Growth in Kabuki Syndrome
Since the first large case series of individuals with Kabuki syndrome was published, it has been apparent that postnatal growth deficiency is common. In this series of 62 patients with Kabuki syndrome (primarily Japanese), growth parameters were noted to be normal at birth with growth deficiency occurring during the first year of life and becoming more marked with increasing age such that 83% of patients had evidence of growth deficiency (Niikawa N et al., 1988). Postnatal growth deficiency has been found in other large case series of individuals with Kabuki syndrome of different ethnic backgrounds ranging from 35% (Armstrong L et al., 2005), 61% (Kawame H et al., 1999), to 71% (Schrander-Stumpel et al., 2005). Mean final adult height for Japanese patients has been reported to be -2.3 standard deviations (Niikawa N et al., 1988).
There have been scattered reports of individuals with Kabuki syndrome who were diagnosed with growth hormone deficiency (Niikawa et al., 1988; Devriendt K at al., 1995; Kawame H et al., 1999; Gabrielli O et al., 2002; Armstrong L et al., 2005; Schrander-Stumper C et al., 2005). Efficacy of this therapy, however, has been variable with a “good response” to growth hormone described in one 9 year old boy treated for four years (Gabrielli et al, 2002), an increase in growth velocity in one 3 ½ year old girl treated for 6 months, to “no change in linear rate of growth” in another patient treated from 11 to 12 ½ years of age (Kawame H et al., 1999).
Treatment with human growth hormone is generally thought to be safe. However, it must be administered daily as an injection which raises the issue of cost-benefit ratio.
While growth hormone therapy is clearly indicated in individuals with documented growth hormone deficiency, its use in non-growth hormone deficient children is more controversial. As reviewed in a recent publication, most children treated with growth hormone will exhibit short term benefit, that is an increase in growth velocity, and final adult height will be increased in some (Collett-Solberg PF, 2011). However, large numbers of patients, including those with Kabuki syndrome, would need to be studied to assess the economic, social and psychological costs versus the benefit of gain in stature.
In summary, while postnatal growth deficiency is common, growth hormone deficiency does not appear to be a common feature of Kabuki syndrome. A reasonable approach would be to recommend a pediatric endocrinology evaluation for those individuals with Kabuki syndrome who exhibit short stature and poor growth velocity. The pediatric endocrinologist can then discuss the risks versus the benefits of a trial of growth hormone therapy with the family.
Armstrong L et al. (2005) Further delineation of Kabuki syndrome in 48 well-defined new individuals. Am J Med Genet 132A:265-272.
Collett-Solberg PF. (2011) Update in growth hormone therapy of children. J Clin Endocrinol Metab 96:573-579.
Gabrielli O et al. (2002) Kebuki syndrome and growth hormone deficiency: Description of a case treated by long-term hormone replacement. Clin Dysmorphol 11:71-72.
Devriendt K et al. (1995) Growth hormone deficiency and premature thelarchei in a female infant with Kabuki makeup syndrome. Horm Res 43:303-306.
Kawame H et al. (1999) Phenotypic spectrum and management issues in Kabuki syndrome. J Pediatr 134:480-5.
Niikawa N. et al. (1988) Kabuki make-up (Niikawa-Kuroki) syndrome: A study of 62 patients. Am J Med Genet 31:565-589.
Schrander-Stumpel C et al. (2005) Kabuki syndrome: Clinical data in 20 patients, literature review, and further guidelines for preventative management. Am J Med Genet 132A:234-243.