Snapshot A 10-year-old boy is brought to the pediatric endocrinologist due to short stature. The mother reports that her son is not as tall as his classmates, and this is causing him stress. On physical exam, there is macrocephaly with frontal bossing, shortening of the arms and legs, and lumbar lordosis. Arrangements are made for genetic molecular testing. Introduction Clinical definition a congenital skeletal dysplasia that results in shortened extremities and macrocephaly also known as dwarfism Etiology autosomal dominant gain-of-function mutation in fibroblast growth factor receptor (FGFR3) Pathogenesis constitutively active FGFR3 activity impairs chondrocyte proliferation and differentiation this in turn leads to impaired long bone formation (via endochondrial ossification) enlarged head relative to limbs (via membranous ossification) Associated findings most common cause of dwarfism normal life span, intelligence, and reproduction Presentation Symptoms asymptomatic Physical exam macrocephaly frontal bossing shortening of arms and legs proximal/rhizomelic segments are more notable lumbar lordosis kyphoscholiosis Treatment Conservative monitoring, preventing, and addressing complications e.g., leg bowing is managed with physical therapy
QUESTIONS 1 of 3 1 2 3 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI Blood, Plasma, Serum Reference Range ALT 8-20 U/L Amylase, serum 25-125 U/L AST 8-20 U/L Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL Calcium, serum (Ca2+) 8.4-10.2 mg/dL Cholesterol, serum Rec: < 200 mg/dL Cortisol, serum 0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h Creatine kinase, serum Male: 25-90 U/LFemale: 10-70 U/L Creatinine, serum 0.6-1.2 mg/dL Electrolytes, serum Sodium (Na+) 136-145 mEq/L Chloride (Cl-) 95-105 mEq/L Potassium (K+) 3.5-5.0 mEq/L Bicarbonate (HCO3-) 22-28 mEq/L Magnesium (Mg2+) 1.5-2.0 mEq/L Estriol, total, serum (in pregnancy) 24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL Ferritin, serum Male: 15-200 ng/mLFemale: 12-150 ng/mL Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250 pH 7.35-7.45 PCO2 33-45 mmHg PO2 75-105 mmHg Glucose, serum Fasting: 70-110 mg/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative stimuli: > 7ng/mL Immunoglobulins, serum IgA 76-390 mg/dL IgE 0-380 IU/mL IgG 650-1500 mg/dL IgM 40-345 mg/dL Iron 50-170 μg/dL Lactate dehydrogenase, serum 45-90 U/L Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL Osmolality, serum 275-295 mOsmol/kd H2O Parathyroid hormone, serume, N-terminal 230-630 pg/mL Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L Phosphorus (inorganic), serum 3.0-4.5 mg/dL Prolactin, serum (hPRL) < 20 ng/mL Proteins, serum Total (recumbent) 6.0-7.8 g/dL Albumin 3.5-5.5 g/dL Globulin 2.3-3.5 g/dL Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h Thyroxine (T4), serum 5-12 μg/dL Triglycerides, serum 35-160 mg/dL Triiodothyronine (T3), serum (RIA) 115-190 ng/dL Triiodothyronine (T3) resin uptake 25%-35% Urea nitrogen, serum 7-18 mg/dL Uric acid, serum 3.0-8.2 mg/dL Hematologic Reference Range Bleeding time 2-7 minutes Erythrocyte count Male: 4.3-5.9 million/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 12.0-16.0 g/dL Hemoglobin, plasma 1-4 mg/dL Leukocyte count and differential Leukocyte count 4,500-11,000/mm3 Segmented neutrophils 54%-62% Bands 3%-5% Eosinophils 1%-3% Basophils 0%-0.75% Lymphocytes 25%-33% Monocytes 3%-7% Mean corpuscular hemoglobin 25.4-34.6 pg/cell Mean corpuscular hemoglobin concentration 31%-36% Hb/cell Mean corpuscular volume 80-100 μm3 Partial thromboplastin time (activated) 25-40 seconds Platelet count 150,000-400,000/mm3 Prothrombin time 11-15 seconds Reticulocyte count 0.5%-1.5% of red cells Thrombin time < 2 seconds deviation from control Volume Plasma Male: 25-43 mL/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 19-31 mL/kg Cerebrospinal Fluid Reference Range Cell count 0-5/mm3 Chloride 118-132 mEq/L Gamma globulin 3%-12% total proteins Glucose 40-70 mg/dL Pressure 70-180 mm H2O Proteins, total < 40 mg/dL Sweat Reference Range Chloride 0-35 mmol/L Urine Calcium 100-300 mg/24 h Chloride Varies with intake Creatinine clearance Male: 97-137 mL/minFemale: 88-128 mL/min Estriol, total (in pregnancy) 30 wks 6-18 mg/24 h 35 wks 9-28 mg/24 h 40 wks 13-42 mg/24 h 17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 6-15 mg/24 h Osmolality 50-1400 mOsmol/kg H2O Oxalate 8-40 μg/mL Potassium Varies with diet Proteins, total < 150 mg/24 h Sodium Varies with diet Uric acid Varies with diet Body Mass Index (BMI) Adult: 19-25 kg/m2 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + (M1.MK.72) A young boy presents to your office for evaluation. He is not growing as quickly as his twin brother (Figure A). Genetic testing reveals a mutation in the fibroblast growth factor receptor gene.What is the most likely mode of inheritance? Review Topic QID: 106538 FIGURES: A 1 Autosomal dominant 78% (75/96) 2 Autosomal recessive 14% (13/96) 3 X-linked recessive 4% (4/96) 4 X-linked dominant 2% (2/96) 5 Mitochondrial 1% (1/96) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 (M1.MK.4722) A 3-year-old male is brought in to his pediatrician by his mother because she is concerned that he is not growing appropriately. Physical examination is notable for frontal bossing and shortened upper and lower extremities. His axial skeleton appears normal. He is at the 7th percentile for height and 95th percentile for head circumference. He demonstrates normal intelligence and is able to speak in three-word sentences. He first sat up without support at twelve months and started walking at 24 months. Genetic analysis reveals an activating mutation in a growth factor receptor. Which of the following physiologic processes is most likely disrupted in this patient’s condition? Review Topic QID: 108535 1 Intramembranous ossification 12% (32/273) 2 Osteoblast maturation 10% (27/273) 3 Endochondral ossification 62% (170/273) 4 Production of type I collagen 10% (27/273) 5 Bone resorption 3% (9/273) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 (M1.MK.27) A 9-month-old female infant is brought in by her mother to the pediatrician because she is concerned that her daughter is not growing normally. On physical exam, the head circumference is 95th percentile and the height is 5th percentile. The child has disproportionate growth such that both the upper and lower extremities show a rhizomelic pattern of shortening, but the axial skeleton appears to be normal. The child appears to have normal intelligence, but has delayed motor milestones; specifically, she is not able to roll or sit up by herself. Which of the following best describes the mode of inheritance for this disorder? Review Topic QID: 107010 1 Autosomal recessive 17% (19/110) 2 Autosomal dominant 62% (68/110) 3 X-linked recessive 5% (6/110) 4 X-linked dominant 4% (4/110) 5 Mitochondrial pattern of inheritance 9% (10/110) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2