Ring 18 04/2017. Mosaicism (N=30) No mosaicism 53% Ring18/ monosomy 18 27% Ring 18/ der 18 13% Ring 18/ nl 18 3% Ring 18/ nl 18/ mono 18 3%
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- Gervais Ray
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1 04/2017 Ring 18 Mosaicism (N=30) No mosaicism 53% Ring18/ monosomy 18 27% Ring 18/ der 18 13% Ring 18/ nl 18 3% Ring 18/ nl 18/ mono 18 3% % GH deficiency 93 Hypotonia 92 Hearing Loss 80 Chronic otitis media 74 Microcephaly 70 Reflux 68 Respiratory difficulties 67 Hyperopia 67 Feeding difficulties 61 Constipation 58 Narrow ear canals 50 Strabismus 47 Hypothyroid 41 pulmonary stenosis 38 Ptosis 38 Jaundice 37 % Scoliosis/kyphosis 31 G or NG tube/ dysphagia 30 Seizures 26 Atrial septal defect 25 Nystagmus 20 Cleft palate 19 patent foramen ovale 17 Metatarsus aductus 13 Asthma 13 patent ductus arteriosus 12 Vertical talus 10 Bifid uvula 10 Club feet 9 Astigmatism 8 Pes cavus 7 Overlapping toes 7 Pectus excavatum 4
2 Behavior : Adults (BASC-2) n=5 Common problem: Evading others to avoid social contact 60% No problems identified Hostile threatening behaviors Anti-social and rule-breaking behaviors Social Impairment (SRS-2) (ages ) n=12 Common problems: Picking up social cues 92% Interpreting social cues 83% Social communication 83% Motivated to engage in social behavior 67% Repetitive behaviors / obsessing same routines 58% Social Impairment (SRS-2) (adults) n=5 Common problems: Interpreting social cues 80% Repetitive behaviors /obsessing same routines 60% Natural History (>age 18) n=7 Living Situation: Home with parents 4 With parents in independent area 2 Unknown 1 Highest Educational Level: Attending High School 1 High School Graduate (diploma) 1 Currently attends college 1 Vocational School (certificate/degree) 1 Some College/University (no degree) 1 Marital Status/Children Married (no) 5 Married (unknown) 2 Children (none) 5 Children (unknown) 2 Work (Volunteer, Part-time, Full-time): Yes 3 No 2 Less common problems: Picking up social cues 20% Executive Functioning: Adults (BRIEF-A) n=5 : Keeping track of own problem solving successes or failure 60% Managing current and future oriented tasks 60% Less common problems Acting on an impulse 20% Understanding their effect on others 20% Begin a task independently 20% Keep work and living spaces orderly and organized 20%
3 Ring 18: Current Ages & Age at Death Deceased Current Age Age in Years Age deceased Gender Cause of death Past medical history 4 years 5 months 5 years 1 month 5 years 8 months F F F Lung failure Had been vomiting prior to death. No acute cause of death. Had not been ill for the last 9 months Congenital heart disease; chronic lung disease; congestive heart failure ASD; seizures; cerebellar stroke; coloboma of Iris; spastic quadriparesis; pulmonary hypertension; respiratory insufficiency; obstructive sleep apnea; aspiration pneumonia; GERD; asthma Hydrocephalus; severe hypotonia; poor cough reflex with hypoventilation; used to have heart failure Complex congenital heart disease; history of seizures; cleft palate; G tube and fundoplication; partial agenesis of corpus callosum; chronic lung disease; tendency for hypoglycemia; optic atrophy
4 18q 04/2017
