Endocrine Abstracts

JOINT2044

Introduction: Eighty percent of the height variation is explained by genetic factors, even though the standard medical evaluation of short stature (SS) relies upon physical examination and laboratory parameters and identifies a pathological cause of SS in 1–40% of individuals. This research aims to report a clinical case of a child with SS who underwent molecular investigation.

Case Report: HAS, 9 years 9 months, only daughter of a non-consanguineous couple, sought the pediatric endocrinology service complaining of SS. The child was a newborn with adequate weight and height for gestational age, with a slow growth speed from the second year of life. On physical examination, she presented: weight 18.5kg (-3.2SD), height 120cm (-2.64SD), syndromic features characterized by microcephaly (PC 45cm), epicanthus, broad nasal base, pointed and low-set ears and tooth agenesis. General laboratory tests were unremarkable; the Clonidine stimulation test was responsive (9 ng/ml), and bone age was 8 years and 10 months. A Generation Sequencing Panel for the complete exome was carried out, which showed a variant of uncertain significance (VUS) in heterozygosity in the COL9A3 and UBA5 genes. She started using GH at the age of 10 years 9 months, and at 11 years 11 months, she weighed 24.8 and had a height of 136.5 (-2.07SD), still without puberty signs and with normal intelligence.

Discussion: The COL9A3 gene encodes one of the three alpha chains of Type IX collagen. Patients with variants in homozygous present with Stickler syndrome, characterized by midface hypoplasia, myopia, hearing loss, and epiphyseal abnormalities. Patients with heterozygous mutations are reported to have multiple epiphyseal dysplasia type 3. The UBA5 gene encodes Ubiquitin-Like Modifier Activating Enzyme 5. Mutations in this gene can cause developmental and epileptic encephalopathy 44, which presents with the following symptoms: short stature, microcephaly, visual impairment, mental and motor impairment, seizures, and cerebellar atrophy. The conjunction of the two VUS in the aforementioned genes may justify the unique clinical case of this patient and was essential for the report that convinced the government of the state of Goiás to make GH treatment available to this child. Furthermore, the molecular diagnosis in cases of SS can end the diagnostic workup for the patient, it may alert the clinician to other medical comorbidities for which the patient is at risk, and it is extremely valuable for genetic counseling.