IllnessNystagmus, infantile; differential diagnosis

NGS +

Infantile nystagmus syndrome (INS) can occur in isolation or as part of a variety of ocular or systemic disorders, including albinism, retinal disorders and neurologic disorders. Nystagmus may be present at birth or develop within the first six months of life. Eye movements may worsen if the affected person is anxious or tries to stare directly at an object. The severity of nystagmus varies, even among affected individuals within the same family. Sometimes affected individuals turn or tilt their head to compensate for the irregular eye movements. Although FRMD7 gene mutations are the only known genetic cause of idiopathic INS to date, there are many disorders that can masquerade as nystagmus in children. These disorders are often overlooked, because it is difficult to identify associated phenotypes (such as hypomorphic albinism) or because additional clinical features, such as spinocerebellar ataxia, appear late. All Mendelian inheritance patterns can be observed, as mutations in several different genes cause INS. Yet no mutations have been identified in some INS patients, so the diagnostic yield is currently 40-60%, which depends largely on panel composition and detailed clinical characterization. Therefore, the clinical diagnosis is not ruled out by a negative DNA test result.

References: https://www.ncbi.nlm.nih.gov/books/NBK3822/

https://www.nature.com/articles/s41598-019-49368-7#MOESM1/

• Allelic: Epileptic encephalopathy, early infantile, 42 (CACNA1A)
• Allelic: Melanoma, cutaneous malignant, susceptibility to, 8 (TYR)
• Allelic: Migraine, familial hemiplegic, 1 (CACNA1A)
• Allelic: Skin/hair/eye pigmentation 1, blond/brown hair (OCA2)
• Allelic: Skin/hair/eye pigmentation 1, blue/nonblue eyes (OCA2)
• Allelic: Skin/hair/eye pigmentation 3, blue/green eyes (TYR)
• Allelic: Skin/hair/eye pigmentation 3, light/dark/freckling skin (TYR)
• Allelic: Skin/hair/eye pigmentation 4, fair/dark skin (SLC24A5)
• Allelic: Skin/hair/eye pigmentation 5, black/nonblack hair (SCL45A2)
• Allelic: Skin/hair/eye pigmentation 5, dark/fair skin (SLC45A2)
• Allelic: Skin/hair/eye pigmentation 5, dark/light eyes (SLC45A2)
• Allelic: Skin/hair/eye pigmentation, variation in, 11 [Melanesian blond hair] (TYRP1)
• Aland Island eye disease (CACNA1F)
• Albinism, brown oculocutaneous (OCA)
• Albinism, oculocutaneous, type IA + IB (TYR)
• Albinism, oculocutaneous, type II (OCA2)
• Albinism, oculocutaneous, type III (TYRP1)
• Albinism, oculocutaneous, type IV (SLC45A2)
• Albinism, oculocutaneous, type VI (SLC24A5)
• Albinism, oculocutaneous, type VII (LRMDA)
• Allelic: Amyotrophic lateral sclerosis 4, juvenile (SETX)
• Allelic: Aniridia (PAX6)
• Allelic: Anterior segment dysgenesis 5, multiple subtypes (PAX6)
• Allelic: Cataract with late-onset corneal dystrophy (PAX6)
• Allelic: Coloboma of optic nerve (PAX6)
• Allelic: Coloboma, ocular (PAXY6)
• Allelic: Keratitis (PAX6)
• Allelic: Morning glory disc anomaly (PAX6)
• Allelic: Optic nerve hypoplasia (PAX6)
• Allelic: Retinitis pigmentosa 14 (TULP1)
• Chediak-Higashi syndrome (LYST)
• Cone-rod dystrophy, XL, 3 (CACNA1F)
• Episodic ataxia, type 2 (CACNA1A)
• FG syndrome 4 (CASK)
• Foveal hypoplasia 1 (PAX6)
• Foveal hypoplasia 2, +/- optic nerve misrouting +/+ anterior segment dysgenesis (SLC38A8)
• Intellectual developmental disorder + microcephaly with pontine + cerebellar hypoplasia (CASK)
• Leber congenital amaurosis 15 (TULP1)
• Mannosidosis, beta (MANBA)
• Mental retardation, with or without nystagmus (CASK)
• Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia (CACNA1A)
• Night blindness, congenital stationary (incomplete), 2A, XL (CACNA1F)
• Night blindness, congenital stationary, complete, 1A, XL (NYX)
• Nystagmus 1, congenital, XL (FRMD7)
• Nystagmus 6, congenital, XL (GPR143)
• Nystagmus, infantile periodic alternating, XL (FRMD7)
• Ocular albinism, type I, Nettleship-Falls type (GPR143)
• Retinitis pigmentosa 85 (AHR)
• Spastic ataxia, Charlevoix-Saguenay type (SACS)
• Spinocerebellar ataxia 6 (CACNA1A)
• Spinocerebellar ataxia, AR, with axonal neuropathy 2 (SETX)
• Waardenburg syndrome/albinism, digenic (TYR)