5 Proximal 18q No recognizable facial features Mild global developmental delay Normal birth weight Poor muscle tone Normal growth More severe expressive language delay 2 with larger deletions had hearing loss 18q- Natural History 4 individuals age 18 and over Living Situation: Live with their parents/guardians 2 Martial Status/Children: Never married 2 No children 2 Work (Volunteer, Part-time, Full-time): Yes 1 No 1 Behavior- Adults (BASC-2) n=2 Performing basic tasks safely 100% Overly active, acting without thinking 100% Odd behaviors 100% Antisocial & rule breaking behaviors 100% Inability to adapt to change 100% No Problems Avoiding social contact 0% Interacting with peers 0% Ability to work for a common goal 0% Highest educational level: Did Not Complete High School 1 High School Graduate (certificate) 1 Social Impairment Ages (SRS-2) n=4 Repeating behaviors /obsessing over routines 100% Expressing social communication 100% Interpreting Social Cues 75% Motivation to Engage in Social Behavior 75% Inability to pick up on social cues 50% Social Impairment - Adults (SRS-2) n=2 Interpreting social cues 100% Repeating behaviors /obsessing over the routines 100% Inability to pick up on social cues 100% No problems Motivation to engage in social behavior 0% Executive Functioning in Adults (BRIEF A) n=2 Keeping track of problem solving successes or failures 100% Remembering information in order to complete a task 100% Move from one situation to another 100% Beginning tasks 100% Managing current & future oriented tasks 100% Inhibiting behavior or not act on an impulse 100% Understand the effect of behaviors on others 100% Keeping work & living spaces orderly 100% Modulating emotional response 100%
6 Adults with Proximal 18q Potential conditions in a neonate Structural Palate abnormality Functional Respiratory difficulties Feeding difficulties Central apnea Hypotonia Biochemical Jaundice Initial evaluations Cardiology evaluation 50% have cardiac defects Hearing evaluation 30% with hearing deficits Renal ultrasound 43% with reflux Vision evaluation 64% with optic problems MRI 62% abnormal findings Referrals to Appropriate subspecialist as indicated by initial evaluations Genetics Follow up Parents genotyped for balanced rearrangements Early intervention/developmental services The Chromosome 18 Registry & Research Society The Chromosome 18 Clinical Research Center Closely monitor and manage Failure to thrive/ growth failure Weight gain Linear growth Sinus/ ear infections Genitourinary: Reflux Gastrointestinal Immunology/Rheumatology: Atopic disorders Orthopedics Scoliosis Respiratory issues Neurology: Seizure disorder Tremors hypotonia Development: Milestones Speech delay School performance Behavioral/ mood changes Annual Screenings Vision Hearing
7 Distal18q with TCF4 deletion 18q- Natural History 13 individuals age 18 and over Living Situation: Live with their parents/guardians 8 Group home 3 Martial Status/Children: Never married 11 No children 11 Work (Volunteer, Part-time, Full-time): Yes 1 No 10 Highest educational level: Did Not Complete High School 4 Attending high school 2 High School Graduate (certificate) 5 Behavior- Adults (BASC-2) n=9 Performing basic tasks safely 100% Expressing ideas in a way understood by others 100% Interacting with peers 100% Less Nervous, fearful and worrisome tendencies 11% Acting in a hostile, threatening manner 11% Incapacitating sadness or stress 11% Behaving overly sensitive about minor problems 11% Social Impairment - Adults (SRS-2) n=6 Expressing social communication 100% Interpreting social cues 100% Inability to pick up on social cues 100% Motivation to engage in social behavior 100% Repeating behaviors /obsessing over the routines 83% Social Impairment Ages (SRS-2) n=18 Interpreting social cues 100% Expressing social communication 100% Repeating behaviors /obsessing over routines 89% Inability to pick up on social cues 83% Motivation to engage in social behavior 50% Executive Functioning in Adults (BRIEF A) n=8 Remembering information in order to complete a task 50% Modulating emotional response 50% Least Move from one situation to another 25% Beginning tasks 25% Inhibiting behavior or not act on an impulse 25% Understand the effect of behaviors on others 25% Keeping work & living spaces orderly 25% Keeping track of problem solving successes or failures 25%
