To Be Your Local Expert A General Pediatrician s Story

Transcription

1 To Be Your Local Expert A General Pediatrician s Story DDC Clinic mission: To enhance the quality of life for people with special needs caused by rare genetic disorders

2 What Does It Take to Be Your Local Expert?

3 Through My Window

4 - Research Clinic Opens in Ohio for Genetic Maladies That Haunt Amish Families By FRANCIS X. CLINES June 20, 2002

5 You Have a Lot to Learn! Chicken breast disease Amish Normaline myopathy Autosomal recessive Onset with neonatal tremors and hypotonia Contractures Chest deformity Respiratory failure

6 To be your local expert is not simply a desire or a choice, it is a call of duty!

7 Cohen Syndrome Overview Genetics: autosomal recessive First reported by Dr. Michael Cohen in 1968 Gene related to the disease: COH1 (VPS13B) on chromosome 8q22 Incidence: Over 1000 patients are diagnosed worldwide, and over 200 patients are reported A disease with multiple system involvements

8 7 th Cohen Syndrome Family Gathering in June 2014

9 Cohen Syndrome Clinical Manifestations Psychomotor retardation Microcephaly Characteristic facial features Childhood hypotonia and joint laxity Progressive retinochoroidal dystrophy and myopia Truncal obesity Neutropenia Cheerful disposition Any earlier signs or symptoms?

10 Cohen Syndrome Fetal Movements in 65 Patients

11 Cohen Syndrome Facial Features Thick hair and low hairline High-arched and waved-shaped eyelids Long and thick eyelashes, thick eyebrows High and narrow palate Short philtrum and prominent upper central incisors, resulting in open-mouth appearance

12 Cartilage-hair Hypoplasia Dwarfism (CHH) First reported in 1965 by McKusick et al Genetics: autosomal recessive Related gene: ribonuclease mitochondrial RNA-processing (RMRP) gene Common clinical features Short stature Metaphyseal dysplasia Fine sparse hair Hirschsprung disease Immunodeficiency Hematologic malignancies A huge phenotypic variation

13 Amish Brittle Hair Syndrome First described in early 1970s The disease related gene identified on 2005: TTDN1 or C7ORF11 on chromosome 7p14 Genetics: autosomal recessive Other names: nonphotosensitive trichothiodystrophy, hair-brain syndrome, BIDS syndrome Clinical features (brittle hair, intellectual impairment, decreased fertility and short stature)

14 Cockayne Syndrome Genetics: autosomal recessive Related genes: ERCC6 and ERCC8 Severe in Amish, notable at birth Severe microcephaly, failure to thrive photosensitivity, congenital cataracts and sensorineural hearing loss

15 MOPD (Microcephalic Osteodysplastic Primordial Dwarfism) Type I He et al. Science 2011;332: Microcephalic osteodysplastic primordial dwarfism type 1 Published by AAAS

16 TMCO1 Defect Syndrome Autosomal recessive disorder Characterized by distinctive craniofacial dysmorphism, skeletal anomalies, mental retardation and frequent sinus infections TMCO1 defect syndrome is proposed as name of the disease Xin B et al. PNAS 2010;107: by National Academy of Sciences

17 SAMS Association Another novel condition we described recently An acronym (first 3 letters of gene SAMHD1 as well) is used to name the disease Stenosis Aneurysm Moyamoya Stroke Synonym: Aicardi Goutières syndrome (AGS) The gene may be associated with stroke Xin B et al. PNAS 2011;108: by National Academy of Sciences

18 Prenatal Findings and Newborn Screening Fetal movement: less active in Cohen syndrome and TMCO1 defect syndrome Umbilical cord: thinner in SAMS association Birth weight SAMS association low end of normal Cockayne syndrome even smaller MOPD type I very small, often less than 3 lb Newborn hearing screening Often fail Cockayne syndrome and GM3 deficiency

19 How Does the Baby Cry? Cohen syndrome high-pitched, weak cry, like kitten NBIA (Hallervorden-Spatz disease or syndrome) like laughing SIDDT (sudden infant death with dysgenesis of the testes) syndrome - an unusual staccato cry, like a goat Cockayne syndrome quiet cry, seldom cry GM3 synthase deficiency cried his/her head off

20 Don t Forget to Challenge Your Authorities! History or diagnosis History of meningitis Suspect SAMS association Early onset of stroke A severely irritable baby, febrile or afebrile, a sepsis work-up negative Cui-du-chat syndrome Rett syndrome Autism GM3 synthase deficiency Cohen syndrome Misdiagnosed? Misdiagnosed?

21 Learn Some Pennsylvania Dutch It Can t Hurt! Look at ears - Hold still Open your mouth, bigger! Bilingualism delays onset of dementia (4.5 years) (Alladi et al, Neurology 81:1938, 2013)

22 What is Genetics?

23 Final Thoughts These special children are not just interesting medical problems, subjects of grants, and research. Nor should they be called burdens to their families and communities. They are children who need our help and, if we allow them to, they will teach us compassion, they will teach us to love. If we come to know these children as we should, they will make us better scientists, better physicians, and thoughtful people Dr. Holmes Morton