Understanding and Expanding the Phenotype in Norrie Disease
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Heidi L. Rehm, PhD, FACMG Heidi L. Rehm, PhD, FACMG Assistant Professor of Pathology, BWH and HMS Clinical Molecular Geneticist, Laboratory for Molecular Medicine, PCPGM Understanding and Expanding the Phenotype in Norrie Disease
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Dr. Heidi Rehm discusses the effects of Norrie Disease on the eyes, ears, brain, and vascular system. (NDA International Conference, 2009)
Transcript of Understanding and Expanding the Phenotype in Norrie Disease
Heidi L. Rehm, PhD, FACMGHeidi L. Rehm, PhD, FACMGAssistant Professor of Pathology, BWH and HMS
Clinical Molecular Geneticist, Laboratory for Molecular Medicine, PCPGM
Understanding and Expanding the Phenotype in Norrie Disease
Norrie Disease Pedigree from Costa Rica
Venous Insufficiency in the Costa Rican Norrie Disease Kindred
Other Eye Disorders due to Norrie Disease Gene Mutations
Familial exudative vitreoretinopathy (XL)
peripheral retinal avascularity → exudation and retinal detachment
Coats’ disease
retinal telangiectasia (dilated and tortuous vessels) → exudation and retinal detachment
Loss of Fine Capillary Network in the Norrie Disease Retina
Control
NorrieDisease
Central Peripheral
Outer Retina
Inner Retina
Nor
rie D
isea
seC
ontr
ol
Missing Outer Vasculature in the Norrie Disease Retina
Inner Outer
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Hair Cell Stimulation
Sound wave
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Hair Cell Transduction
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Metabolic Recycling in the Cochlea
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Endolymph
NDP Gene Expression in Inner Ear
Zheng-Yi Chen
Hearing Loss in the Norrie Mouse Model
Norrie Mouse Inner Ear Pathology
Control Knockout
3 m
onth
15 m
onth
Capillaries of the Cochlear Stria Vascularis
Vascular Changes in the Norrie Mouse Cochlea
Norrie DiseaseControl15 months
Vascular Changes in the Norrie Mouse Cochlea
Norrie DiseaseControl3 months
Changes in the Norrie Mouse Stria Vascularis
3 months
Summary
One of the primary defects in Norrie disease may be dysfunction of the cells that interact with blood vessels.
Norrin may also have a broader role in vascular biology.
Norrie Disease Clinical Survey Study
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0-3 4-10 11-20 21-30 31-40 41-50 51-60 60+
Num
ber
of P
art
icip
ant
s
Age Range (years)
56 individuals with Norrie disease participated in our survey
Participants Reporting Peripheral Vascular Disease
Peripheral vascular disease (PVD), including varicose veins, leg ulcers, and/or erectile dysfunction, was reported in 21/56 (38%) of all participants or 21/36 (58%) of those 16 or older.
Erectile Dysfunction in Norrie Disease
Of the 24 men queried 14/24 (58%) reported erectile dysfunction. Three men had decreased penile blood flow documented by angiography and Doppler ultrasound. Two had successful penile implants.
Neurological Phenotype in Norrie Disease
2%1/51 Mood Disorders
25%13/51 Labile Affect
6%3/51 Anxiety
8%4/51 Attention Difficulties
27%14/51 Autism/Autistic-like
45%23/51Behavior Disturbance
28%14/51Cognitive Impairment
9%5/56 Chronic Seizures
7%4/56 Resolved Seizures
16%9/56Seizure Disorder
PercentageN/Total
Participants Reporting Hearing Loss
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0-3 4-10 11-20 21-30 31-40 41-50 51-60 60+
Registered
HL
Age Range (years)
Nu
mb
er o
f Par
ticip
ants
The average age of hearing loss was 12 yrs. With one exception, all individuals 25 and older had developed hearing loss and the earliest age of onset was 5 yrs.
Acknowledgments
Kathie SimsSharon Smith
David Corey Duan-Sun ZhangZheng-Yi Chen
Max Planck Institut Wolfgang Berger
MEEIChris BrownBarbara BurgessJoe AdamsChris Halpin
Cynthia Morton