8 Distal18q with TCF4 deletion Main features of a TCF4 deletion TCF4 +/ (N=28) TCF4 +/+ (N=9) Average age Age range verbal No Yes Overall IQ 4 mo. (2 11mo) 54 (50 82) corpus callosum abn. 68% 0% hyperventilation 39% 33% Autism 71% 38% TCF4 Projects: Skin cells > ips cells > neurons Gene expression differences Drug testing Biomarker identification TCF4 +/ = people with 18q deletions that include the TCF4 gene. TCF4 +/+ = people with terminal deletions of 18q deletions close to but not including the TCF4 gene. Effects of growth hormone treatment Reanalysis of data from 2005 paper B Mental Age (Months) Change in mental age score of 3 children with TCF4 deletions before and after GH treatment Chronologic Age (Months) Effect of Childhood GH treatment in adults with 18q- Adults with 18q- who are: GH deficient Treated with GH from childhood Remained GH deficient BMI Height Cognitive flexibility Problem solving Frustration control
9 Distal 18q Reference Group Distal 18q Reference Group Medical and Developmental History n=14 Feature % Feature % Motor Developmental delay 100 Congenital heart abn. 54 Delayed myelination 100 Allergic rhinitis 50 Hypotonia 93 Sinusitis 50 Foot anomalies 86 Eczema 44 Atretic/stenotic ear canals 77 Intention tremors 42 Neonatal complications 77 Strabismus 38 Growth hormone deficiency 71 Pneumonia 36 Hearing loss 71 Scoliosis 33 Recurrent ear infections 69 IgA deficiency 33 Hypospadias (2/3 boys) 67 Umbilical hernia 33 Complication during pregnancy 67 Autoimmune disorders 31 Tapered fingers 64 Thyroid abnormality 31 Flat midface 60 Constipation 29 Proximal thumbs 57 Kidney malformations 25 Palate abnormality 57 Hyper flexibility of joints 21 Food/ drug allergies 56 Seizures 20 Gastro-esophageal reflux 56 Developmental Milestones = Average score = the full range of scores = the normal range Behavioral Measures IQ = normal IQ range = average IQ score = mild ID range = severe to profound = Average score = the full range of scores = normal range = at risk range = problem range
10 Distal 18q (all) Management Guide Potential conditions in a neonate Structural Hernias (inguinal, umbilical) Cryptorchidism, chordee, and hypospadias in >50% of males Palate abnormality Functional Respiratory and feeding difficulties Hypotonia Biochemical Jaundice Initial evaluations after diagnosis Cardiology evaluation 29% have cardiac defects Orthopedic exam 74% with foot defects Otolaryngology including audiology evaluation >50% with hearing loss Thyroid levels 15% with hypothyroidism Renal ultrasound 18% with reflux or malformations Ophthalmology exam 72% with optic problems Genitourinary Neurology / cerebral MRI evaluation Pediatric anesthesiology if surgery is indicated Referrals to Appropriate subspecialist as indicated by initial evaluations Genetics Follow up Parents genotyped for balanced rearrangements Early intervention/developmental services The Chromosome 18 Registry & Research Society The Chromosome 18 Clinical Research Center Closely monitor and manage Failure to thrive/ growth failure Weight gain Linear growth Sinus/ ear infections Genitourinary Reflux Immunology/Rheumatology IgA deficiency Atopic disorders Arthritis Other autoimmune conditions Neurology Seizure disorder Intention tremors Hypotonia Orthopedics Scoliosis or kyphosis Development Milestones School performance Behavioral/ mood changes Annual Screenings Thyroid Vision Hearing
