The endocrine system is a complex network of glands that work together. A problem in one gland can affect others, making it challenging to pinpoint the issue. Traditional hormone tests can sometimes indicate abnormalities but fail to confirm a diagnosis. Here’s where genetic testing for endocrine disorders becomes crucial.
These tests provide a clear genetic diagnosis of endocrine disorders, helping doctors create effective treatment plans. Additionally, it assists in understanding whether a condition is hereditary, guiding preventive care for family members.
Endocrine Genetics
What is Endocrine Genetics?
Endocrine Genetics focuses on the role of genetic mutations in disorders affecting the endocrine system, which regulates growth, metabolism, reproduction, and homeostasis through hormone secretion. Advances in genetic testing have transformed the understanding and management of endocrine disorders, offering healthcare providers a reliable diagnostic tool, especially when traditional hormone tests yield inconclusive results. MedGenome’s genetic testing for endocrine disorders helps identify hereditary components of endocrine diseases to confirm diagnoses and assess familial risks. Early genetic diagnosis of endocrine disorders can significantly improve a patient's prognosis.
Common Genetic Endocrine Disorders
| Congenital Hypothyroidism | Congenital hypothyroidism is the partial or complete loss of thyroid gland function present at birth. Thyroid dysgenesis, a common cause of congenital hypothyroidism, is seen in 80–85% of cases. Dyshormonogenesis accounts for the remaining cases. | If untreated, congenital hypothyroidism can lead to intellectual disability and slow growth Inheritance could be autosomal recessive or dominant. | The disorder can be syndromic (such as Pendred syndrome or brain-lung-thyroid syndrome) or nonsyndromic. |
| Obesity | Genetic factors are estimated to contribute 40% to 70% to the risk of developing obesity. | Monogenic obesity refers to severe early-onset obesity, associated with endocrine disorders, mainly due to mutations in obesogenic or leptogenic genes (LEP, LEPR, POMC, PC1, MC4R). | Syndromic obesity occurs as part of broader genetic syndromes, including Prader–Willi syndrome and Bardet–Biedl syndrome. |
| Diabetes | Diabetes mellitus is an etiologically heterogeneous metabolic disorder. Type 1 and Type 2 diabetes are multifactorial and polygenic in nature. However, certain forms of diabetes are monogenic, caused by mutations in single genes affecting pancreatic β-cell development or function. The two major forms of monogenic diabetes include: Maturity-Onset Diabetes of the Young (MODY) and Neonatal diabetes mellitus. | MODY is a monogenic form of diabetes characterized by a primary defect in pancreatic β-cell function. Key features include: Early onset-typically in adolescence or early adulthood, autosomal dominant inheritance and preserved insulin production. Because of its clinical overlap, MODY is frequently misdiagnosed as Type 1 or Type 2 diabetes, leading to suboptimal management. Accurate genetic testing enables correct diagnosis and personalized treatment strategies. | Neonatal diabetes is predominantly monogenic and is usually diagnosed in children under 6 months of age. The fraction of cases of this disorder without a known cause is diminishing rapidly as new genes are discovered. The phenotype of this condition encapsulates numerous subtypes, wherein most etiologies involve a severe disruption in the ß-cell function. Transient neonatal diabetes may improve spontaneously but often relapses later in childhood or adolescence. Early genetic diagnosis plays a crucial role in guiding treatment—including identifying cases responsive to oral sulfonylureas instead of insulin. |
| Congenital Adrenal Hyperplasia (CAH) | Congenital Adrenal Hyperplasia (CAH) is the most common type of Disorder of Sex Development (DSD). It represents a group of autosomal recessive disorders caused by impaired synthesis of cortisol from cholesterol in the adrenal cortex. | Genetic Testing Strategy: The CYP21A2 gene is the primary gene implicated in 21-OHD CAH. Genetic testing generally follows a two-step approach: Amplicon based Sequence analysis of CYP21A2 – performed first. This identifies pathogenic variants in ~70–80% of affected individuals. | Gene-targeted deletion/duplication analysis – performed when one or no pathogenic variants are found by sequencing. Around 20–30% of cases require this step. Because CYP21A2 has a highly homologous pseudogene (CYP21A1P), there is a risk of diagnostic error. |
