Differential diagnosis — Flashcards

Flashcard 31: Inheritance and genetic defect in Myotonic Dystrophy Type 1?

Answer: Autosomal Dominant (AD), CTG repeat in DMPK gene

Extra: Myotonic Dystrophy (Type 1): - Inheritance: AD - Genetics: CTG triplet repeat expansion in the DMPK gene (Chromosome 19). - Features: Myotonia (difficulty relaxing grip), muscle wasting, cataracts, testicular atrophy, frontal balding, and arrhythmia. - Mnemonic for CTG: Cataracts, Toupee (balding), Gonadal atrophy.

Flashcard 32: What is the developmental defect in holoprosencephaly?

Answer: Failure of the right and left cerebral hemispheres to separate, often due to mutations in the Sonic Hedgehog signaling pathway.

Extra: Manifests as a spectrum of midline defects ranging from cleft lip/palate to cyclopia. Associated with Trisomy 13 (Patau syndrome) and maternal diabetes.

Flashcard 33: What is the enzyme deficiency in Metachromatic Leukodystrophy?

Answer: Arylsulfatase A deficiency caused by accumulation of cerebroside sulfate.

Extra: Inheritance: Autosomal Recessive (AR) Clinical: Central and peripheral demyelination, ataxia, and dementia. Pathophysiology: Accumulation of sulfatides (cerebroside sulfate).

Flashcard 34: What test is used to differentiate the causes of B12 (cobalamin) deficiency?

Answer: Schilling test (administration of B12 and IF)

Flashcard 35: Clinical features and laboratory findings of Hereditary Spherocytosis?

Answer: Hemolytic anemia with increased MCHC, splenomegaly, and osmotic fragility. Cured by splenectomy.

Extra: Inheritance: Autosomal Dominant (most common). Defect: Spectrin, Ankyrin, or Band 3. Laboratory: High MCHC (pathognomonic), Spherocytes on peripheral smear. Treatment: Splenectomy removes the site of hemolysis but the RBC membrane defect persists.

Flashcard 36: What are the clinical features of 22q11 deletion syndrome?

Answer: CATCH-22: C - Cardiac defects (e.g., Tetralogy of Fallot) A - Abnormal facies T - Thymic aplasia (T-cell deficiency) C - Cleft palate H - Hypocalcemia (Parathyroid aplasia) 22 - 22q11 microdeletion

Extra: Due to aberrant development of the 3rd and 4th branchial pouches. Includes DiGeorge syndrome (primarily thymic/parathyroid/cardiac issues) and Velocardiofacial syndrome (primarily palate/facial/cardiac issues).

Flashcard 37: What manifestations of 22q11 deletion syndrome define DiGeorge syndrome?

Answer: cardiac, thymic, parathyroid defects

Flashcard 38: What are the key genetic and neurochemical findings in Huntington's disease?

Answer: CAG triplet repeat (Caudate Atrophy, GABA/ACh decrease) on Chromosome 4.

Extra: Clinical features: Chorea, athetosis, aggression, depression, progressive dementia. Pathophysiology: Neuron death via NMDA receptor-mediated glutamate toxicity. Gross findings: Atrophy of caudate and putamen (striatum), ex vacuo ventriculomegaly. Neurotransmitters: Decreased GABA and ACh; Increased Dopamine. Genetics: Autosomal Dominant, CAG repeats in HTT gene. Mnemonic: Hunting 4 Food (Chromosome 4, CAG = Caudate, ACh, GABA).

Flashcard 39: Key clinical features and inheritance of Marfan's syndrome?

Answer: Autosomal dominant connective tissue disorder caused by FBN1 mutation (fibrillin-1). Features: tall stature, arachnodactyly, ectopia lentis (upward), and aortic root dilation/dissection.

Extra: Clinical features: tall stature, long limbs, pectus excavatum, hypermobile joints, arachnodactyly, aortic incompetence or dissection, cystic medial necrosis of aorta, subluxation of ocular lens (upward/superotemporal). Inheritance: Autosomal Dominant (AD). Gene: FBN1.

Flashcard 40: Clinical features of Neurofibromatosis type 1 (von Recklinghausen's disease):

Answer: Cafe-au-lait spots, Lisch nodules (pigmented iris hamartoma), neurofibromas, optic pathway glioma, pheochromocytomas, skeletal abnormalities (e.g., sphenoid dysplasia).

Extra: Genetics: Autosomal Dominant, NF1 gene on chromosome 17. NF1 codes for neurofibromin (a negative regulator of Ras).