11 Distal 18q (with deletion not including TCF4) 18q- Natural History 104 individuals age 18 and over Living Situation: Live with their parents/guardians 60 With parents in independent area 3 Spouse/partner 5 Independent 5 Supervised independent living program 3 Group Home / Host / Extended Family 8 With roommate 3 Dormitory 1 Unknown 16 Martial Status/Children: Never married 78 Married 4 2 No live births 1 One live birth 3 Three live births 1 No children 77 2 Work (Volunteer, Part-time, Full-time): Yes 48 No 36 0 Highest educational level: Did Not Complete High School 6 Attending High School 6 High School Graduate (certificate) 18 High School Graduate (diploma) 29 High School Graduate (unknown) 3 Attending College/University 9 Some Vocational School (no degree) 1 Some College/University (no degree) 6 Associate Degree 1 Bachelor Degree 2 Master Degree 1 Vocational School Degree/Certificate 5 Unknown 17 Behavior- Adults (BASC-2) n=70 Performing basic tasks safely 46% Avoiding social contact 46% Ability to work for a common goal 39% Expressing ideas in a way understood by others 30% Odd Behaviors 30% Least Nervous, fearful and worrisome tendencies 17% Anti-social and rule-breaking behaviors 11% Distractible unable to concentrate 10% Social Impairment - Adults (SRS-2) n=61 Interpreting social cues 70% Repeating behaviors /obsessing over the routines 67% Expressing social communication 62% Motivation to engage in social behavior 54% Inability to pick up on social cues 51% Social Impairment Ages (SRS-2) n=59 Repeating behaviors /obsessing over routines 81% Interpreting social cues 78% Expressing social communication 73% Inability to pick up on social cues 64% Motivation to engage in social behavior 56% Executive Functioning in Adults (BRIEF A) n=78 Keeping track of problem solving successes or failures 62% Move from one situation to another 56% Remembering information in order to complete a task 54% Managing current & future oriented tasks 54% Least Keeping work & living spaces orderly 29% Inhibiting behavior or not act on an impulse 28%
12 18q : Current Ages & Age at Death Proximal 8% Complex TCF4 +/ Distal 32% 35% 5% Proximal 18q Age in years Age deceased Gender Cause of death Past medical history 11 years 7 months M Seizure complications At 5 months parents report that he has never breathed normally; spastic cerebral palsy; dysphagia-g-tube; Nissen fundoplication; epilepsy; pneumonia several times/aspirating; obstructive apnea; allergic to mold, morphine and codeine; hiatal hernia Complex Rearrangements Age deceased Gender Cause of death Past medical history 15 months F N/A 2 years 6 months M 13 years 3 months M Heart complications after heart surgery N/A 16 yrs 3 months M Kidney and heart failure 23 years M Complications after bowel obstruction surgery. Multiple congenital heart defects; G-tube; hernia repair; intestine malrotations; hydrocephalus; pallor optic nerves; severe sleep apnea Multiple heart surgeries; malrotated bowel; hypothyroidism; reactive airway disease Central hypotonia; 2 yrs 4 months: hypertonia; bilateral hearing loss; severe developmental delay; renal reflux; feeding difficulties; G-tube; aspiration Profound developmental delay; sleep disorder; staring spells; mitral and aortic valve insufficiency; bilateral hypoplastic kidneys; chronic renal insufficiency Neonatal complications; ASD; tricuspid insufficiency ; pulmonary valve stenosis; pneumonia several times; seizures; kidney stone; tracheomalacia; significant pulmonary disease 31 years F N/A No medical records available 45 years F Choking due to a recurrent habit of retaining food in her cheeks No medical records available
