SNP Shot: Genomic Insights

Isolated growth hormone deficiency (IGHD) occurs when the body doesn't produce enough growth hormone, a protein crucial for the healthy development of bones and tissues. Individuals with IGHD typically experience slower than expected growth and are unusually short, often noticeable in early childhood.

IGHD is classified into four types based on the severity, the specific gene affected, and how it's inherited.

Type IA IGHD is the most severe, characterized by a complete absence of growth hormone. Babies with type IA are noticeably shorter than average at birth, with growth failure evident from infancy.

Type IB IGHD involves producing very low levels of growth hormone. While individuals with type IB also have short stature, the growth failure is generally less severe than in type IA. The growth issues typically become apparent in early to mid-childhood.

Type II IGHD is characterized by very low growth hormone levels and variable short stature. Growth issues usually appear in early to mid-childhood. Approximately half of those with type II have pituitary hypoplasia, a condition where the pituitary gland (which produces growth hormone) is underdeveloped.

Type III IGHD is similar to type II, involving very low growth hormone levels and short stature of varying severity, with growth issues becoming apparent in early to mid-childhood. In addition, individuals with type III may have a weakened immune system, leading to frequent infections, due to a shortage of B cells (agammaglobulinemia), which are crucial for fighting infections.

Inheritance:

The inheritance pattern of IGHD varies depending on the type. Types IA and IB follow an autosomal recessive pattern. This means both parents must carry a mutated copy of the GH1 or GHRHR gene for their child to inherit the condition. The parents themselves usually don't show symptoms. Type II can be autosomal dominant, requiring only one mutated copy of the GH1 gene to cause the disorder. Type II can also arise from a new mutation in the GH1 gene, even without a family history. Type III, caused by mutations in the BTK gene, follows an X-linked recessive pattern. The BTK gene is located on the X chromosome. Males, having only one X chromosome, are more likely to be affected by X-linked recessive disorders, as only one mutated copy is needed. Females, with two X chromosomes, would need mutations in both copies. Fathers cannot pass X-linked traits to their sons.