Abstract 125: Congenital hypothyroidism: Clinical profile and genetic abnormalities

Background: Congenital hypothyroidism (CH) is the most common inborn endocrine disorder and a common cause of preventable mental retardation. Primary CH may be associated with other systemic abnormalities (Syndromic CH). It may be due to specific genetic mutations leading to thyroid dysgenesis (TD) or dyshormonogenesis (TDH). Objectives: 1. To study the phenotypic profile of patients with CH harboring different gene mutations. 2. To evaluate the spectrum of mutations in candidate genes (PAX8, NKX2-1/TTF1, NKX2-5, FOXE1/TTF2, TSH-R, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD and TG) in cases with congenital hypothyroidism. Methods: In this cross-sectional study, after collection of preliminary data and baseline characteristics, individuals with CH were assessed for features of Syndromic CH. In the absence of syndromic features, they were broadly classified into Dyshormonogenesis and Dysgenesis (ectopic, agenesis, hypoplastic) based on unstimulated serum thyroglobulin and ultrasound of neck. They were subjected to genetic testing (PCR followed by Sanger sequencing) based on etiological classification. Results: Of the 40 individuals enrolled in the study, all but one individual had institutional delivery. However, only 15% had been subjected to neonatal TSH screening. The mean age at diagnosis was 6.1 + 10.53 months. Majority of the patients (67.5%) did not have clinical features of CH at diagnosis. Constipation was the most reported clinical feature in symptomatic CH. Delayed developmental milestones were noted in many. 1 had features of syndromic CH- Bamforth Lazarus syndrome, 17 were classified as thyroid dysgenesis and 22 as thyroid dyshormonogenesis. Mutations were detected in 37.5% of individuals. Mutations were detected in 9/22 (40.9%) individuals with TDH. 6 (30%) patients had multiple mutations. DUOXA2 (40%) was the most common mutation, followed by DEHAL1 (35%). Mutations were detected in 6/17 (35.29%) individuals with TD. 3 (20%) had multiple mutations. TTF-2 (53.3%) was the commonest mutation followed by PAX8 (26.6%). Conclusion: Syndromic CH was seen in only 1 individual. TDH was the most common etiology of CH (55%). Unstimulated serum thyroglobulin and ultrasound neck were used for etiological classification and subsequent genetic testing based on this classification. Using this approach, genetic mutations were detected in 38.46% (TDH – 40.9%, TD – 35.29%). DUOXA2 and TTF-2 were the most common mutations seen in individuals TDH and TD respectively.