Imprinting disorders Notes

Contents

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Imprinting disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Imprinting disorders by visiting the associated Learn Page.
Chapter 2 Acyanotic Defects NOTES IMPRINTING DISORDERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Genetic, epigenetic mutations/defects within imprinting controlling regions of genes ▪ Disruption of methylation of cytosine bases in CpG dinucleotides of DNA RISK FACTORS ▪ Increased incidence in individuals conceived using assisted reproductive technology SIGNS & SYMPTOMS ▪ Angelman syndrome ▫ Seizures, severe intellectual disability, jerky/tremulous limbs, characteristic facial appearance (e.g. large mouth, protruding tongue, prominent nose), excitability, impaired speech ▪ Beckwith–Wiedemann syndrome ▫ Premature birth, abdominal wall defects, embryonal tumors ▪ Prader–Willi syndrome ▫ Infancy: poor feeding, low muscle tone, weak cry, diminished reflexes ▫ Early childhood obesity, developmental delay, behavioral problems ▫ Dysmorphic facial features DIAGNOSIS OTHER DIAGNOSTICS ▪ History, clinical examination ▪ Fluorescence in situ hybridization (FISH), genotyping, methylation DNA testing ▪ Methylation-sensitive multiplex ligation probe analysis (MS-MLPA) TREATMENT MEDICATIONS ▪ Angelman syndrome: antiepileptic therapy ▪ Prader–Willi syndrome: thyroid, sex hormone replacement therapy OTHER INTERVENTIONS ▪ Angelman syndrome: speech therapy ▪ Beckwith–Wiedemann syndrome: tumor surveillance, abdominal wall repair ▪ Prader–Willi syndrome: food restriction, vitamin D/calcium supplements OSMOSIS.ORG 169
ANGELMAN SYNDROME osms.it/angelman-syndrome PATHOLOGY & CAUSES ▪ Genetic neurological disorder; severe developmental delay, intellectual disability, absence of speech, ataxia, dysmorphic features, unprovoked episodes of laughter CAUSES ▪ Maternal 15q11-q13 deletion ▪ Loss of function of UBE3A ▪ Paternal uniparental disomy 15 (both copies of chromosome 15 from father) SIGNS & SYMPTOMS ▪ Seizures, severe intellectual disability ▪ Ataxia, toe-walking, jerky/tremulous limbs ▪ Hypopigmentation, microcephaly, maxillary hypoplasia, large mouth, protruding tongue, prominent nose, wide-spaced teeth ▪ Inappropriate laughter (“happy puppet”), excitability, impaired speech 170 OSMOSIS.ORG DIAGNOSIS OTHER DIAGNOSTICS ▪ FISH, genotyping, methylation DNA testing TREATMENT MEDICATIONS ▪ Antiepileptic therapy for seizures OTHER INTERVENTIONS ▪ Speech therapy; emphasis on nonverbal methods of communication
Chapter 26 Imprinting Disorders BECKWITH–WIEDEMANN SYNDROME osms.it/beckwith-wiedemann_syndrome PATHOLOGY & CAUSES ▪ Pediatric overgrowth syndrome; visceromegaly, predisposition to tumors CAUSES ▪ Error in imprinted gene expression in chromosome 11p15.5 region ▪ Usually sporadic, may be inherited in autosomal dominant fashion SIGNS & SYMPTOMS Fetal macrosomia, premature birth Macroglossia Renal medullary hyperplasia Abdominal wall defects ▫ Omphalocele, umbilical hernia, diastasis recti ▪ Hypoglycemia due to islet cell hyperplasia ▪ Puberty, episeal fusion (early symptoms) ▪ Embryonal tumors (e.g. Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma) ▪ ▪ ▪ ▪ DIAGNOSIS OTHER DIAGNOSTICS ▪ Clinical diagnosis ▪ MS-MLPA ▫ Detect majority of epigenetic, genetic etiologies TREATMENT OTHER INTERVENTIONS ▪ Tumor surveillance with abdominal MRI/CT scan ▪ Abdominal wall repair for omphalocele ▪ Assess, treat airway insufficiency; feeding evaluation in presence of macroglossia ▪ Assess, treat hypoglycemia for neonates OSMOSIS.ORG 171
PRADER–WILLI SYNDROME osms.it/prader-willi_syndrome PATHOLOGY & CAUSES ▪ Genetic multisystem disorder; weak muscle tone; delayed growth, development; behavioral abnormalities (e.g. insatiable hunger) CAUSES ▪ Paternal 15q11-q13 deletion (maternal gene unchanged) ▪ Maternal uniparental disomy 15 (both copies of chromosome 15 from mother) ▪ Defects in imprinting center controlling chromosome 15 activity of genes ▪ Associated with dysregulation of hypothalamic-pituitary axis COMPLICATIONS ▪ Sleep apnea (central/obstructive), scoliosis, osteoporosis, hypothyroidism, Type II diabetes SIGNS & SYMPTOMS ▪ Infancy ▫ Poor feeding, low muscle tone, weak cry, diminished reflexes ▪ Overeating (hyperphagia), early childhood obesity ▪ Developmental delay ▫ Intellectual disability; delayed motor, language development ▪ Behavioral problems ▫ Inflexibility, obsessive-compulsive characteristics ▪ Low sex hormones in childhood, hypogenitalism/hypogonadism; cryptorchidism in individuals who are biologically male 172 OSMOSIS.ORG ▪ Dysmorphic facial features in childhood ▫ Almond-shaped eyes, narrow forehead, thin upper lip ▪ Small hands/feet, short stature DIAGNOSIS OTHER DIAGNOSTICS ▪ History, clinical examination ▪ Fluorescence in situ hybridization (FISH), genotyping, methylation DNA testing TREATMENT MEDICATIONS ▪ Human recombinant growth hormone therapy ▫ Decrease body weight/fat, increase muscle mass ▪ Address complications ▫ Thyroid, sex hormone replacement therapy OTHER INTERVENTIONS ▪ Food restriction ▪ Address complications ▫ Vitamin D, calcium supplements

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Imprinting disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Imprinting disorders by visiting the associated Learn Page.