Genetic disorders (Condensed) - 2026

Gene affected in Marfan syndrome, which is an autosomal dominant condition

Fibrillin-1 gene in Chromosome 15 - This condition is associated with skeletal abnormalities as its most striking features

Pattern of lens subluxation in Marfan syndrome

Outward and upward

Most life-threatening feature of Marfan syndrome

Cardiovascular abnormalities (e.g. mitral valve prolapse, aortic dissection, and aortic root dilation).

Pattern of lens subluxation in homocystinuria

Inward and downward

Characteristic manifestation of Tay Sachs disease and Niemann Pick disease in the retina

Cherry red spot in the macula - Both Tay-Sachs and Niemann Pick disease have cherry red spots, but only Niemann Pick disease has visceral involvement (e.g. hepatomegaly)

Characteristic engorged secondary lysosomes resembling concentric lamellated myelin figures seen in Niemann Pick disease in EM

Zebra bodies

Most common form of hypogonadotropic hypogonadism; Autosomal and X-linked disorder characterized by failure of olfactory axons and GnRH expressing neurons to migrate from the olfactory placode to the brain

Kallmann syndrome. Males: Micropenis, delayed puberty; Females: Primary amenorrhea, failure of secondary sexual development

Defining feature of Kallmann syndrome

Anosmia

Type of error of gametogenesis with failure of homologous chromosomes or sister chromatids to separate during cell division; most common cause of Trisomy 21

Nondisjunction - This leads to one gamete having an extra chromosome; the other gamete lacks one.

Most common of the chromosomal disorders and the leading cause of mental retardation; (+) simian crease (single palmar crease); (+) Brushfield spots

Trisomy 21

Responsible for most deaths in infancy and early childhood in Trisomy 21

Cardiovascular disease - (e.g. atrioventricular septal defects, ventricular/atrial septal defects, TOF)

Neurodegenerative condition associated with Trisomy 21

Early onset Alzheimer disease - Remember that amyloid precursor protein is found in chromosome 21.

Common musculoskeletal features of trisomy 13 and 18

Rocker bottom feet - Other distinguishing features of Patau and Edward syndrome are cleft lip and palate and umbilical hernias.

Most common karyotype associated with Klinefelter syndrome

47XXY - This condition is associated with hypogonadism and a eunuchoid body habitus.

Single most important cause of primary amenorrhea, associated with short stature, absence of secondary sex characteristics, (+) 45XO karyotype

Turner syndrome

Most important cause of increased mortality in Turner syndrome

Cardiovascular disease (e.g. preductal coarctation of the aorta, bicuspid aortic valve, aortic root dilation/dissection)

Feature of trinucleotide repeat disorders, where there is worsening of the disease with each successive generation

Anticipation

2nd most common cause of mental retardation after Trisomy 21; Trinucleotide repeat expansion disorder associated with long face, large mandible, large, everted ears, and macro-orchidism, and marked intellectual disability

Fragile X syndrome

Trinucleotide repeat expansion seen in Fragile X syndrome

CGG expansion in FMR1 gene (X chromosome)

Neurodegenerative disorder affecting the cortical and striatal neurons, causing dementia and choreoathetosis

Huntington disease

Defect in Huntington disease

CAG expansion on HTT gene (chromosome 4)

Disorder of genomic imprinting due to deletion in paternally derived Chromosome 15; associated with obesity, hyperphagia, and hypogonadism

Prader Willi syndrome

Disorder of genomic imprinting due to deletion in maternally derived Chromosome 15; associated with inappropriate "happy puppet" laughter

Angelman syndrome