A case report of Noonan syndrome-like disorder with loose anagen hair 2 treated with recombinant human growth hormone

Am J Med Genet A. 2020 Aug;182(8):1967-1971. doi: 10.1002/ajmg.a.61638. Epub 2020 Jun 1.


Protein phosphatase 1 catalytic subunit beta (PPP1CB) is a disease-causing gene of Noonan-like syndrome, which acts via the RAS/MAPK pathway. To date, only 17 patients diagnosed with PPP1CB-related Noonan-like syndrome have been reported around the world, with few reports in Asia. Twelve reported patients are of short stature and only one patient was treated with growth hormone (GH); however, follow-up data is lacking. To the best of our knowledge, this is the first reported patient with complete recombinant human growth hormone (rhGH) treatment follow-up data; the patient has a de novo c.146C>G (p.Pro49Arg) mutation in the PPP1CB gene. The hair pattern of the patient (coarse, curly, slow growing, and fragile) combined with Noonan dysmorphic features, developmental delay, and congenital heart disease, are highly consistent with the typical features observed in Noonan syndrome-like disorder with loose anagen hair 2 (NSLH2). rhGH treatment, administered for 3 years and 8 months, promoted the patient's linear growth. Our findings expand the data regarding the treatment of short stature in patients with NSLH2 caused by PPP1CB mutation. Clinical manifestation, growth and development process, and rhGH therapy effect data will aid in future revision of the relevant diagnosis and treatment guidelines.

Keywords: PPP1CB; Noonan syndrome-like disorder with loose anagen hair 2 (NSLH2); linear growth; recombinant human growth hormone; treatment.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease
  • Heart Defects, Congenital / complications
  • Heart Defects, Congenital / drug therapy
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / pathology
  • Human Growth Hormone / administration & dosage*
  • Humans
  • Loose Anagen Hair Syndrome / complications
  • Loose Anagen Hair Syndrome / drug therapy*
  • Loose Anagen Hair Syndrome / genetics
  • Loose Anagen Hair Syndrome / pathology
  • Male
  • Noonan Syndrome / complications
  • Noonan Syndrome / drug therapy*
  • Noonan Syndrome / genetics
  • Noonan Syndrome / pathology
  • Phenotype
  • Protein Phosphatase 1 / genetics*


  • Human Growth Hormone
  • PPP1CB protein, human
  • Protein Phosphatase 1