13 Distal 18q, TCF4 +/ Age deceased 22 mo F 6 rs 10 mo M Gender Cause of death Past medical history Admitted to the Hospital for central apnea. Developed tachycardia Aspiration ( at the time of death had cold/congestion). Admitted to the Hospital for not breathing. Cause of death : aspiration 8 yr M Sepsis 13 yr M 13 yr 3 mo F Sepsis (developed an infection on his liver which was not able to to be controlled and spread to other organs) Very unexpectedly and suddenly. Fell ill what appeared a cold, got antibiotics, After two days, when mother went to check on her in the morning found her struggling to breath, Emergency help, but she passed away. Post mortem findings: Intussusception. 16 yr 3 mo F N/A Respiratory distress;central apnea; respiratory tract infections very often; silent aspirations; failure to thrive; oropharyngeal dysphagia Reactive airway disease; pneumonia; dehydration; diarrhea; ASD which was closed spontaneously Never walked, talked or sit; poor immune system; developed interstitial lung disease and asthma; apnea; obstructed bowels; aspiration secondary to GERD; ASD; seizures; corneal staphyloma (Right) Immature lung development as a newborn; cortical blindness; pneumonia very often; silent aspirations; central apnea Only few medical records available: often respiratory infections; hypoplastic corpus callosum; Bronchitis always turned into bronchial pneumonia', at about 3 x a year; one lung functions only at 10% due to scarred tissues from pneumonia; asthma 16 yr 5 mo M Sudden death 17 yr 8 mo M 20 yr 11 mo F Was taking a nap and did not wake up. The cause of death was considered "natural causes". Death certificate:" cardiac arrest". Vomiting; poor feeding tolerance; Worsening apneic episodes; Adynamic illeus 22 yr F N/A 31 yr 8 mo M N/A Pneumonia many times; history of asthma; glaucoma in the left eye; transplant surgery in the left eye Had fluid in his lungs at birth, and required O2 for 4 days; abnormal tone and meconium stained amniotic fluid; IUGR; hypospadias and chordee; no medical records available after 3 months of age Recurrent aspiration pneumonia; central apnea; Irregular breathing cycles; history of cyclical vomiting; GE reflux; constipation; malrotation of intestine; pulmonary stenosis Pneumonia in multiple times; asthma; alopecia totalis; fused kidneys; trouble with swallowing and controlling secretions Seizures; pyloric stenosis; salivary gland surgery; orchiectomy; has had 3 pancreatitis/vomiting attacks; nonverbal, on wheelchair Distal 18q, TCF4 +/+ Age deceased Gender Cause of death Past medical history 8 yr 4 m F N/A 9 yr 4 m M Pulmonary hemorrhage per grandmother 10 yr 3 mo F N/A 12 years 9 m M N/A Pneumonia newborn; PDA (patent ductus arteriosus); PFO (patent foramen ovale); failure to thrive; congenital hypothyroidism; cleft palate; bifid thumb; club feet; slightly alrotated right kidney; records only as an infant. Nonverbal; nonambulatory; G-J tube for severe GERD; severe encephalopathy; seizure disorder; severe hypertonicity; spastic quadriparesis idiopathic pulmonary hemosiderosis; frequent pneumonias; respiratory distress; sinus arrythmia; minimal mitral regurgitation; several hospitalizations for pulmonary bleeding Records only at a very young age (2 yrs old): neonate: periodic breathing; episodes of apnea; pyloric stenosis; cleft palate; silent aspirations; jejunostomy tube; oropharyngeal dysmotility History of heart murmur-resolved; pulmonary valve stenosis-resolved? ; 19 yr 9 mo M Sudden death dysarthria; MRI: Chiari I malformation 20 yr 3 mo F Deep vein thrombosis then pulmonary Acquired hypothyroidism; hearing loss; records available up to 13 yrs old. embolism? Actual report n/a Only few records available 20 yr 6 mo F N/A History of gastroenteritis; failure to thrive ( records available only as a toddler) 25 yr 6 mo F N/A Failure to thrive; bilateral aural atresia; cleft palate; significant developmental delay; records available only until 7 years old Meningitis at 9 months old; asthma at 12 yrs old and lasted for about 8 yrs; 31 yr6 mo F Sudden, unstoppable epileptic event mitral insufficiency; history of seizures as a young adult: onset at 5 yrs old; periventricular leukomalacia ( MRI) 49 yr 8 m F N/A Torticollis; probable scoliosis; tremors starting at the age of 4 years old, and getting worse over the years; hearing loss; cerebral atrophy (MRI)
