Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Providing clinically relevant prognoses and treatment information for people with a chromsome18q deletion is particularly challenging because every unrelated person has a unique region of hemizygosity. The hemizygous region can involve almost any region of 18q including between 1 and 101 genes (30 Mb of DNA). Most individuals have terminal deletions, but in our cohort of over 350 individuals 23% have interstitial deletions. Because of this heterogeneity, we take a gene by gene approach to understanding the clinical consequences. There are 196 genes on 18q. We classified 133 of them as dosage insensitive, 15 (8%) as dosage sensitive leading to haploinsufficiency while another 10 (5%) have effects that are conditionally haploinsufficient and are dependent on another factor, genetic or environmental in order to cause an abnormal phenotype. Thirty-seven genes (19%) have insufficient information to classify their dosage effect. Phenotypes attributed to single genes include: congenital heart disease, minor bone morphology changes, central nervous system dysmyelination, expressive speech delay, vesicouretreral reflux, polyposis, Pitt-Hopkins syndrome, intellectual disability, executive function impairment, male infertility, aural atresia, and high frequency sensorineural hearing loss. Additionally, identified critical regions for other phenotypes include: adolescent idiopathic scoliosis and pectus excavatum, Virchow-Robin perivascular spaces, small corpus callosum, strabismus, atopic disorders, mood disorder, IgA deficiency, nystagmus, congenital heart disease, kidney malformation, vertical talus, CNS dysmyelination growth hormone deficiency and cleft palate. Together these findings make it increasingly feasible to compile an individualized syndrome description based on each person's individuated genotype. Future work will focus on understanding molecular mechanisms leading to treatment.
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PMID:Consequences of chromsome18q deletions. 2623 40

Whole-exome sequencing has established IQSEC2 as a neurodevelopmental disability gene. The IQSEC2 variant phenotype includes developmental delay, intellectual disability, epilepsy, hypotonia, autism, developmental regression, microcephaly and stereotypies but is yet to be fully described. Presented here are 14 new patients with IQSEC2 variants. In addition to the established features, we observed: gait ataxia in 7 of 9 (77.8%), drooling in 9 of 14 (64.2%), early feeding difficulties in 7 of 14 (50%), structural brain abnormalities in 6 of 13 (46.2%), brachycephaly in 5 of 14 (35.7%), and scoliosis and paroxysms of laughter each in 4 of 14 (28.6%). We suggest that these are features of the IQSEC2-related disorder. Gastrostomy requirement, plagiocephaly, strabismus and cortical blindness, each seen in 2 of 14 (14.3%), may also be associated. Shared facial features were noted in 8 of 14 patients, and shared hair patterning was identified in 5 of 14 patients. This study further delineates the IQSEC2 phenotypic spectrum and supports the notion of an emerging IQSEC2 syndrome. We draw parallels between the IQSEC2-related disorder and the Angelman-/Rett-/Pitt-Hopkins syndrome group of conditions and recommend the addition of IQSEC2 to epilepsy and developmental delay gene panels. We observed discordant phenotypes in monozygotic twins and apparent gonadal mosaicism, which has implications for recurrence risk counselling in the IQSEC2-related disorder.
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PMID:Deep phenotyping of 14 new patients with IQSEC2 variants, including monozygotic twins of discordant phenotype. 3066 32