Genetic basis of Congenital Adrenal Hyperplasia - in cats is a rare autosomal recessive inherited endocrine disorder caused by mutations in the CYP11B1 gene, which encodes the enzyme 11β-hydroxylase. This enzyme is critical for cortisol synthesis in the adrenal glands. The mutation identified in affected cats is a missense single nucleotide polymorphism (G>A) in exon 7 of CYP11B1, resulting in an arginine-to-glutamine amino acid substitution. Deficiency of 11β-hydroxylase disrupts normal steroid biosynthesis similar to human 11β-hydroxylase deficiency CAH. Genetic testing is available but rare due to the condition's rarity.
Pathophysiology - The 11β-hydroxylase enzyme catalyzes the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone in the adrenal cortex. Deficiency leads to: Decreased cortisol and corticosterone production, causing loss of negative feedback on adrenocorticotropic hormone (ACTH) secretion. Compensatory adrenal hyperplasia due to raised ACTH, producing excess steroid precursors upstream of the block. Hormonal imbalances manifesting as abnormal sex steroid production and mineralocorticoid excess (can cause hypertension in humans). Clinical signs in affected cats resemble those of human 11β-hydroxylase deficiency CAH.
Complications - Clinical manifestations reported in cats include: Signs of hormone imbalance and adrenal dysfunction. Possible ambiguous genitalia or disorders of sexual development (DSD), particularly in XX individuals. Progressive adrenal enlargement (hyperplasia). Symptoms reflecting disrupted cortisol and mineralocorticoid balance. Due to limited case reports, the full spectrum of clinical signs in cats is not comprehensively described but likely similar to other mammals.
Why This Matters to Breeders and Vets - Breeders: Although very rare, awareness of CAH due to CYP11B1 mutations is important for genetic screening in populations where the condition is detected. Avoiding carrier-to-carrier matings can prevent affected offspring. Veterinarians: Recognizing clinical signs of CAH and disorders of sexual development in cats can prompt appropriate genetic testing and endocrine evaluation. Confirmation aids diagnosis and informs prognosis and management. This disorder highlights the relevance of comparative endocrinology for diagnosis and treatment strategies
Summary - Congenital Adrenal Hyperplasia in cats is a rare autosomal recessive disorder caused by mutations in the CYP11B1 gene leading to 11β-hydroxylase deficiency. This enzyme defect impairs cortisol biosynthesis causing adrenal hyperplasia and hormonal imbalances with clinical signs including possible ambiguous genitalia and adrenal dysfunction. Genetic confirmation is possible and important for diagnosis, breeding management, and clinical care.