14 18p 04/ p deletions 18p Critical Regions
15 18p (cen) Newborn Physical Findings (N=31) Neonatal complications 74% Feeding Difficulties 42% Respiratory Difficulties 29% Jaundice 29% Hypoglycemia 10% Muscle tone abnormalities 84% Hypotonia 71% Mix abnormal tone 13% Immediate Referral Early Childhood Developmental services (OT, PT, ST) - Developmental delay 100% Genetics evaluation and counseling - Parental chromosome analysis or FISH Ophthalmology evaluation Strabismus 2% Optic nerve abnormalities 13% Congenital cataracts 6% Refractive Errors 52% Astigmatism 29% Hyperopia 32% Myopia 13% Initial Physical evaluation for: Cardiac Abnormalities 29% Holoprosencephaly findings 13% Single central incisor 10% Septo-optic dysplasia 3% Pectus Excavatum 29% Hernia (Inguinal, hiatal, umbilical) 29% Monitor and Refer Seizures 16% Nystagmus 6% Kyphosis/ Scoliosis 19% Reflux 13% Consipation 32% Growth hormone deficiency 35% Panhypotitutarism 6% Thyroid abnormalities 16% Hearing loss 22% Recurrent ear infections 61% Findings reported in more than 25% of this population include: Muscle tone abnormalities 88% Transient neonatal complications 63% Chronic otitis media 56% Refractive errors 53% Findings on the holoprosencephaly spectrum 31% Constipation 31% Strabismus 31% Cardiac anomalies 25% Growth hormone deficiency 25% Other less common findings include seizures, scoliosis, pectus excavatum, ptosis, hearing loss, and thyroid abnormalities.
16 Deletion of entire short arm of 18p Behavior in 18p-(cen) Adults (BASC-2) n=15 : Poor social skills 40% Avoiding social contact 40% No problems identified: Overly active and acting without thinking Engaging in anti-social and rule-breaking behaviors Incapacitating sadness or stress Easily distractible and unable to concentrate Deletion of part of the short arm of 18p Behavior in 18p-(non-centromere) Adults (BASC-2) n=17 Common problems: Inability to adapt readily to changes 53% Inability to work with others for a common goal 50% Less common problems Nervous, fearful and worrisome tendencies 18% Easily distractible and unable to concentrate 12% Hostile and threatening behavior 6% Anti-social and rule-breaking behaviors 6% Executive Functioning in 18 p-(cen) Adults (BRIEF-A) n=16 : Moving from one situation to another 69% Keeping track problem solving successes/failures 50% No problems identified: Inability to inhibit, resist, or not act on an impulse Executive Functioning in 18 p-(noncentromere) Adults (BRIEF-A) n=16 Common problems: Tracking of problem solving successes/failures 75% Moving from one situation to another 75% Keeping work and living spaces orderly 63% Managing current and future oriented tasks 56% Remembering information to complete a task 56% Beginning a task or independently generate ideas 50% Modulating emotional response 50% Less common problems: The inability to inhibit, resist, or not act on impulse 19% Social Impairment in 18p- (cen) individuals Adults n=17 (SRS-2) Picking up on social cues 54% Repeating behaviors/ obsessing same routines 53% Expressing social communication 53% Less common problems: Interpreting social cues once they are picked up 47% Motivation to engage in social behavior 35% Social Impairment in 18p- (cen) individuals years n=14 (SRS-2) Common problems: Obsessing over the same routines and rituals 86% Interpreting social cues 79% Motivated to engage in social behavior 71% Social communication 71% Picking up on social cues 71% Social Impairment in 18p- (non-centromere) individuals Adults n=15 (SRS-2) Common problems: Repeating behaviors and obsessing over routines 67% Interpreting social cues 67% Picking up on social cues 60% Social communication 60% Motivation to engage in social behavior 60% Social Impairment in 18p- (non-centromere) individuals years n=18 (SRS-2) Common problems: Obsessing over the same routines and rituals 78% Pick up on social cues 72% Interpret social cues 67% Social communication 61% Less Motivation to engage in social behavior 44%
