3-M syndrome is a rare autosomal recessive growth disorder characterized by severe growth retardation, low birth weight, characteristic facial features, and skeletal anomalies, for which three causative genes (CUL7, OBSL1, and CCDC8) have been identified. We herein report two Korean siblings with 3-M syndrome caused by two novel OBSL1 mutations, and describe the effect of a combined treatment with growth hormone (GH) and a gonadotropin-releasing hormone (GnRH) agonist. A 7-year-old girl with short stature (-3.37 standard deviation score, SDS) and breast budding presented with subtle dysmorphic features, including macrocephaly, frontal bossing, a triangular face, prominent philtrum, full lips, a short neck, and fifth-finger clinodactyly. GnRH stimulation test revealed a pubertal pattern and advanced bone age of 8 years and 10 months. Her older sister, aged 10 years and 9 months, had experienced an early menarche, and had an advanced bone age (13.5 years) and predicted adult height of 142 cm (-4.04 SDS). Targeted exome sequencing identified that the siblings had two heteroallelic mutations in OBSL1. Both siblings underwent a combination therapy with GH and a GnRH agonist. A height gain was noted in both siblings even after short-term treatment. To fully elucidate the effects of the combined therapy, a larger cohort should be analyzed following a longer treatment period. However, such an analysis would be challenging due to the rarity of this disease.
Keywords: 3-M syndrome; OBSL1; Short stature; growth hormone; precocious puberty.
© Copyright: Yonsei University College of Medicine 2020.