Monogenic hearing loss
Gene: SERAC1
Comment on publications: added publications form expert review to support phenotypeCreated: 19 Dec 2017, 11:20 a.m.
Comment on list classification: changed Red to Green from expert review and new evidence in the literatureCreated: 19 Dec 2017, 11:19 a.m.
Wortmann et al (2017) PMID: 29205472 reclassified MEGDEL syndrome to MEGDHEL syndrome, 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome (MEGDHEL) as they found that liver involvement was an additional clinical feature, so Hepatopathy was incorporated into the acronym. From a study of 67 individuals (39 previously unreported) from 59 families were included (age range 5 days - 33.4 years, median age 9 years) Wortmann et al idenitified 41 different SERAC1 biallelic variants, including 20 that have not been reported before. With exception of two families with a milder phenotype, all affected individuals show a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia was seen in more than 40% of all cases. Starting at a median age of six months muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learnt to walk (68%). 79% suffered hearing loss, 58% never learnt to speak, nearly all had significant intellectual disability (88%).Created: 19 Dec 2017, 11:18 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; MEGDEL syndrome; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; MEGDHEL syndrome
Publications
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
#614739:3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome[Failure to thrive; Hearing loss, sensorineural; Feeding problems; HypotoniaDegrading mitochondria; Psychomotor retardationPsychomotor regressionMental retardationSpasticityDystoniaExtrapyramidal symptomsSeizures (less common)Leigh syndromeLesions in the basal gangliaBrain atrophyCerebellar atrophy; Lactic acidosisHypoglycemia; Recurrent infectionsNeonatal sepsis; Increased serum lactateDefects in mitochondrial oxidative phosphorylation3-methylglutaconic aciduriaAbnormal phospholipid profileAbnormal phosphatidylglycerol profile (increased 34-to-1 and decreased 36-to-1 ratio)Abnormal cardiolipin subspecies compositionIntracellular accumulation of unesterified cholesterolDecreased serum cholesterol (in some)Elevated serum transaminase levelsHyperammonemiaElevated serum alpha-fetoproteinCoagulopathy (INR = 2.2 - 3.5)]
Publications
Phenotypes for gene: SERAC1 were changed from 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; MEGDEL syndrome; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; MEGDHEL syndrome to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739
Phenotypes for SERAC1 were set to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; MEGDEL syndrome; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; MEGDHEL syndrome
Publications for SERAC1 were set to 29205472; 22683713; 16527507; 28482397; 28778788; 27186703; 27604308; 23707711; 16527507
Mode of inheritance for SERAC1 was changed from to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
SERAC1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen