EFFICACY OF RECOMBINANT GROWTH HORMONE THERAPY IN TWO PATIENTS WITH THE FAMILIAL FORM OF SCHAAF-YANG SYNDROME

Abstract

Schaaf-Yang syndrome (SYS) is an autosomal dominant multisystem disorder with early clinical overlap with Prader–Willi syndrome. Key features include hypotonia, joint contractures, autism spectrum disorders, intellectual disability, and growth retardation. The feasibility and efficacy of recombinant human growth hormone (rhGH) therapy in SYS remain under discussion. This study aimed to evaluate the clinical and laboratory efficacy of recombinant human growth hormone therapy in 2 siblings with Schaaf-Yang syndrome.

Materials and methods. Two siblings with SYS were examined: an 11.10-year-old boy and his 18.2-year-old sister. Serum GH, IGF-1, TSH, free T4, and prolactin levels were measured by ELISA. Bone age was assessed using the Greulich–Pyle method. Anthropometric parameters were evaluated according to WHO standards. Molecular genetic testing identified a heterozygous nonsense variant in the MAGEL2 gene (c.2873G>A, p.Trp958*), inherited from the father, confirming the diagnosis of SYS in both patients. Both received rhGH in pediatric and adult dosage and the efficacy was assessed.

Results. The boy presented with congenital finger contractures, persistent hypotonia, feeding difficulties in infancy, chronic constipation, gastroesophageal reflux, and severe psychomotor delay (independent sitting at 2.5 years, walking at 3.8 years). Baseline GH was 0.84 ng/mL. rhGH therapy was initiated at 0.035 mg/kg/day. After 15 months, height increased from 116 to 128 cm (SDS −4.8 to −4.2), weight from 21.1 to 26.5 kg, and growth velocity reached +12 cm. IGF-1 increased from 20.0 to 126.0 ng/mL (SDS −5.28 to −2.40), and bone age progressed from 7 to 11 years. Marked improvements were noted in muscle strength, physical activity, speech development, communication, and self-care skills. The sister exhibited intellectual disability, social maladaptation, short stature, muscle weakness, obesity with hyperphagia, atopic dermatitis, and secondary amenorrhea. Baseline height was 134 cm (SDS −4.5), bone age 18 years, IGF-1 80 ng/mL (SDS −2.8), and GH 0.9 ng/ml, with normal thyroid and prolactin levels. She received rhGH 0.3 mg/day combined with estradiol and dydrogesterone. After 15 months, fat mass decreased from 51% to 45%, muscle mass increased from 28 to 31.7 kg, and body weight decreased from 68.8 to 58.0 kg. Clinical improvements included reduced appetite, increased physical activity, better social adaptation, reduced behavioral disturbances, and normalization of the menstrual cycle.

Conclusions. Patients with Schaaf-Yang syndrome demonstrate clinical and laboratory signs consistent with growth hormone deficiency. Recombinant human growth hormone therapy appears safe and effective in both pediatric and adult patients, significantly improving growth parameters, body composition, and psycho-emotional functioning.