Endocrine Abstracts

JOINT745

Background: Girl six months old was referred in Sept. 2020 to the pediatric endocrinologist, due to short stature approximately -6 SD and skeletal changes. Antenatally: growth retardation, acute section in week 29+4, SGA was noted. Birth weight was 745 gram, birth length was 33 cm. Head circumference normal. Apnea episode early. Initial feeding difficulties. Bilateral conductive hearing loss was discovered.

Material: X-ray findings: Full body X-ray showed shorter humerus, ulna and femur. Single longitudinal vertebrae with suggested fish shape. Lab. values: Jon-Calcium 1,38 mmol/l, Phosphate 2,0 mmol/l, Mg 0,97 mmol/l, TSH 11 mIE/l, T4 17 nmol/l, Alat 0,35 µkat/l, ALP 3,4 µkat/l, PTH 1,07 pmol/l- new sampling 3,3 pmol/l, 25-OH Vitamin D 101 nmol/l (new sampling 84 nmol/l).

Results: Microarray and skeletal dysplasia panel testing returned negative results, prompting whole-genome analysis. This analysis identified two pathogenic DNA variants in the SLC10A7 gene in a compound heterozygous state: c.722-16A>G and c.773+1G>A. These variants lead to the production of a truncated and dysfunctional protein, impairing glycosylation. The parents were found to be heterozygous carriers, each for one of the variants. The findings are consistent with the condition "Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis" (OMIM# 618363). This rare skeletal dysplasia is caused by a congenital glycosylation defect and follows an autosomal recessive inheritance pattern. Associated features may include abnormal facial characteristics, hearing impairment, and intellectual disability. To date, this diagnosis has been reported in only a small number of patients. In January 2025 the girl is followed in the endocrine clinic, neonatal clinic including psychologist contact, the audiologist, specialist dentist, pediatric orthopedist, and nutrition team. Now at age 4 her height is 91,9 cm (-3 SD) and weight is 14 kg (-2 SD). She has an increasingly abundant vocabulary and has become more independent in her physical movement.

Conclusion: Whole genome sequencing (WGS) analysis revealed an unusual form of skeletal dysplasia caused by a congenital glycosylation defect. The condition is characterized by disproportionate short stature, defective tooth enamel formation and sometimes severe scoliosis. In cases with unclear symptoms and suspected syndrome perform WGS analysis and follow the patient over time.