Analysis of the clinical and molecular characteristics of a child with achondroplasia: A case report

Abstract

Abstract. Achondroplasia (ACH) is a hereditary dwarfism caused by the disturbed proliferation and differentiation of growth plate chondrocytes, followed by impaired endochondral bone growth. ACH is caused by mutations in the gene encoding the transmembrane receptor, fibroblast growth factor receptor 3 (FGFR3). In total, >90% of patients with ACH have a G1138A mutation in the transmembrane domain of the FGFR3 gene. Patients with ACH usually have no growth hormone (GH) deficiency. The current study presents the case of a four-year-old male with clinical manifestations suggestive of ACH, including a large head, prominent forehead, short upper arms and legs, and short hands with fingers assuming a trident position. The patient showed normal responses to GH provocation tests with L-dopa (peak GH concentration, 42.38 ng/ml) and insulin (peak GH concentration, 23.29 ng/ml during hypoglycemia), but a blunted response to a GH provocation test with arginine (peak GH concentration, 7.31 ng/ml). Furthermore, the GH concentration during exercise was low (4.8 ng/ml). Magnetic resonance imaging revealed a decreased pituitary volume. Thyroid function tests and the levels of sex hormones (follicle stimulating hormone, luteinizing hormone, estradiol, prolactin and progesterone), cortisol and adrenocorticotropic hormone were normal. A heterozygous G1138A mutation within the FGFR3 gene was detected, confirming the diagnosis of ACH. Thus, recombinant human GH therapy (0.1 IU/kg/day) was initiated. At the six-month follow-up, the height, arm span-to-height ratio and lower limb length-to-height ratio of the patient had increased, while the head circumference had decreased. The present results corroborate the finding that the G1138A mutation within FGFR3 is the most common ACH-causing mutation in different populations. GH may be beneficial in the treatment of short stature in ACH patients with subnormal GH secretion.

Height Outcome of Recombinant Human Growth Hormone Treatment in Achondroplasia Children: A Meta-Analysis

“…Nine reports [16,17,37,38,39,40,41,42,43] were excluded from our analysis, because they used pituitary-extracted human GH. Three reports [44,45,50] were excluded from our analysis because the statistical software that was used required at least 2 patients for each group (i.e. study protocol).…”

“…Of the eligible articles, 34 English-language reports evaluated linear growth outcomes of ACH children using rhGH treatments [12,13,14,15,16,17,18,19,20,21,22,23,24,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50]. Nine reports [16,17,37,38,39,40,41,42,43] were excluded from our analysis, because they used pituitary-extracted human GH.…”

Severe pneumonia leading to death in an achondroplasic infant: a rare case report

“…Achondroplasia is caused, in virtually all of the cases, by a G380R mutation in fibroblast growth factor receptor 3 (FGFR3). 2 Being at risk for a variety of respiratory problems, increased frequency of airway malacia in infants and young children with achondroplasia is well known.…”