ESPE Abstracts

Introduction: Noonan syndrome-like syndrome with loose anagen hair (NSLH) is a RASopathy due to a missense mutation in the SHOCK2 gene. NSLH is distinguished by facial dysmorphisms, growth retardation, various neurocognitive impairment, and cardiac defects. Extremely short stature is frequently observed in patients with SHOC2 gene mutation. Treatment by growth hormone (GH) due to moderate GH deficiency or IGF-1 due to GH insensitivity may be insufficient. We report on a genetically diagnosed NSLH patient manifesting severe short stature with refractory treatment with GH and mecasermin.

Case report: The presented case is a girl born 3rd in a family of healthy parents (target height -1.15 SD) at 37 gestation weeks. The birth weight was 3474 g (1.0 SD), length – 48 cm (-0.83 SD). An atrial septal defect was diagnosed at birth. Karyotype was 46, XX. At the first endocrinologist evaluation at 12 months: a length of 64 cm (-3.68 SD), a weight of 6.5 kg (-3.86 SD), and continuous growth retardation were observed, and evaluation was performed at the 3 yr. age: IGF-1 7.5 nmol/L (<-2 SD), normal thyroid function, and retarded bone age (-1 y.). Hypopituitarism was diagnosed and treatment with recombinant human GH (rhGH) was started after GH stimulation tests: GH peaks were 9.51 mU/L and 16.45 mU/L. Height at the beginning (4 yr. of age) of rhGH treatment was 86 cm (-4.61 SD). According to physical examination and dysplastic features, the genetic syndrome was suspected, and NSLH was diagnosed at 11 yr. Due to poor response to rhGH, treatment stopped at the 12 yr. (height 117.4 cm (-4.36 SD)). During treatment with rhGH, the IGF-1 concentrations remained low, severe primary IGF-1 deficiency was diagnosed, and treatment with mecasermin was prescribed with increasing doses 40–120 µg/kg twice daily for 3 years. Height at the beginning (13 yr.) of rhIGF-1 treatment was 124 cm (-5.18 SD). Nevertheless treatment, her growth velocity was between 2.25–4.25 cm/yr. At 16 yr., the treatment was discontinued achieving a height of 132 cm (-5.25 SD).

Conclusion: In this case, we present a poor treatment efficiency of rhGH and IGF-1 for the patient with NSLH affected due to SCHOC2 mutation. The deepest literature review of NSLH and treatment outcomes for growth is needed to compose the genotype-phenotype relationship and treatment response in NSLH.