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Normal B-Cell (CD19+) Count Impaired Ig Class Switch Recombination IgG and IgA Low Major Fluid Shifts May Occur in Severe Cases Ovaries Return to Normal Size after Delivery Enlarged Multilocular Ovaries Zinc Deficiency in Breastfed Offspring Resolves after Weaning Breastfed Offspring Have Transient Decrease of Plasma Zinc Levels Breast Milk Zinc Decreased Balanced Translocation T-12-22: p11.2 - q13.3 Translocation Disrupting the FBLN1 Gene Metatarsal Synostosis (3rd and 4th Digits) Syndactyly (2nd, 3rd and 4th Digits) Bilateral, Symmetric Malformations Metacarpal Synostosis (4th and 5th Digits) Synpolydactyly (3rd or 4th Digits) Syndactyly (often 3rd and 4th Digits) Recurrent Bacterial Infections Beginning in Childhood No Opportunistic Infections Mean Age at Diagnosis Is 8.8 Years Low to Absent IgG IgA IgE Occurs Most Often in Developing Countries in Tropical Regions Median Age at Onset Is 21 Years Mutation in the SPINK1 Gene Increased Risk of Pancreatic Cancer Intraductal Calculi Especially in the Caput Recurrent Abdominal Pain Since Childhood Insulin-Dependent but Ketosis-Resistant Diabetes Incidence of Fibrocalculous Pancreatic Diabetes Increased No Neurologic Sequelae Seizures Usually Remit Spontaneously by 12 Months of Age Compression Deformities of the Spine Prominent Widely-Spaced Incisors Rapid-Onset Cataracts Peripheral Hypertonia Usually Clinically Asymptomatic Nerve Biopsy May Show Demyelination and Remyelination Non-Progressive Deafness Profound Sensorineural Prelingual Deafness Cognitive Deficits May Occur Delayed Development May Occur No History of Familial Hypercholesterolemia No Childhood Hypertension ECG Pattern Consistent With Acute MI Chest Pain Lasts More than 30 Minutes >70% Stenosis (Coronary Angiogram) History of Coronary Artery Bypass Grafting History of Percutaneous Transluminal Coronary Angioplasty No Congenital Heart Defect No Insulin Dependent Diabetes Mellitus Begins in Feet and Legs Possibly Foot Deformities No Onion Bulb Formations Nerve Fiber Density and Thickness Decreased Axonal Regeneration on Nerve Biopsy Low to Normal Range of Nerve Conduction Velocity Cardiac Anomalies (13%) Thick Skin (74%) Microspherophakia (74%) Muscular Build Adult Female Height 130-157cm Adult Male Height 142 - 169 cm Onset in Early Childhood, 2-4 Years Occasional Early 'Onion' Bulb Formations Thin Myelination Regenerating Axons Nerve Conduction Velocities Vary from Normal to Decreased EMG Shows Neuropathic Changes Clumsy Gait Normal Early Motor Milestones Intrafamilial Phenotypic Variation May Occur Visual Acuity Is Normal Nystagmus Decreases on Convergence Frequency 6 Hz In Lateral Gaze Frequency 3.5 Hz in Midline Small Rotary Component May be Present Jerky, Horizontal, Congenital Nystagmus Non-Progressive and More Severe Progressive Forms Clinical Variability Onset Ranges from Childhood to Adulthood No Hypertrophic Cardiomyopathy Vital Capacity Due to Muscle Weakness Reduced Positive for ATPase Activity at pH=4.3 Type 1 Fibers with Inclusions Containing MYH7 Protein Aggregates Subsarcolemmal Hyaline Bodies in Type 1 Fibers Only Muscle Biopsy Shows Type 1 Fiber Predominance EMG Shows Myopathy Generalized Proximal and Distal Muscle Weakness Scapuloperoneal Amyotrophy Neurogenic Scapuloperoneal Syndrome Caused by Mutation in the Aggrecan 1 Gene Progressive Osteoarthropathy (Early Onset) Sclerotic Vertebral Bodies End-Plate Irregularities Anterior Osteophytes Stocky Body Habitus Proportionate Short Stature (<5th Percentile) Multiple Retinal Holes Ocular Axial Length Increased Bilateral High Grade Myopia