Chromosomal Disorders MCQs

Wolf Hirschhorn syndrome. Also known as 4p- (deletion of4pl6), this syndrome is characterized by microcephaly and unusual development of the nose and orbits that produces an appearance suggesting an ancient Greek warrior's helmet. Other anomalies commonly seen include cleft lip and palate and cardiac and renal defects. Seizure disorders are common, and the majority of patients have severe intellectual disability. Reference: CDT Pediatrics 2020/Page 1097

Cleft lip/palate shows polygenic/multifactorial inheritance. Fragile X syndrome and G6PD deficiency show X linked recessive, whereas Cystic fibrosis shows Autosomal recessive inheritance. Reference: Nelson 21 st Ed/Chapter 97

The findings of large head, large ears, large jaw and large testes (macro-orchidism) are suggestive of Fragile X Syndrome. More commonly seen in boys, it is considered to be a trinucleotide repeat disorder Involves >200 CGG repeats in FMR-1 gene on Chromosome Xq27.3 Other features include hyperextensible joints, increased risks of ADHD, Autism, Anxiety Disorders Most patients have low IQ, indicating intellectual disability and delayed development milestones during childhood. Reference: Nelson 21 st Ed, Chapter 98.5

Childhood acute leukemias can be divided into myelocytic and lymphocytic. Acute myelocytic leukemias (AML) involve greater than 20% of myeloid blasts in either of these. Myeloid lines include erythrocytes, granulocytes, monocytes, and megakaryocytes. Acute lymphocytic leukemia (ALL) involves the B and T cell lymphocyte lineage. There are different chromosomal rearrangements that can occur, including translocations, deletions, and inversions. Chromosomal translocation (15;17) has a specific association with acute promyelocytic leukemia (APL). This translocation involves the alpha retinoic acid receptor gene on chromosome 17, which is why the specific treatment for APL is all-trans retinoic acid. Reference: Nelson textbook of Pediatrics, 20 th edition, pg. 2442

Upto 10% of Down Syndrome patients can develop Transient leukemia, previously called as Transient Myeloproliferative Disorder. Those developing Transient Leukemia in such patients are often found to have GATA-1 mutations in the transcription factors, producing proliferation of blast cells. 20-30% of these patients tend to develop AML-M7 leukemia by 3 years of age. Reference: Nelson 20 th Ed, Page 609, OP Ghai 10 th Ed, Page 667.

One-liners to remember regarding intellectual disability or mental retardation MC genetic cause: Down syndrome MC inherited cause: Fragile X syndrome MC preventable cause: Hypothyroidism MC treatable cause: Hypothyroidism Variable degree in the same family: Tuberous Sclerosis Mild MR in male with aneuploidy: Klinefelter Syndrome Reference: OP Ghai 9 th Edition, Various Pubmed Articles

Down syndrome has higher incidence of leukemia among the options. The most common is Acute Lymphoblastic Leukemia The most specific sub type of AML is M7. Tags : Topic : DOWNS SYNDROME Difficulty level : GOOD TO KNOW PYQ : FMGE JULY 2023 Reference : Nelson textbook of pediatrics, 21 st ed., pg. 660

As per OP Ghai 10th Edition, the chief cause of early mortality in Down Syndrome patients is Congenital Heart Disease. Furthermore, Endocardial Cushion Defects (ECDs) are the most common congenital heart disease in patients with Down Syndrome. Extra-Edge Point: Nelson 21 st Ed says that the current average life expectancy in Down Syndrome is 50-55 years. Reference: OP Ghai 10 th Edition, Page 668, Nelson 21 st Edition, Chapter 98.2