Challenges in the care of individuals with severe primary insulin-like growth factor-I deficiency (SPIGFD): an international, multi-stakeholder perspective

Table 1 Summary of known genetic causes of SPIGFD

Affected gene	Details
IGFALS	Decreased serum ALS as a result of a defect in the IGFALS gene is associated with moderate short stature, delayed puberty and decreased serum IGF-I
GHR	Genetic defects in the GHR gene are the underlying cause of the classic form of SPIGFD, known as Laron syndrome
IGF-I	Homozygous mutations in IGF-I are very rare and are associated with severe short stature, deafness and insulin resistance
IκBα	IκBα mutations are associated with short stature and immunodeficiency
PAPPA2	Defects in PAPPA2 disrupt the release of circulating IGF-I, leading to varying degrees of short stature and insulin resistance
PTPN11	Activating PTPN11 mutations leads to dephosphorylation of STAT5B, causing downregulation of its activity and partial GH insensitivity
STAT5B	Mutations in STAT5B can lead to short stature, as well as a severe immune dysfunction

Source: Wit et al. 2012 [10]; Hwa et al. 2021 [11]
GHR, growth hormone receptor; IGFALS, insulin-like growth factor acid labile subunit; IGF-I, insulin-like growth factor I; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; PAPPA2, human pregnancy-associated plasma protease A2; PTPN11, tyrosine-protein phosphatase non-receptor type 11; SPIGFD, severe primary IGF-I deficiency; STAT5B, signal transducer and activator of transcription 5B

ISSN: 1750-1172