Endocrine Abstracts

JOINT359

Growth hormone deficiency (GHD) is a disorder of growth hormone secretion from the pituitary gland. Its clinical presentation can include neonatal hypoglycemia, prolonged jaundice, and midfacial defects. However, in children, it sometimes presents only as short stature and/or growth deceleration. GHD is diagnosed when children with short stature (<2 standard deviation score [SDS] relative to the general population) show delayed bone age and peak growth hormone levels of less than 10 ng/ml in at least two growth hormone stimulation tests. For patients who show growth faltering and/or a suboptimal response even when treated with recombinant human growth hormone, additional phenotypes, such as severe short stature and body disproportion, should be assessed, and additional diagnoses should be considered. A 5-year-old girl visited the Department of Pediatrics because of short stature and low weight. She had previously undergone karyotyping and single nucleotide polymorphism (SNP) array testing because of developmental delay, intellectual disability, short stature, and distinctive facial dysmorphisms, including frontal bossing, deep-set eyes, low-set ears, depressed nasal bridge, and short philtrum after birth. The results at the time showed no abnormal finding, but GHD was diagnosed in growth hormone stimulation tests. She was being treated with a high dose of growth hormone (50 μg/kg/day) for GHD in children born SGA, and showed a poor rate of growth even after 5 years of treatment, with a height SDS of -3.98 (formerly -4.05). However, following next-generation sequencing (NGS)-based whole exome sequencing (WES), the patient was diagnosed with Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome (OMIM: 617140), due to a heterozygous mutation in SON. She is currently continuing growth hormone treatment, as well as receiving pediatric rehabilitation and orthopedic care. Recently, following advances in molecular genetic techniques, genetic causes for many endocrinological diseases have been discovered; hence, genetic testing is commonly used in the diagnosis and genetic counseling of endocrinological diseases. Guidelines for the genetic testing of children with short-stature have also been established. Generally, this disease is unrelated to GHD; however, in 2020, a case of ZTTK syndrome accompanied by GHD with a unique presentation was reported. We believe that this case may be useful references for expanding the genotype-phenotype map. Here, we report the case of ZTTK syndrome with GHD diagnosed by WES in a patient with GHD who did not respond well to GH treatment.