Total Topics :40

Alport’s Sd (most cases): "hereditary nephritis", type IV collagen deficit, mutation of COL4A5 ("colaas" - alpha-5 chain, type 4 collagen), hearing loss, ocular abnormalities (lens & cornea), hematuria since childhood (gross, micro)

Charcot Marie Tooth: loss of motor & sensory innervation, distal weakness & sensory loss, wasting in the legs, decreased deep tendon reflexes, tremor, foot deformity with a high arch is common (pes cavus), legs look like inverted champagne bottles. Most accurate test: electromyography. No tx.

Focal Dermal Hypoplasia: skin abnormalities and a wide variety of defects in eyes; teeth; and skeletal, urinary, gastrointestinal, cardiovascular, and central nervous systems.

Fragile X Syndrome: CGG trinucleotid repeat, FMR 1 gene mutation, mental retardation, large ears and jaw, post-pubertal macro-orchidism (males), attention deficit disorder (females)

Hypophosphatemic rickets: infants may show growth retardation, widened joint spaces and flaring at the knees at age 1 (> boys), bowing of the weight-bearing long bones, young children-dentition absent or delayed, older children-multiple dental abscesses.

Incontinentia pigmenti: skin abnormalities (blister--> warts--> hyperpigmentation--> hypopigmentation), alopecia, hypodontia, cerebral atrophy, slow motor development, mental retardation, seizures, skeletal & structural anomalies. Letal >males.

Orofaciodigital Sd: OFD1 gene mutation, malformations of face, oral cavity, digits with polycystic kidney disease and variable involvement of the central nervous system.

RETT’s Sd: sporadic mutation of MECP2 gene, onset 2yo, acquired microcephaly, stopped development, motor & speech regression, autism-like behavior, self-mutilating behavior, inconsolable crying/screaming fits, emotional inversion, hypotonia, dystonia, chorea, bruxism, scholiosis, long QT

Thalassemia

Thalassemias are a heterogeneous group of hereditary blood disorders characterized by faulty globin chain synthesis resulting in defective hemoglobin, which can lead to anemia

Thalassemia provides partial resistance against malaria.

Beta thalassemia

Clinical features

Minor variant (heterozygous): unremarkable symptoms (low risk of hemolysis, rarely splenomegaly)

Major variant (homozygous) Severe hemolytic anemia, Hepatosplenomegaly ,Growth retardation ,Skeletal deformities (high forehead, prominent zygomatic bones, and maxilla)

Alpha thalassemia

most commonly seen in people of Asian and African descent

Clinical features

Silent carrier: asymptomatic

Alpha thalassemia trait: mild hemolytic anemia with normal RBC and RDW

Hemoglobin H disease

Jaundice and anemia at birth

Chronic hemolytic anemia which may require transfusions

Hb-Bart's hydrops fetalis syndrome (most severe variant of alpha thalassemia)

Intrauterine ascites and hydrops fetalis, severe hepatosplenomegaly, and often cardiac and skeletal anomalies

Incompatible with life (death in utero or shortly after birth)

Diagnostics

Microcytic hypochromic anemia

Blood smear: target cells , teardrop cells

Bone marrow biopsy: reactive hyperplasia

Confirmatory tests

Hb-electrophoresis Alpha thalassemia can usually only be detected if ≥ 3 alleles are defective.

DNA analysis: to test for alpha thalassemia minor and minima (< 3 alleles defective)

Skeletal deformities -high forehead, prominent zygomatic bones and maxilla can be seen on all imaging modalities.

X-ray: hair-on-end (“crew cut”) sign