ESPE Abstracts

Introduction: Widespread availability of genetic testing has dramatically impacted clinical practice in some developed countries, changing the current perspectives of preventive medicine and sometimes raising more questions than answers and creating research opportunities.

Case report: We report the case of a 6-year-old boy with familial history of neuropathy who was first addressed to the Neurology Department due to a developmental delay regarding walking, frequent falling and feet numbness. He had a family history of Charcot-Mary-Tooth disease, which had been diagnosed on his mother and grandmother, who also presented with short stature, at 147 cm (the mother’s height was normal at 159 cm). The patient’s weight and stature had progressed within the normal range. Dysmorphic features were present, namely frontal bossing, mid-facial hypoplasia and bilateral knee hypoplasia. An electromyogram revealed a chronic neuropathic pattern. After multiple exams and thorough investigation, mendeliome sequencing performed on the patient and other affected relatives uncovered a pathogenic variant in the DYNC1H1 gene, related to Charcot-Marie-Tooth disease and muscular spinal atrophy, as well as a pathogenic variant in the ACAN gene. While the former was also found in the patient’s mother, aunts and grandmother, the latter was only shared between the patient, his mother and aunts. After the results, at age 10, the patient was addressed to an endocrinology appointment. He presented a height at -1.8 SD and body mass index (BMI) at +3 SD. Bone age was in accordance with his chronological age. During follow up, stature was progressing at around -1.5 SD and there was a slight improvement of the patient’s BMI. As expected, a progressive advance of bone age was noted.

Conclusion: Short stature and advanced bone age are hallmarks of ACAN mutations. In this case, the absence of short stature both in the patient and affected family members raises questions regarding genetic segregation and penetrance. Nonetheless, careful follow up is warranted, since pubertal growth is possibly compromised and chronic complications, such as early onset osteoarthritis and lumbar disc herniation, have been reported in affected patients.