17 18p- Natural History (>18 years) n=27 n=27 Living Situation: 18p-cen 18p-non-cen Live with their parents With parent in independent area 0 2 Supervised independent living program 0 2 Apartment alone 3 3 Group home 1 0 Unknown 8 5 Highest educational level: Did Not Complete High School 1 2 Attending High School 3 2 High School Graduate (certificate) 6 2 High School Graduate (diploma) 6 5 Attending College/University 1 2 Some College/University (no degree) 0 3 Associates Degree 2 4 Vocational School Degree/Certificate 0 2 Unknown 8 5 Martial Status/Children: Married (no) Married (unknown) 8 5 Separated / Divorced 0 1 Children (none) Children (unknown) 8 5 Work (Volunteer, Part-time, Full-time): Yes No 6 8 Unknown 8 5 Deceased 18p : Current Ages & Age at Death Current Age in years Age deceased Gender Cause of death Past medical history 13 years F Brain bleed post cardiac surgery 22 years 4 months F Pneumonia complicated by lupus Goldenhar syndrome; severe GE reflux; complex congenital heart disease Lupus nephritis; hypothyroid; adrenocorticotropic hormone deficiency
18 18p (cen) continued = Average score = the full range of scores = the normal range = normal IQ range = average IQ score = mild ID range = severe to profound = Average score = the full range of scores = normal range = at risk range = problem range
19 Chromosome 18p Dosage Sensitive Genes (66 genes in total on 18p) 1 1,000,000 CETN1 SMCHD1 EMILIN2 TGIF DLGAP1 CETN1 = Male infertility Our data: None evaluated 0/22 adult males are fathers SMCHD1 = FSH Dystrophy 2 Digeneic DUX4 2 nd gene (small array, A allele) Age of onset before age 20 Progressive muscle weakness (asymmetric); shoulders upper arms, lower leg Our data: 0/21 affected (8-30 years old; ave. age 18) 2/83 genetically at risk EMILIN2 -?? Or any of 20 genes Our data: 11 18p- = poor platelet function & 8 Tet18p = normal platelet function TGIF = Holoprosencephaly Our data: 6/65 (single central incisor, iris coloboma, piuitary abn.) LAMA1 LCCR30 ANKRD12 LAMA1 = Tortuous Retinal Vasculature and keratosis pilaris Our data: 1/32 had retinal vascular anomalies 7/79 keratosis pilaris - from chart review (common in typical population) GNAL = Dystonia (Muscle Cramps) Age of onset 31.3 yrs. Range 7-54 years Common effects = neck 82%, speech 92% Our data: neuro exam = 0/17 evaluated met criteria medical records = 2/58 had dystonia 10,000,000 IMPA2 GNAL AFG3L2 PTPN2 AFG3L2 = Spinalcerebellar ataxia 28 Age of onset 24 years Range 3-60 years Likelihood of diagnosis = 93% Slowly progressive gait & limb ataxia - incoordination 100% Dysarthria- motor speech problem with articulation 100% Our data: :0/15 met criteria (8-30 years old; ave. age 16) PTPN2 - Inflammatory bowel disease (IBD) Mice with only 1 copy of PTPN2 have increased susceptibility to inflammatory bowel disease (IBD) Genetic Studies: Our data: Crohn s Disease & Ulcerative Colitis Rheumatoid arthritis Type 1 Diabetes?? 0/67 have IBD 11/67 had an autoimmune condition (juvenile rheumatoid arthritis, Sjogrens syndrome, hypothyroidism, graves, celiac, vitiligo, psoriasis, and alopecia) hg19 Centromere DLGAP1, LCCR30. ANKRD12, IMPA2 = implicated in autism Our data: 8/56 clinically significant GARS scores
04/ p. 18p deletions. 18p Critical Regions
18p 04/2017 18p deletions 18p Critical Regions 18p (cen) Newborn Physical Findings (N=31) Neonatal complications 74% Feeding Difficulties 42% Respiratory Difficulties 29% Jaundice 29% Hypoglycemia 10%
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