Kowarski syndrome

Overview

Kowarski syndrome is a rare form of isolated growth hormone deficiency (IGHD) that leads to short stature in children due to insufficient secretion of growth hormone (GH) despite a structurally normal pituitary gland. Unlike other forms of GH deficiency, Kowarski syndrome is characterized by a partial or functional deficiency, where GH levels may appear normal or borderline during standard tests but are insufficient to support normal growth. It is named after Dr. Andrzej Kowarski, who first described the condition in the context of growth disorders.

Causes

Kowarski syndrome is typically caused by a dysfunction in the hypothalamic-pituitary axis that impairs the pulsatile secretion or bioactivity of growth hormone. Potential underlying causes include:

• Genetic mutations affecting GH regulation or action

• Abnormalities in GH-releasing hormone (GHRH) signaling

• Altered GH bioactivity (i.e., biologically inactive forms of GH despite normal levels)

• Idiopathic (no identifiable cause in many cases)

The condition is usually congenital and non-progressive, meaning it is present from birth and does not worsen over time.

Symptoms

The primary symptom of Kowarski syndrome is growth failure. Affected children typically present with:

• Short stature significantly below the age- and sex-adjusted growth charts

• Normal body proportions (unlike some skeletal dysplasias)

• Delayed bone age compared to chronological age

• Delayed puberty (in some cases)

• Normal intellectual development and cognitive function

• No signs of other systemic illness or pituitary hormone deficiencies

Because GH levels may appear normal in some tests, diagnosis can be delayed or misinterpreted without specialized evaluation.

Diagnosis

Diagnosing Kowarski syndrome involves comprehensive evaluation to confirm a functional growth hormone deficiency. Key diagnostic steps include:

• Growth monitoring: Regular plotting of height and growth velocity on standardized growth charts

• Bone age assessment: X-ray of the left hand and wrist to determine skeletal maturity

• GH stimulation tests: Pharmacologic testing using agents like clonidine, arginine, or insulin to evaluate GH secretion

• IGF-1 and IGFBP-3 levels: May be low or borderline, indicating impaired GH function

• MRI of the brain: To assess the hypothalamic-pituitary region for anatomical abnormalities (usually normal in this syndrome)

Diagnosis may require interpretation by a pediatric endocrinologist familiar with subtle forms of GH deficiency.

Treatment

Treatment of Kowarski syndrome focuses on replacing deficient growth hormone and monitoring growth progress. Key components of management include:

• Recombinant human growth hormone (rhGH): Administered via daily subcutaneous injections to stimulate normal growth

• Regular monitoring: Assessment of height, growth velocity, IGF-1 levels, and bone age every 3–6 months

• Adjustment of GH dosage: Based on growth response and laboratory parameters

• Nutritional and psychological support: To address any associated psychosocial or developmental concerns

Treatment is generally continued until final adult height is achieved or bone growth plates have closed.

Prognosis

With early diagnosis and appropriate GH therapy, children with Kowarski syndrome can achieve normal or near-normal adult height. The condition does not typically affect lifespan, intelligence, or overall health. Delayed treatment may result in suboptimal growth outcomes, emphasizing the importance of timely recognition and intervention. Long-term prognosis is excellent with consistent therapy and monitoring.