Endocrine Abstracts

JOINT91918

Introduction: 18p deletion, first described by Jean de Grouchy in 1963, is a rare chromosomal anomaly caused by the partial or complete loss of genetic material on the short arm of chromosome 18. This syndrome occurs in approximately 1 in 50,000 live births and exhibits various phenotypic features, including mild to moderate intellectual disability, short stature, speech delay, and facial dysmorphisms. Additionally, this syndrome has been associated with autoimmune diseases such as autoimmune thyroid disorders, rheumatoid arthritis, celiac disease, lupus, and alopecia. However, the molecular mechanisms explaining the connection between 18p deletion syndrome and autoimmunity remain unclear.

Case Report: A 3-year-8-month-old girl presented with complaints of polydipsia and polyuria. Physical examination revealed dysmorphic features, including a round face, broad nasal bridge, long philtrum, hypertelorism, and a short neck. Cardiovascular evaluation detected a 3/6 systolic murmur. Laboratory investigations showed glucose 339 mg/dL, insulin 11.43 mU/l, C-peptide 1.26 ng/mL, HbA1c 9.4%, and positive Anti-GAD and Anti-insulin antibodies. The patient was diagnosed with Type 1 Diabetes Mellitus (T1DM) and insulin therapy was initiated. Further evaluations revealed bilateral sensorineural hearing loss, myopia, IgA deficiency, and subaortic stenosis. At the age of five, epilepsy developed, and antiepileptic therapy was started. Array CGH analysis revealed a 13.7 Mb deletion in the 18p11.32-p11.21 region (arr[hg19]18p11.32p11.21(148963-13875138)x1). During follow-up, elevated Anti-TPO and Anti-TG antibodies led to the diagnosis of Hashimoto’s thyroiditis, and levothyroxine therapy was initiated.

Discussion: 18p deletion syndrome is a rare genetic condition with a broad spectrum of clinical features. Common findings include short stature, facial dysmorphisms, intellectual disability, skeletal deformities, and ophthalmologic problems. 18p deletion syndrome is associated with early-onset autoimmune thyroid diseases, T1DM, and other immune system disorders. Genetic analysis highlighted the loss of PTPN2, PTPRM, ADCYAP1, USP14, and LPIN2 genes. PTPN2 plays a critical role in regulating immune responses, increasing the risk of T1DM and autoimmune diseases. PTPRM negatively regulates STAT3 phosphorylation; its loss may lead to increased Th17 cell fractions and accelerated autoimmune processes. ADCYAP1 protects beta cells from cytokine-induced apoptosis, while USP14 maintains cellular homeostasis by preventing beta-cell apoptosis. LPIN2 regulates lipid metabolism and inflammatory responses; its deficiency may cause immune system hyperactivity, triggering T1DM. The loss of these genes has been highlighted as potential mechanisms underlying autoimmunity and diabetes pathogenesis.

Key words: 18p deletion syndrome, Type 1 Diabetes Mellitus, Hashimoto’s thyroiditis, Autoimmune diseases