The majority of children with Kabuki will fall in the lower percentile for growth. Postnatal growth retardation means the children are usually born with normal body lengths but their growth following birth is at a slower rate than the norm. The causative factors for growth retardation in Kabuki syndrome have not yet been clarified. Some children, when tested, have shown partial growth hormone level deficiencies and have been given growth hormone injections for varying lengths of time. It appears that for some of these children with proven growth hormone deficiencies, the therapy has helped them attain increased linear growth.
Growth is influenced by the endocrine system.
There are a percentage of children with Kabuki who have endocrinological abnormalities.
What exactly is the endocrine system?
The endocrine system consists of various glands that produce hormones, which are delivered directly into the blood. Each of the glands of the endocrine system has one or more specific functions, but they are all dependent upon one another to maintain a normal hormonal balance in the body.
The pituitary gland (also called the hypophysis in the articles), which is about the size of a pea, lies at the base of the brain and is called the master gland because it regulates the functions of other endocrine glands. It also has some functions of its own such as controlling the body's growth through the growth hormone.
Some pituitary hormones that directly affect other glands are:
1)thyroid-stimulating hormone (TSH), which stimulates the thyroid gland
2)adrenocorticotropic hormone (ACTH), which affects the adrenal gland
3)the gonadotropic hormones (FSH, LH, and LTH), which have a role in the development and proper functioning of the gonads (ovary and testes)
Number 1, the thyroid gland, is situated in the neck and produces hormones that are vital in maintaining normal growth and metabolism. It also stores iodine.
Number 2, the adrenal glands, are situated above the kidneys and secrete at least 26 hormones, including epinephrine, corticosterone, and aldosterone. They are vital to the protection of the body during stress and danger, and to the adaptation of the body to changes in its environment.
Number 3, the gonads (or sex glands), consist of the testes in the male and the ovaries in the female. Besides producing sperm and ova, they manufacture the androgens and estrogens, hormones responsible for the special characteristics of the male and female.
Another group of cells belonging to the endocrine system are the specialized cells scattered throughout the pancreas, called the 'islands of Langerhans'. These cells secrete the hormone insulin, which is necessary for proper utilization of carbohydrates - therefore decreasing blood sugar. The cells also secrete glucagon, a hormone that has the opposite effect of insulin in that it stimulates glycogenolysis in the liver (changing carbohydrates into glucose) - therefore increasing blood sugar.
So now that we understand a little what the endocrine system consists of, what does this mean in reference to Kabuki?
Well, it doesn't seem unlikely that since endocrinological abnormalities have been associated with Kabuki that we should see a whole range of hormonal-dependent abnormalities, including precocious puberty, growth retardation, diabetes, etc. But I don't think the professionals know yet what triggers the endocrine anomalies.
Because the glands of the endocrine system are so dependent upon one another, where do the problems lie? What mechanisms are causing the anomalies? Hopefully, by testing, by documenting, and by publishing the results, we will eventually find some answers.
Genetic Articles on Growth Hormone:
Kabuki syndrome and growth hormone deficiency: description of a case treated by long-term hormone replacement - Clinical Dysmorphology Jan;11(1) pp. 71-72 2002 Author: Gabrielli O, Bruni S, Bruschi B, Carloni I, Coppa GV
Long-term hormone replacement therapy in two patients with Kabuki syndrome and growth hormone deficiency - Minerva Pediatr Jan-Feb;52(1-2) pp. 47-53 2000 Author: : Gabrielli O, Carloni L, Coppa GV, Bedeschi MF, Petroncini MM, Selicorni A
Growth Hormone Deficiency and Premature Thelarche in a Female Infant with Kabuki Makeup Syndrome - Hormone Research 43 pp.303-306 1995 Author: Devriendt K, et al
A case of Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction - Acta Paediatrica Japonica 36 pp.412-415 1994 Author: Tawa R, et al.
A Case of Kabuki Make-Up Syndrome Associated with Growth Hormone Deficiency - Clinical Pediatric Endocrinology 2 pp. 13-16 1993 Author: Satoh M, et al
Growth Hormone Insufficiency in Kabuki Make-up Syndrome - Acta Paediatrica Scand (Suppl) 370 pp.196 1990 Author: Kawada Y, et al.
Following is a quote from the article, Growth Hormone Deficiency and Premature Thelarche.....
Quote:
At birth this girl was of normal size, but a marked growth failure was observed during infancy. Repeated GH (growth hormone) stimulation test consistently showed a lowered GH response (below 10 ng/ml), suggestive of partial GH deficiency. The neonatal hypoglycemia, truncal obesity, depressed serum T3 concentrations, undetectable IGF-I levels and the remarkable growth response to rhGH therapy corroborate the diagnosis of GH deficiency. The impressive response to exogenous GRF (growth hormone-releasing factor) indicates that the GH deficiency is of hypothalamic origin, possibly due to GRF deficiency. In this regard, it is of particular interest that the pituitary stalk appeared to be intact on magnetic resonance imaging (MRI), and that no major malformations of this region could be demonstrated.
Postnatal growth deficiency is a major criterion of the KMS as the reported incidence is 80%. In this girl with the KMS the postnatal growth retardation was documented to be caused, at least in part, by GH deficiency. Two other patients with KMS and partial GH deficiency have been reported, one of whom was treated with GH apparently without significant effect.
This girl presented premature breast development without other signs of systemic estrogen effect, i.e. no macroscopic vulvar estrogenization, no growth acceleration or advanced bone age. Neither was there axillary or pubic hair development. In addition, breast size did not augment over a period of 2.5 years. The basal serum FSH level was elevated with a normal basal LH level and predominant FSH response to LH-RH administration was present. These clinical and biochemical findings are consistent with the diagnosis of premature thelarche. Premature thelarche is a variant of precocious sexual maturation, and can be caused by an activation of the hypothalamopituitary axis, resulting in a predominant FSH secretion, as in this patient. It has been suggested that true central precocious puberty and premature thelarche represent the extreme variants within the spectrum of precocious hypothalamopituitary activation. In the review study of Niikawa et al., premature thelarche was present in 23% of the girls with KMS. Endocrinological studies have been reported in three patients; two of them appear to present isolated premature thelarche, whereas the third was documented to have true central precocious puberty. The precise etiology of the precocious sexual maturation in KMS girls is currently unknown.
In this girl, no deficiencies of other pituitary hormones were identified. Interestingly, a boy with the KMS and both central diabetes insipidus and GH neurosecretory dysfunction has recently been reported. The coincidence of premature thelarche and growth hormone deficiency in this girl and the occurrence of hypothalamopituitary dysfunction in other children with the KMS warrant further neuroendocrine studies in children with the KMS.
Unquote
So it seems they're saying that this particular girl had early breast development (thelarche), but no other signs of early puberty (precocious puberty). And that in other studies done previously by Niikawa, 23% of the girls had premature thelarche. Of those girls, 3 had endocrinlogical studies done (blood drawn to detect various hormonal levels) which showed 2 had only early breast development and 1 had 'true central precocious puberty'. I'm not sure what's meant by 'true', but I'm assuming it means the girl had not only early breast development, but also all other signs of puberty (increased growth, widening of hips, appearance of axillary and pubic hair, and the onset of menstruation).
They conclude that the precise cause of the premature sexual maturation is not currently known, but that the fact that so many children are showing endocrine-based anomalies warrants further studies.