Role of Next Generation Sequencing in the Etiological Diagnosis of Permanent Congenital Hypothyroidism With in Situ Thyroid

The primary aim of this study is to assess by NGS sequencing of a panel of target genes, the frequency and type of variants with potential pathogenic significance in a patient population with congenital hypothyroidism and in situ thyroid, born between January 2003 and December 2023 identified through Neontal Screening at the Regional Centre for Neonatal Screening for Endrocrine-Metabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

The secondary aims are to identify possible associations between genotype and phenotype; assess the risk of familial recurrence by searching for specific familial mutations; estimate the frequency of congenital hypothyroidisms with thyroid in situ out of the total number of congenital hypothyroidisms at the time of diagnostic confirmation; estimate the percentage frequency of transient and permanent congenital hypothyroidisms in patients with a thyroid in situ at diagnostic re-evaluation; identify possible prognostic factors for transient or permanent congenital hypothyroidism.

The retrospective phase of the study consists of the collection and analysis of clinical, hormonal and instrumental data of the cohort of patients enrolled by consulting their clinical records. More in detail, data on complete medical history, family history, physical examination with evaluation of major associated malformations, and thyroid ecography will be retrospectively collected.

Among this cohort, patients who have been diagnosed with permanent congenital hypothyroidism following diagnostic re-evaluation, according to clinical practice, will undergo molecular analysis by NGS sequencing of a panel of target genes for thyroid pathology.

Inclusion criteria

• Patients born in Emilia-Romagna region, Italy, between January 2003 and December 2023;
• Patients screened at the Regional Neonatal Screening Centre for Endrocrine-Metabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy, and recalled for suspected congenital hypothyroidism;
• Confirmed diagnosis of congenital hypothyroidism and in situ thyroid;
• Hormonal and clinical follow-up of at least 36 months at Centre for Endrocrine-Metabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy;
• Obtaining informed consent from parents/legal guardians of paediatric patients.

Exclusion criteria

• Patients with hypothyroidism associated with chromosomal syndromes.