Endocrine Abstracts

JOINT2743

Introduction: Spondylocostal dysostosis is a genetically inherited disorder characterized by malformations of the ribs and vertebrae. Heterozygous and biallelic variants in TBX6 gene have been linked to vertebral and rib malformations, as well as spondylocostal dysostosis. In this case report, we aimed to contribute to the literature by presenting the clinical findings of our patient with TBX6 gene variant, one of the rare causes of spondylocostal dysostosis.

Case Report: A 14-year-old male patient was referred to the endocrinology clinic due to short stature. His parents were first-degree relatives. The mother’s height was 162.1 cm, and the father’s height was 169.2 cm, with a target height of 172.15 cm (-0.66 SDS). On physical examination, the patient’s weight was 41.5 kg (-1.7 SDS), height was 142.5 cm (-3.02 SDS), BMI was 20.4 (-0.05 SDS), and head circumference was 54 cm (-1.33 SDS). His pubertal stage was Tanner A+P1, with testicular volumes of 4 ml bilaterally. Laboratory investigations, including complete blood count, thyroid function tests, and biochemical analyses, were within normal limits. Serum IGF-1 was 152 µg/L (115-489), and IGFBP3 was 3.85 mg/L (3.21-6.93). Due to severe short stature, a growth hormone stimulation test revealed a peak GH level of 11.2 µg/L (normal). Urinary mucopolysaccharide excretion was normal, ruling out mucopolysaccharidosis. Whole exome sequencing (WES) identified a likely pathogenic (NM_004608.4) heterozygous c.2T>A p.Met1Lys missense variant in the TBX6 gene. It was determined that the detected variant was inherited from the father, who exhibited similar clinical features.

Discussion: According to The Human Gene Mutation Database Professional 2023.4, a total of 84 different variants have been reported in the TBX6 gene, including 34 missense/nonsense, 6 splicing, 1 regulatory, 9 small deletions, 8 small inversions, 21 gross deletions, and 5 gross insertions. Our case presented with a clinically relevant and frequently observed missense variant in this gene. The identified variant was not found in the gnomAD and ClinVar databases and was classified as likely pathogenic according to ACMG criteria. Phenotypes associated with TBX6 gene variants include short stature, short neck, rib anomalies, scoliosis, hemivertebrae, and butterfly vertebrae. Recognizing spondylocostal dysostosis in the prenatal period allows for the exclusion of spondylothoracic dysostosis, assessment of recurrence risk in siblings, and provision of genetic counseling. In the postnatal period, early diagnosis facilitates physiotherapy to improve quality of life and increase lifespan. Additionally, surgical intervention can be performed for stabilization of chest wall and spinal deformities.

Keywords: Short stature, TBX6 Gene