Monogenic diabetes and family health: Why genetic testing matters

Monogenic diabetes (caused by a change in a single gene) affects around 3.6 per cent of those diagnosed below the age of 25 years. Genetic testing matters as ensuring the correct diagnosis impacts on treatment, recognition of associated features and follow up of family members. Around 80 per cent of cases of monogenic diabetes are initially misdiagnosed often as having Type 1 diabetes due to the young age of diagnosis. Identifying likely causes and referring for genetic testing is crucial to identify the specific gene affected as different genes have very different treatment requirements, clinical characteristics and prognosis.

Types of Monogenic diabetes

Monogenic diabetes can be broadly separated into three groups - neonatal diabetes diagnosed within six months of life; diabetes diagnosed below 25 years of age in an individual usually with an affected parent or child, often described as MODY (Maturity Onset Diabetes of the Young); young onset diabetes associated with other syndromic features.

A majority of monogenic diabetes cases are characterised by an autosomal dominant inheritance where the diabetes is passed down from an affected parent to their child with each child at 50 per cent risk of inheriting the affected gene. Neonatal diabetes and around 50 per cent of cases of HNF1B MODY can occur ‘de-novo’ but in these cases when these individuals go on to have children, each will be at 50 per cent risk of inheriting the condition. In communities where consanguinity is common certain forms of neonatal diabetes can be inherited in an autosomal recessive manner. Identifying the gene affected enables appropriate genetic counselling for other family members.

Characteristics and treatment

Each type of monogenic diabetes has unique clinical characteristics and treatment requirements.

GCK MODY is characterised by a mild, stable hyperglycemia which needs no treatment or follow up outside pregnancy and is often detected in routine screening. HNF1A MODY is typically present in adolescence or young adulthood and can be best managed by tablets, but these individuals are at risk of myocardial infarction as their HDL (high density lipoprotein) is large and buoyant, and non-cardio-protective. HNF4A MODY presents in a similar way to HNF1A, and oral medication is an optimal treatment but in individuals who inherit this genetic change are at risk of macrosomia and neonatal hypoglycaemia which may require treatment.

HNF1B MODY is characterised by renal developmental disorders in addition to diabetes, and uterine abnormalities can also be a feature. This type typically requires insulin treatment due to the small pancreatic size along with pancreatic enzyme replacement treatment. Mitochondrially Inherited Diabetes and Deafness (MIDD) is maternally inherited and characterised by a bilateral sensorineural deafness which often precedes the diabetes, and insulin treatment is usually required within two years of diagnosis. The commonest causes of neonatal diabetes in non-consanguineous populations are mutations in the KATP channel genes and are best treated with high doses of oral medication. It may be associated with learning difficulties in some cases. In consanguineous populations, Wolcott Rallison syndrome is more common and it has a wide range of other features including liver dysfunction and skeletal dysplasia.

Genetic testing is indispensable for identifying monogenic diabetes and the specific gene mutations for it. It not only ensures the correct diagnosis but also plays a crucial role in tailoring treatment plans, recognising associated features, and providing genetic counselling for affected individuals and their families. By embracing genetic testing as a routine part of diabetes diagnosis, we can enhance family health management and offer the best possible care to those affected by this complex condition.

Why Genetic Testing for Monogenic Diabetes is Essential

 Monogenic diabetes affects 3.6 per cent of those under 25.

 80 per cent of cases are initially misdiagnosed, often as Type 1 diabetes.

 Identifying the specific gene is crucial for tailored treatment.

 Monogenic diabetes can be categorised into neonatal, MODY, and syndromic forms.

 Autosomal dominant inheritance is common, but de novo and recessive cases exist.

 Genetic testing enables appropriate family genetic counselling.

 Different monogenic forms have distinct clinical characteristics and treatment requirements.

 Early genetic testing can lead to better management and care.

 Families benefit from accurate diagnosis and proactive genetic counselling.

Article authored by Nurse Margaret Helen Shepherd, a distinguished winner of the 2nd edition of the Aster Guardians Global Nursing Award

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