| Androgen Receptor Deficiency | Androgen receptor deficiency is the second most common Disorder of Sex Development (DSD) after congenital adrenal hyperplasia. The gene encoding the androgen receptor (AR) is located on the X chromosome. Pathogenic variants in the AR gene cause Androgen Insensitivity Syndrome (AIS), previously referred to as Testicular Feminization Syndrome (TFM). | The androgen insensitivity syndrome is an X-linked recessive disorder in which affected males have female external genitalia, female breast development, blind vagina, absent uterus, and female adnexa and abdominal or inguinal testes, despite a normal male 46, XY karyotype. Partial androgen insensitivity results in hypospadias and micropenis with gynecomastia (Reifenstein syndrome). | Next-generation sequencing (NGS) can detect approximately 95–97% of pathogenic variants associated with AIS. When no pathogenic AR variant is identified through sequencing (3–5% of cases), gene-targeted deletion/duplication testing for multi-exon or whole-gene deletions/duplications may be considered. MedGenome offers MLPA-based analysis for AR gene deletion/duplication testing as well as NGS-based sequencing for comprehensive AR gene evaluation. |
| Kallmann Syndrome | Kallmann syndrome can be characterized by delayed or absent puberty and an impaired sense of smell (hyposmia) or completely absent sense of smell (anosmia). | This feature distinguishes Kallmann syndrome from most other forms of hypogonadotropic hypogonadism, which do not affect the sense of smell. | Many people with Kallmann syndrome are not aware that they are unable to detect odors discovered through testing. |
| Familial Lipid Disorders | Patients with lipid disorders have trouble maintaining normal levels of body fat. These disorders can be found in several conditions such as metabolic syndrome, Polycystic Ovary Syndrome (PCOS), and obesity which require special management. | Special diets, exercise, and medications may be prescribed to manage hyperlipidemia and other lipid disorders. | A familial lipid disorder is a condition that causes very high levels of cholesterol. This condition can lead to early-onset Coronary Artery Disease (CAD). |
Clinical Applications of Endocrine Genetic Testing
Healthcare providers should consider recommending genetic testing for endocrine disorders in the following scenarios:
- Ambiguous Symptoms: When patients present with symptoms like ambiguous genitalia or dysgenic gonads, which may indicate underlying genetic conditions.
- Growth Concerns: For individuals with short stature or other growth abnormalities linked to potential endocrine dysfunctions.
- Obesity with Developmental Delays: When obesity is accompanied by developmental delays, suggesting a possible genetic basis.
- Family History of Hyperglycemia: In cases of hyperglycemia, a strong family history that points to inherited endocrine or metabolic disorders.
- Unexplained Hormonal Issues: For patients whose biochemical hormonal levels are inconclusive but show signs of endocrine imbalance.
Specifications
- Methodologies Next-generation Sequencing (NGS), Multiplex Ligation-dependent Probe Amplifi.cation (MLPA)
- Sample Required Peripheral blood: Minimum 3 ml; DNA: Minimum 1 microgram (50–100 ng/µl); CVS: 300–500 mg; amniotic fluid: 15–20 ml or T25 culture flask (100% confluency); dried blood spots (FTA cards): Five full blood spots; POC: Fresh placental or fetal tissue (minimum 5 mg) in transport media or sterile saline.
- Extracted DNA samples 1µg high-quality DNA.
- Turn Around Time (TAT) NGS: 19 working days.
- MLPA: 14 working days.
Endocrine Genetics Tests Offered by MedGenome
Endocrine Genetics – Single Gene Analysis
Test code - MGM392: Alstrom Syndrome (ALMS1) gene analysis
Test code - MGM027: Androgen receptor (AR) gene analysis
Test code - MGM028: Congenital adrenal hyperplasia CYP21A2 (21-0H) gene analysis
Test code - MGM452: Leptin deficiency (LEP) gene analysis
Endocrine Genetics – Multi-Gene Panels
Test code - MGM031: Congenital hypopituitarism gene panel
Test code - MGM309: Hereditary pancreatitis gene panel
Test code - MGM085: Hypercholesterolemia gene panel
Test code - MGM032: Kallmann syndrome gene panel
Test code - MGM033: Maturity-Onset Diabetes of the Young (MODY) & neonatal diabetes gene panel
Test code - MGM501: Monogenic and syndromic obesity gene panel
Other Test Details
Test code - MGM449: Prader-Willi/Angelman syndrome
Test code MGM435: Beckwith-Wiedemann /RussellSilver syndrome Methylationspecific deletion/duplication analysis
Key Highlights of MedGenome's Endocrine Genetics Test
High Throughput Analysis
Capable of analysing multiple samples simultaneously for efficiency.
High Sensitivity and Specificity
Ensures detection of relevant genetic changes with minimal false positives or negatives for trustworthy diagnostic outcomes.
Tailored Reporting for Clinicians
Detailed reports crafted to support clinical decisions, enhancing patient management and care planning.
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