Clinical characteristics of heterozygous HNF1B variants (MAGIC-LUCID)

Clinical characteristics of heterozygous HNF1B variants (MAGIC-LUCID)

Clinical feature	Evaluation and monitoring	Interventions
Congenital anomalies of the kidney and urinary tract (CAKUT)	Comprehensive metabolic panel, repeated annually Kidney ultrasound, repeat annually if cysts are present Uterine ultrasound when age-appropriate	Urology and pediatric nephrology referral, depending on anomalies Urology or gynecology referral for uterine anomalies
Chronic kidney disease with a bland urinary sediment	Estimated GFR, repeated annually or more frequently if decreasing	ACE inhibitor or ARB for hypertension Avoid nephrotoxic medications
Maturity onset diabetes of youth (MODY) type 5	Hemoglobin A1C, repeated annually	Oral therapy such as a sulfonylurea may be used initially Insulin may be required with disease progression Standard diabetes care
Hypomagnesemia	Serum magnesium level, repeated annually If hypomagnesemia is present, baseline ECG to evaluate QTc	Magnesium supplementation as needed
Hyperuricemia and gout	Serum urate level, repeated annually Clinical evaluation for gout as needed	Allopurinol for secondary prevention if gout develops
Increased LFTs	LFTs, repeated annually If LFTs are elevated, abdominal US for liver imaging	No intervention needed

Individuals with a germline pathogenic variant in HNF1B may have a number of clinical features that determine interventions and monitoring. Penetrance (likelihood of manifestations) and expressivity (constellation of manifestations) are variable, even within the same family. The mnemonic MAGIC-LUCID illustrates these features.^[1]

Magnesium – Hypomagnesemia due to magnesium leak in the kidney
Autosomal dominant
Genitourinary tract – Abnormalities such as bicornuate uterus
Inherited
CAKUT – Congenital anomalies of the urinary tract, including cystic kidneys, solitary kidney, hypoplastic kidney, bicornate uterus
Liver test abnormalities – Mild, asymptomatic elevations of AST, ALT, and alkaline phosphatase
Uric acid elevation – Gout may develop in young adulthood
Chronic kidney disease – Variable rate of progression, with some individuals developing end-stage kidney disease
Incomplete penetrance – Some or none of the clinical features may be present in affected family members
Diabetes – Maturity Onset Diabetes of Youth (MODY) type 5

Individuals with 17q12 deletion syndrome have additional abnormalities as described in UpToDate.

GFR: glomerular filtration rate; ACE: angiotensin converting enzyme; ARB: angiotensin II receptor blocker; ECG: electrocardiogram; QTc: corrected QT interval; LFTs: liver function tests; US: ultrasound; AST: aspartate aminotransferase; ALT: alanine aminotransferase.

Source:

The MAGIC-LUCID mnemonic is reprinted by permission from Springer: Pediatric Nephrology. Bleyer AJ, Wolf MT, Kidd KO et al. Autosomal dominant tubulointerstitial kidney disease: more than just HNF1b. Pediatr Nephrol 2021. https://www.springer.com/journal/467.

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Clinical characteristics of heterozygous HNF1B variants (MAGIC-LUCID)