CoGenesis® Endocrine

CoGenesis® Endocrine is a comprehensive next-generation sequencing (NGS) panel that analyses 436 genes across 14 endocrine disease categories. Rather than testing a single gene or a narrow condition-specific panel, this panel is particularly suited to patients who have already undergone standard investigations without a clear diagnosis.

The endocrine system is governed by an intricate web of genes that regulates metabolism, growth, reproduction, and stress response. Disruption to the endocrine system can produce a wide spectrum of clinical presentations, from subtle childhood growth failure to life-threatening adrenal crises. Individually rare, these disorders are collectively common enough that a significant proportion of patients with unexplained endocrine dysfunction will have an identifiable genetic cause.

Thyroid disorders: Genes responsible for thyroid gland development (PAX8, NKX2-1, FOXE1), thyroid hormone synthesis (TPO, TG, DUOX2, SLC5A5), thyroid hormone transport (SLC16A2, SLC26A4), and thyroid hormone receptor function (THRA, THRB).

Adrenal disorders: Steroidogenesis genes (CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, STAR) for congenital adrenal hyperplasia, plus adrenal development genes (NR0B1, MC2R, MRAP, NNT, AAAS) covering adrenal hypoplasia, glucocorticoid resistance, and Triple-A syndrome.

Pituitary and growth axis: GH1, GHRHR, GHR, IGF1, IGF1R, PAPPA2, and pituitary transcription factors (POU1F1, PROP1, HESX1, LHX3, LHX4) underlying combined or isolated pituitary hormone deficiencies and growth hormone insensitivity syndromes.

Disorders of sex development (DSD): Gonadal determination and steroidogenesis genes (SRY, NR5A1, WT1, DMRT1, DHH, MAP3K1) alongside androgen receptor and gonadotropin signalling genes (AR, FSHR, LHCGR, AMH, AMHR2).

Monogenic diabetes and hyperinsulinism: MODY genes (HNF1A, HNF1B, HNF4A, GCK, PDX1, NEUROD1), neonatal diabetes genes (ABCC8, KCNJ11, INS, EIF2AK3), congenital hyperinsulinism (GLUD1, HADH), and syndromic diabetes (WFS1, GLIS3).

Hypogonadotropic hypogonadism and Kallmann syndrome: ANOS1, FGFR1, CHD7, GNRHR, KISS1R, PROK2, and over 15 additional HH-associated genes.

Genetic obesity and melanocortin pathway: LEP, LEPR, MC4R, POMC, PCSK1, and related genes underlying severe early-onset obesity.

Lipodystrophy: AGPAT2, BSCL2, LMNA, CAV1, CAVIN1, and related genes for congenital and familial partial lipodystrophy syndromes.

Primary ovarian insufficiency (POI): Meiotic and DNA repair genes (STAG3, MCM8, MCM9, MSH5, HFM1, BMP15, FIGLA, FOXL2) alongside FMR1 for premature ovarian failure.

1. Children and adults with rare or clinically complex endocrine presentations where standard biochemical evaluation is inconclusive, including congenital hypothyroidism, resistance to thyroid hormone, thyroid dyshormonogenesis, or adrenal insufficiency of unclear cause.
2. Disorders of sex development (DSD) or ambiguous genitalia requiring molecular characterisation of gonadal determination, steroidogenesis, or hormone receptor pathways.
3. Neonatal or early-onset diabetes mellitus, persistent congenital hyperinsulinism, or suspected maturity-onset diabetes of the young (MODY), where a monogenic aetiology would change clinical management (e.g., sulphonylurea eligibility in ABCC8/KCNJ11 neonatal diabetes).
4. Hypogonadotropic hypogonadism, Kallmann syndrome, or primary ovarian insufficiency in the reproductive-age population where a genetic cause is suspected but unconfirmed.
5. Genetic obesity due to melanocortin pathway defects or leptin/leptin receptor deficiency, or syndromic endocrine conditions including lipodystrophy syndromes, Bardet-Biedl syndrome, and Alstrom syndrome.

14 sub-panels included:

4mL Peripheral blood (EDTA), 2mL saliva, or buccal swab

Preferred sample type:

• 4mL Blood (EDTA tube),
• Codex-provided buccal swabs (4 swabs)
• Codex-provided saliva collection kit (2mL)

Saliva or buccal swab sample collection: Follow the enclosed instructions; do not eat, drink, or smoke for 30 minutes before collection.

• Results may identify pathogenic, likely pathogenic, or variants of uncertain significance (VUS).
• Positive findings can inform risk‑reducing strategies and treatment options.
• Genetic counseling is recommended to help families understand implications.

Rare endocrine disorders are individually uncommon but collectively represent a significant diagnostic challenge across paediatric and adult endocrinology. Individually, their prevalence ranges from approximately 1 in 10,000 (congenital adrenal hyperplasia due to CYP21A2) to 1 in 100,000 or rarer. A significant proportion of patients with unexplained endocrine dysfunction carry a pathogenic variant in a defined gene, and the route to diagnosis is frequently a years-long diagnostic odyssey through biochemical tests, imaging, and sequential single-gene testing.

The endocrine system is genetically complex: over 400 distinct genes govern hormone synthesis, secretion, transport, receptor signalling, and feedback regulation. Most rare endocrine disorders follow Mendelian inheritance — autosomal dominant, autosomal recessive, or X-linked. In paediatric cohorts with congenital hypothyroidism, pathogenic variants are identified in 15–25% of cases; for combined pituitary hormone deficiency, published cohorts report a genetic diagnosis in 20–40% using multi-gene panels; and for Kallmann syndrome/hypogonadotropic hypogonadism, broad panel sequencing identifies a cause in 30–50% of cases.

Monogenic diabetes is estimated to account for 1–5% of all diabetes cases but is substantially under-diagnosed. MODY (primarily HNF1A and GCK subtypes) and neonatal diabetes (ABCC8/KCNJ11) have directly actionable genetic findings: sulphonylurea therapy is highly effective in ABCC8/KCNJ11 neonatal diabetes and HNF1A-MODY, frequently eliminating insulin dependence. Congenital adrenal hyperplasia (CAH) due to CYP21A2 mutations affects approximately 1 in 15,000 newborns globally; genotype influences phenotype (classic salt-wasting vs. non-classic), and molecular confirmation guides treatment planning and newborn screening cascade.

Disorders of sex development (DSD) represent one of the most genetically and clinically complex endocrine categories, with molecular aetiology spanning over 30 genes across gonadal determination, androgen biosynthesis, gonadotropin signalling, and sex hormone receptor pathways. A molecular diagnosis changes surgical planning, hormone replacement strategy, gonadal surveillance requirements, fertility counselling, and reproductive planning for affected individuals and their families.

The breadth of the CoGenesis Endocrine panel reflects the phenotypic and genetic overlap between endocrine syndromes, and addresses the clinical reality that the same presentation (e.g., primary amenorrhoea, short stature, neonatal hypoglycaemia) can arise from variants in dozens of different genes.