Overview  

Organ malformations, including those affecting the kidneys, in Cri du Chat syndrome (CdCS) are not very common. However, in cases where they are present, they can be serious and sometimes life-threatening. This article discusses some kidney abnormalities that have been observed in some CdCS patients and the impact they can have on health.

What is cri du chat syndrome?

Cri du Chat syndrome (CdCS), translating literally from French to English to ‘Cry of the Cat’, is a rare genetic disorder observed in 1 in 15,000 to 1 in 50,000 live births. It is a result of a deletion on chromosome 5 and is characterised by a high-pitched, cat-like cry. It is associated with many complications, including organ defects, scoliosis and intellectual disability.¹ 

Causes

Humans have 22 pairs of chromosomes and a 23rd pair of sex chromosomes. As a structure, each chromosome presents a short arm and a long arm. Approximately 80% of Cri du Chat cases are caused by a de novo (not seen in previous generations, according to the National Cancer Institute) partial or complete deletion on the short arm of chromosome 5; only around 10% of cases are associated with a parental translocation.² 

Symptoms

According to the National Organisation for Rare Disorders (NORD), in infants with CdCS, the most distinctive symptom is the high-pitched, shrill cry, which usually becomes less pronounced after the first few weeks of life. 

Other symptoms include:

• Low birth weight
• Hypotonia (low muscle tone)
• Microcephaly (an abnormally small head)
• Distinctive facial features, such as an abnormally round face (moon face), broad nasal bridge, widely spaced eyes, low-set ears

Long term effects

As a result of hypotonia, many infants with CdCS may experience feeding difficulties and gastro-oesophageal reflux diseases (GORD). As they grow older, most will also show some degree of psychomotor or intellectual disability. Stunted growth and speech delay are also often observed. Renal (kidney-associated) complications are seen in about 5.5% of CdCS cases.³ 

Treatment

While there is no specific treatment for CdCS itself, patients may undergo physiotherapy and speech therapy to help manage any psychomotor or intellectual disabilities. Patients may also receive treatment for complications associated with CdCS, such as organ malformations.

Diagnosis

Diagnosis of CdCS is usually based on symptoms present at birth, however, a definitive diagnosis can be given before birth using genetic testing, such as a technique called amniocentesis. This is a prenatal examination indicated in the first trimester of pregnancy and involves collecting and analysing a sample of the amniotic fluid. Other methods of genetic testing can be carried out, such as karyotype analysis, fluorescence in situ hybridisation (FISH) testing and chromosome microarray analysis.

Prognosis

Around 75% of deaths associated with CdCS occur in the early months of life, and 90% during the first year. The size and location of the deletion on chromosome 5 have a large influence on the prognosis of each individual patient. Early diagnosis also greatly improves prognosis, as therapeutic measures can be implemented earlier to help with social adaptation and improvement of physical and psychomotor development.² 

Kidney abnormalities in cri du chat syndrome

The main function of the kidneys is to filter and remove waste products from your blood to be excreted in the urine. Kidney abnormalities can lead to an increased risk of contracting urinary tract infections (UTIs) or kidney failure. Although rare, some kidney malformations have been observed in CdCS patients.⁴

Horseshoe kidney

Most humans have two kidneys and each one is located on either side of the spine. Horseshoe kidney refers to the fusion of the kidneys at the base, forming a ‘U’, or a horseshoe shape. It is the most common fusion defect of the kidneys, occurring in about 0.25% of the population. Around 7 out of 10 patients with horseshoe kidneys experience symptoms, such as abdominal pain, nausea, kidney stones and urinary tract infections (UTIs). Those with a horseshoe kidney are more likely to experience vesicoureteral reflux (VUR), where the urine flows backwards from the bladder into the ureter (the tube connecting the kidney to the bladder). This can allow bacteria to grow easier in the urinary tract, which causes a UTI.⁵

Renal ectopia

An ectopic kidney is a kidney which is not found in its normal position. Renal ectopia refers specifically to a kidney which is on the opposite side of the body i.e. both kidneys are on the same side. Most people with an ectopic kidney don’t experience any symptoms or health complications and it can remain undetected. Ectopic kidneys are usually found during a foetal ultrasound or medical tests to find the cause of abdominal pain or to check for UTIs. Similarly to those with a horseshoe kidney, people with an ectopic kidney are at a higher risk of experiencing VUR.

Hydronephrosis

Hydronephrosis is caused by a build-up of urine inside the kidneys, causing them to become swollen. If detected and resolved quickly, it usually leaves no lasting damage, however, if it goes untreated for a long period of time, it can lead to irreversible effects such as kidney scarring and eventually kidney failure. It is more difficult to detect in infants, as they usually present asymptomatic, however, they may experience frequent UTIs. Symptoms include pain in the lower abdomen, difficulty urinating or a weak urine stream. The most common complications associated with hydronephrosis are UTIs and kidney infections.⁶ 

Incidences of kidney abnormalities in Cri du Chat patients

A study found that out of 185 patients with CdCS, 14 had some form of renal malformation, two of which were horseshoe kidney, three had renal ectopia and three had hydronephrosis. Other noted kidney conditions included kidney hypoplasia (at least one abnormally small kidney) and unilateral (one) kidney instead of two.

Summary

Cri du chat syndrome (CdCS) is a rare genetic disorder, which is caused by a partial or complete deletion on the short arm of chromosome 5. It is characterised by a high-pitched, wailing cry which resembles that of a cat. Other symptoms include a low birth weight, low muscle tone, microcephaly, widely spaced eyes or low-set ears. CdCS has a poor prognosis, with only 10% of infants surviving for longer than a year, but those that do survive are likely to experience many complications in later life, such as psychomotor or intellectual disability, stunted growth, or abnormalities in vital organs such as the kidneys. Common kidney abnormalities observed in CdCS patients include horseshoe kidney, renal ectopia and hydronephrosis. 

While there is no treatment available for CdCS itself, genetic testing can be carried out to diagnose it before birth, and there is treatment available for many complications associated with CdCS, such as kidney abnormalities.