ABSTRACT
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.
Subject(s)
Human Growth Hormone/administration & dosage , Loose Anagen Hair Syndrome/drug therapy , Noonan Syndrome/drug therapy , Protein Phosphatase 1/genetics , 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 , Humans , Loose Anagen Hair Syndrome/complications , Loose Anagen Hair Syndrome/genetics , Loose Anagen Hair Syndrome/pathology , Male , Noonan Syndrome/complications , Noonan Syndrome/genetics , Noonan Syndrome/pathology , PhenotypeABSTRACT
BACKGROUND: Noonan-like syndrome with loose anagen hair is one of the RASopathies characterized by Noonan syndrome-like features with unique ectodermal abnormalities. This syndrome is caused by mutations in the SHOC2 gene. We encountered a patient with moyamoya syndrome associated with Noonan-like syndrome with loose anagen hair presenting with transient ischemic attacks. PATIENT DESCRIPTION: A 6-year-old girl was diagnosed with Noonan-like syndrome with loose anagen hair because of profound short stature and ectodermal anomalies such as sparse and easily pluckable hair. A heterozygous mutation of c.4A>G (p.S2G) in the SHOC2 gene was identified, and recombinant human growth hormone therapy was initiated at 8 years of age. At age 10, she manifested recurrent left hemiplegia. Moreover, cerebrovascular imaging revealed occlusion or narrowing of both internal carotid arteries and both middle cerebral arteries with distal moyamoya-like vessels. She is treated with aspirin and calcium channel blocker. CONCLUSIONS: We describe the first case of Noonan-like syndrome with loose anagen hair associated with moyamoya syndrome, although it has been reported to be associated with a few cases of other RASopathies, including Noonan, cardiofaciocutaneous, and Costello syndromes. This report emphasizes the associations between cerebrovascular anomalies and Noonan-like syndrome with loose anagen hair.
