Penetrance

17q12 recurrent deletion syndrome is highly penetrant. Although it is inherited about 25% of the time, there have been no clear reports of unaffected parents with 17q12 recurrent deletion syndrome.

Source: GeneReviews — "17q12 Recurrent Deletion Syndrome"

Diagnostic Criteria

No consensus clinical diagnostic criteria for 17q12 recurrent deletion syndrome have been published.

Suggestive Findings

17q12 recurrent deletion syndrome should be suspected in individuals with any of the following clinical, laboratory, and family history findings.

Clinical findings

• Kidney abnormalities

Source: GeneReviews — "17q12 Recurrent Deletion Syndrome"

Differential Diagnosis

Kidney structural or functional defects. See .

Table 3.

Genetic Disorders with Kidney Structural or Functional Defects in the Differential Diagnosis of 17q12 Recurrent Deletion Syndrome

Gene(s) | Disorder | MOI | Kidney-Related Phenotype | Other Features

20 genes incl:CEP290INVSIQCB1NPHP1NPHP3NPHP4TMEM67 | Nephronophthisis-related ciliopathies | AR(typically) | • Polyuria polydipsia resulting from urine-concentrating ability

• Chronic tubulointerstitial nephritis

• Progression to ESKD

• Note: NPH is suspected in absence of CAKUT signs/symptoms of glomerular kidney disease.

| • Chronic anemia resistant to therapy

Source: GeneReviews — "17q12 Recurrent Deletion Syndrome"

Management Guidelines

No clinical practice guidelines for 17q12 recurrent deletion syndrome have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with 17q12 recurrent deletion syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

17q12 Recurrent Deletion Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Kidney structural or functional defects

| • Blood pressure

• Kidney bladder ultrasound

• Serum BUN, creatinine, electrolytes (incl calcium, Mg, phosphorus) uric acid

• Urine protein, Mg, creatinine

• Consultation w/nephrologist

| • Random urine Mg/creatinine is needed to calculate fractional excretion of Mg.

• FEMg (2%) is diagnostic of tubular Mg wasting in those w/normal kidney function.

Neurodevelopmental/neuropsychiatric disorders

| • Assessment of speech language

• Cognitive, motor, social development

• Perceptual anomalies

• Mood

• Behavior

|

MODY5

| • Fasting glucose hemoglobin A1c levels

• Consultation w/endocrinologist

|

Genital tract abnormalities

| • Males: clinical exam

• Females: pelvic ultrasound gynecologic exam to evaluate for possible mllerian abnormalities

|

Liver abnormalities

| Liver function tests (hepatic function panel, GGT), lipid panel |

Hyperparathyroidism

| • ...

Source: GeneReviews — "17q12 Recurrent Deletion Syndrome"

Clinical Guidance

Individuals with HNF1B-associated kidney disease (including the 17q12 recurrent deletion) who develop end-stage kidney disease (ESKD) and require kidney transplantation are at increased risk for developing post-transplant diabetes mellitus; therefore, use of an immunosuppressive regimen that avoids tacrolimus and mammalian target of rapamycin (mTOR) inhibitors and reduces corticosteroid exposure may be beneficial, including for those who do not have preexisting diabetes . Nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be avoided by those with kidney abnormalities. Hepatotoxic medications and alcohol should be avoided by those with liver abnormalities. For individuals with mental health conditions such as autism spectrum disorder, schizophrenia, or bipolar disorder, the authors recommend caution when considering the use of antipsychotic agents that may lead to weight gain and increased risk of metabolic syndrome and diabetes mellitus, since individuals with 17q12 deletions are already at increased risk for diabetes mellitus. Likewise, the use of mood stabilizers that can affect kidney function in the long term, such as lithium, should be carefully considered in the setting of potential underlying anatomic and functional abnormalities in individuals with 17q12 deletions.

Source: GeneReviews — "17q12 Recurrent Deletion Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "17q12 Recurrent Deletion Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 6.

17q12 Recurrent Deletion Syndrome: Recommended Surveillance

System/Concern | Evaluation | Frequency

Kidney structure/function

| Kidney bladder ultrasound to monitor for kidney cysts or other structural abnormalities | • In those w/o known structural defects: 12 mos after establishing diagnosis, then every 2-3 yrs in childhood/adolescence every 3-5 yrs in adulthood

• If an abnormality is detected, more frequent ultrasound may be warranted.

Monitor:

• Blood pressure

• Kidney function

• Serum concentration of Mg, potassium, uric acid

• Urine Mg creatinine

• Urine protein-to-creatinine ratio

| • Periodic, preferably under guidance of nephrologist

• Annual or more frequent monitoring may be advised for those who: (1) have lab findings suggestive of kidney disease; (2) are taking potentially nephrotoxic medications (e.g., NSAIDs); (3) have genitourinary structural abnormalities.1

Development / neurobehavioral / psychiatric

| Assess developmental progress educational needs. | At each visit throughout childhood adolescence

Assess for features of ASD ADHD. | At each visit in early childhood

Full psychoeducational eval incl assessment of speech, cognitive, social/emotional, adaptive, motor skills | In children who experience difficulty w/school or behavioral challenges

Assess for prodromal psychotic symptoms bipolar disorder.

Source: GeneReviews — "17q12 Recurrent Deletion Syndrome"