., choanal Atresia, Retard., Genital/Ear anom.] syndrome (CHD7)
• Allelic: Cardiac-urogenital syndrome (MYRF)
• Allelic: Cataract 34, multiple type (FOXE3)
• Allelic: Cataract 40, XL (NHS)
• Allelic: Cataract with late-onset corneal dystrophy (PAX6)
• Allelic: Coloboma of optic nerve (PAX6)
• Allelic: Coloboma, ocular (PAX6)
• Allelic: Encephalitis/encephalopathy, mild, reversible myelin vacuolization (MYRF)
• Allelic: Facioscapulohumeral muscular dystrophy 2, digenic (SMCHD1)
• Allelic: Foveal hypoplasia 1 (PAX6)
• Allelic: Glomerulosclerosis, focal segmental, 7 (PAX2)
• Allelic: Growth hormone deficiency with pituitary anomalies (HESX1)
• Allelic: Holoprosencephaly 3 (SHH)
• Allelic: Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
• Allelic: Keratitis (PAX6)
• Allelic: Klippel-Feil syndrome 1, AD (GDF6)
• Allelic: Klippel-Feil syndrome 3, AD (GDF3)
• Allelic: Leber congenital amaurosis 17 (GDF6)
• Allelic: Linear skin defects with multiple congenital anomalies 1 (HCCS)
• Allelic: Morning glory disc anomaly (PAX6)
• Allelic: Multiple synostoses syndrome 4 (GDF6)
• Allelic: Nance-Horan [cataract-dental] syndrome (NHS)
• Allelic: Ogden syndrome [growth failure, delayed psychomotor development, dysmorphisms] (NAA10)
• Allelic: Optic disc anomalies with retinal and/or macular dystrophy (SIX6)
• Allelic: Optic nerve hypoplasia (PAX6)
• Allelic: Pallister-Hall-like syndrome (SMO)
• Allelic: Persistent hyperplastic primary vitreous, AR (ATOH7)
• Allelic: Pituitary hormone deficiency, combined, 5 (HESX1)
• Allelic: Pituitary hormone deficiency, combined, 6 (OTX2)
• Allelic: Retinal dystrophy, early-onset, with/-out pituitary dysfunction (OTX2)
• Allelic: Ring dermoid of cornea (PITX2)
• Allelic: Schizencephaly (SHH)
• Allelic: Single median maxillary central incisor (SHH)
• Allelic: Temtamy syndrome [Ment. retard., craniofacial dysmorph., coloboma] (C13orf57)
• Allelic: Trigonocephaly 2 (FREM1)
• Anophthalmia (PAX6)
• Anophthalmia, microphthalmia (RAX, SIX6)
• Anterior segment dysgenesis 2, multiple subtypes (FOXE3)
• Anterior segment dysgenesis 3, multiple subtypes (FOXC1)
• Anterior segment dysgenesis 4 (PITX2)
• Anterior segment dysgenesis 5, multiple subtypes (PAX6)
• Anterior segment dysgenesis 7, with sclerocornea (PXDN)
• Axenfeld-Rieger syndrome, type 1 (PITX2)
• Axenfeld-Rieger syndrome, type 3 (FOXC1)
• BMP4-Related Syndromic Microphthalmia (BMP4)
• Bilateral microphthalmia, short stature + facial dysmorphism [panelapp] (OLFM2)
• Bosma arhinia microphthalmia syndrome (SMCHD1)
• Branchiooculofacial syndrome (TFAP2A)
• Cataract 9, multiple types (CRYAA)
• Cerebrooculofacioskeletal syndrome 4 (ERCC1)
• Coloboma, ocular, AR (SALL2)
• Coloboma, ocular, with/-out hearing impairment, cleft lip/palate, mental retardation (YAP1)
• Colobomatous microphthalmia [panelapp] (FAT1)
• Curry-Jones syndrome, somatic mosaic (SMO)
• Focal dermal hypoplasia (PORCN)
• Fraser syndrome 3 [cryptophthalmus + other malformations] (GRIP1)
• Fraser syndrome [cryptophthalmus + other malformations] (FRAS1)
• Holoprosencephaly 7 (PTCH1)
• Isolated Microphthalmia (MFRP)
• Joubert syndrome 22 (PDE6D)
• Kabuki syndrome 1 (KMT2D)
• Manitoba oculotrichoanal syndrome (FREM1)
• Martsolf [cataract-mental retardation-hypogonadism] syndrome (RAB3GAP2)
• Microphthalmia with cataract 2 (SIX6)
• Microphthalmia with coloboma 3 (VSX2)
• Microphthalmia with coloboma 5 (SHH)
• Microphthalmia with coloboma 6 (GDF3)
• Microphthalmia with coloboma 6, digenic (GDF6)
• Microphthalmia with limb anomalies (SMOC1)
• Microphthalmia, Kabuki syndrome 1 (KMT2D)
• Microphthalmia, coloboma, micrognathia, diaphragmatic hernia [panelapp] (TMX3)
• Microphthalmia, isolated 2 (VSX2)
• Microphthalmia, isolated 3 (RAX)
• Microphthalmia, isolated 4 (GDF6)
• Microphthalmia, isolated 5 (MFRP)
• Microphthalmia, isolated 6 (PRSS56)
• Microphthalmia, isolated 7 (GDF3)
• Microphthalmia, isolated 8 (ALDH1A3)
• Microphthalmia, isolated, with coloboma 7 (ABCB6)
• Microphthalmia, isolated, with coloboma 8 (STRA6)
• Microphthalmia, isolated, with coloboma 9 (TENM3)
• Microphthalmia, syndromic 1 (NAA10)
• Microphthalmia, syndromic 11 (VAX1)
• Microphthalmia, syndromic 13 (HMGB3)
• Microphthalmia, syndromic 14 (MAB21L2)
• Microphthalmia, syndromic 15 (TENM3)
• Microphthalmia, syndromic 2 (BCOR)
• Microphthalmia, syndromic 3 (SOX2)
• Microphthalmia, syndromic 5 (OTX2)
• Microphthalmia, syndromic 6 (BMP4)
• Microphthalmia, syndromic 7 (HCCS)
• Microphthalmia, syndromic 9 (STRA6)
• Microphthalmia/coloboma + skeletal dysplasia syndrome (MAB21L2)
• Nanophthalmos 2 (NFRP)
• Nanophthalmos 4 (TMEM98)
• Nanophthalmos [panelapp] (MYRF)
• Nanophthalmos, high hyperopia (MYRF)
• OTX2-related syndromic microphthalmia 4 (OTX2)
• Oculogastrointestinal neurodevelopmental syndrome (CAPN15)
• Optic nerve hypoplasia and abnormalities of the central nervous system (SOX2)
• Orofaciodigital syndrome IX [panelapp] (SCLT1)
• Papillorenal [renal coloboma] syndrome (PAX2)
• Renpenning [mental retardation, XL syndromic] syndrome (PQBP1)
• Septooptic dysplasia [optic nerve hypopl., pituitary hypoplasia, midline brain anomalies] (HESX1)
• Warburg micro syndrome 1 (RAB3GAP1)
• Warburg micro syndrome 12 (RARB)
• Warburg micro syndrome 2 (RAB3GAP2)
• Warburg micro syndrome 3 (RAB18)
• Warburg micro syndrome 4 (TBC1D20)