Thread by @SwastiThinks

Have you ever wondered when we should pursue genetic testing in paediatric patients with cystic kidneys?#nephtwitter #medtwitter #NephMadness #Genetics. But first a quick primer on paediatric genetic kidney cystic diseases😃😃

Paediatric genetic cystic kidneys are heterogenous group of disorders. The age of presentation, clinical features and family history are often useful for coming to a diagnosis. linkinghub.elsevier.com/retrieve/pii/S…

But first let's talk about 4 common genetic causes of cystic kidney disease in children:
🌟ADPKD
🌟 ARPKD
🌟Nephronophthisis
🌟 HNF-Beta related disease

ADPKD is the commonest genetic cystic kidney disease 🌟Incidence of 1:500 to 1:1000
🌟Presents mostly in the 4th decade of life
🌟Caused by mutations in polycystin 1, 2 (PKD 1, PKD 2) and rarely GANAB gene
nejm.org/doi/full/10.10…
ncbi.nlm.nih.gov/pubmed/27259053

Though ADPKD typically presents in adults, it has been diagnosed in utero, in infants, children and adolescents. Most children are asymptomatic but can present with hypertension or gross haematuria ncbi.nlm.nih.gov/pmc/articles/P…

Which person with ADPKD needs genetic testing?
1) 5 yrs old, No symptoms, strong family Hx of ADPKD
2) 1 yr old, Bilat large renal cysts, hypertension & no family Hx
3) 18 year old with family Hx , wants to donate kidneys to his relative with ESKD

7/ One instance where genetic testing is useful is a child with phenotypically aggressive ADPKD and no family history

Another situation where genetic testing is useful is:
•Young person with strong family history of ADPKD
•Who is now considering living related donation to a relative with ESKD
•Because we know that renal ultrasound may not show cysts in young people ncbi.nlm.nih.gov/pmc/articles/P…

Most experts do not recommend genetic testing in asymptomatic children with family history of ADPKD as:
•It may cause undue anxiety
•May lead to loss of insurance
•Furthermore, there is no specific treatment approved in children yet.
ncbi.nlm.nih.gov/pmc/articles/P…

Parents with ADPKD however should be counselled on:
•How ADPKD is inherited
•Risks/benefits of testing
•Diagnostic screening with ultrasound or annual BP and proteinuria check can be offered
•At-risk children should be made aware of their risk once they are adults

What about ARPKD?
•Caused by mutation in PKHD1 and DZIP1L gene
•Mostly presents as neonate or even in utero as bilateral enlarged echogenic kidneys and oligohydramnios
•Can present at birth with potter’s sequence
pubs.rsna.org/doi/pdf/10.114… ncbi.nlm.nih.gov/pmc/articles/P…

Routine genetic testing is not done in ARPKD if consistent clinical picture and is largely reserved for prenatal testing and pre-implantation genetic diagnosis
ackdjournal.org/article/S1548-…

A group of children where genetic testing may be useful include Nephronophthisis which is an autosomal recessive cystic kidney disease resulting from mutations in at least 13 different NPHP group of genes which encode proteins called nephrocystins

NPHP has a variable phenotype but is characterized by:
•Small to normal size kidneys
•Corticomedullary cysts
•Urinary concentrating defects
•Polyuria, polydipsia
•Bland Urine
•Growth retardation
•Anaemia
•Progressive kidney disease
ncbi.nlm.nih.gov/pmc/articles/P…

There are multiple extrarenal manifestations of NPHP and it can also be part of rare syndromes such as Bardet-Biedl syndrome and Joubert syndrome.
ncbi.nlm.nih.gov/pmc/articles/P…

Another interesting cystic kidney disease is HNF beta gene related disease which can present with:
•Renal cysts
•Early onset diabetes mellitus
•Hypomagnesemia
•Intellectual disability and autism
ncbi.nlm.nih.gov/pmc/articles/P…

Besides this, some syndromes can also be associated with cysts in kidney and it's important to recognise them and provide appropriate genetic counselling. Which syndrome/s can be associated with cysts in kidney?

So now we know that some cystic kidney disease in infancy may lead to progressive CKD and ESKD in childhood, whereas others may be static. So, who should be offered genetic testing? Here' is my summary:

Another thing to keep in mind is that these recommendations will change when testing becomes more readily available and specific treatments are available for paediatric patients
frontiersin.org/articles/10.33…

I want to leave you with interesting information so you can read more on this. It has been recognised that ADPKD, ARPKD and many genetic cystic kidney diseases including nephronopthisis are ciliopathies. ncbi.nlm.nih.gov/pubmed/21506742