Introduction

Polyhydramnios (hydramnios) is a medical condition in which excess amniotic fluid builds up during pregnancy; amniotic fluid is a liquid that surrounds the fetus and protects it from injuries and trauma.¹ It occurs in 1-2% of all pregnancies. It increases the risk of perinatal, maternal morbidity and mortality rate.² It is usually idiopathic; however, gestational diabetes, foetal abnormalities, and foetal infection have the potential to cause polyhydramnios.

It is diagnosed by ultrasound, maternal diagnostic testing and lab tests.¹ The complications of disease include preterm labour, rupture of membrane, umbilical cord prolapse, foetal macrosomia, and postpartum hemorrhage.² Treatment can be obtained in two ways: 1) amniocentesis (amnioreduction), 2) indomethacin (prostaglandin synthetase inhibitor). In addition, treatment of known causes is also necessary.¹

The term Fryns syndrome was first described by Fryns in 1979,³ It is an autosomal recessive congenital disorder. It is a rare but lethal syndrome characterised by diaphragmatic defects hernia), distinctive facial features, hypoplasia of lungs, polyhydramnios, small phalanges, eyes, cleft palate and lips, cardiac, renal, brain, gastrointestinal and urinary tract abnormalities.⁴ 

The life span of a patient is not beyond the neonatal age, and those who survive have to live with multiple abnormalities. The characteristic features, genetic testing, and family history are considered for diagnosis. Unfortunately, there is no treatment, but supportive treatment is provided to ease the patient's life, and genetic counselling is given to parents.⁵

The association between polyhydramnios and Fryns syndrome is that polyhydramnios is one of the significant markers of Fryns syndrome. However, the diagnosis is not confirmed with the presence of polyhydramnios because it is closely related to other diseases as well. Therefore, further evaluation might be needed.

Polyhydramnios

Pathophysiology

Under normal physiological conditions, there is a balance between the production and absorption of amniotic fluid. The maintenance of fluid volume depends upon foetal urination and liquid production from the lungs, and the reabsorption of fluid volume is obtained by foetal swallowing.⁶

The normal range of urine production is 500-1200 ml, and swallowing between 210-760 ml of fluid. Any disturbance in the amniotic fluid volume due to increased urination or disruption in foetal swallowing results in polyhydramnios.⁶

Causes

According to research, 17% of cases of mild polyhydramnios are due to an underlying cause, whereas in moderate to severe polyhydramnios, 91% of cases show an underlying cause. The most common etiologies of polyhydramnios include:⁶

• Genetic disorders and foetal abnormalities
• Gestational diabetes (diabetes during pregnancy)
• Multiple pregnancies
• Disturbance in foetal swallowing of amniotic fluid
• Viral infection
• Foetal anaemia
• Neuromuscular disorders⁶

Diagnosis

The most common diagnostic tool is ultrasound, it is used to assess the volume of amniotic fluid and foetal development, SDPV (single deep vertical pocket) used to evaluate amniotic fluid; the normal range of SDPV is 2-8 centimetre and AFI (amniotic fluid index) is used to assess the severity of disease; its normal range are 5-25 cm. Once the polyhydramnios is confirmed, further diagnostic tests should be performed to determine the underlying cause, for example, a maternal glucose test, a blood test for infection, or foetal anemia.²

Complications

The complications of polyhydramnios are associated with the severity of the disease; mild polyhydramnios has rare complications, in contrast to moderate or severe polyhydramnios, which have a high risk of complications. It includes:⁷

• Premature birth
• Abruption of membranes/ placental abruption (when the placenta is displaced from the wall of the uterus before childbirth)
• Possibility of C-section delivery.
• Breech pregnancy (when the baby’s position is bottom-down instead of head-down during pregnancy)
• Umbilical cord prolapse
• Difficulty in breathing 
• Risk of foetal death⁷

Fryns syndrome

Pathophysiology

The pathophysiology of Fryns syndrome is not clearly understood, but some research shows it is an autosomal recessive congenital disorder (it means an individual inherits two copies of defective genes from both parents). Variation of the PIGN gene, involved in the biosynthesis of glycosylphosphatidylinositol-GPI, causes Fryns syndrome. Mutation of PIGN causes multiple genetic disorders.⁵

Clinical features

The clinical features of Fryns syndrome include: 

• Congenital diaphragmatic hernia: This means the incomplete development of the diaphragm that results in abdominal parts moving towards the chest cavity⁸
• Hypoplasia: This means the lungs are underdeveloped⁵
• Distinctive facial features like cloudy cornea, cleft palate and lips, abnormal helices, wide mouth, and small jaw⁸
• Hypoplasia of nails, phalanges, hands, and thorax⁸
• Systemic abnormalities include cardiac issues, renal cysts, respiratory distress, nervous system abnormalities, and urogenital issues⁵

Diagnosis

The diagnosis is primarily based on two types of testing: clinical and molecular testing

Clinical testing

It includes 6 clinical features which need to be observed for diagnosis:

1. Diaphragmatic defect
2. Hypoplasia of lungs
3. Characteristics of facial features
4. Distal limb hypoplasia
5. Any characteristic feature that differs from normal (deformity)
6. Family history⁹

Molecular testing

Another diagnostic tool is molecular genetic testing to determine PIGN variants, including single and multi-gene testing.⁵

Association between polyhydramnios and Fryns syndrome

The association between polyhydramnios and Fryns syndrome is not clearly understood. However, some studies show that polyhydramnios is a characteristic associated anomaly in Fryns syndrome, and the following mechanisms show the relationship between both diseases.⁵ 

According to research, 76% of foetuses have Fryns syndrome in which polyhydramnios is a common sign; out of 76%, only 11% survived.¹¹

1. Imbalance between fluid absorption and swallowing

One of the clinical findings in Fryns syndrome is the occurrence of GI anomalies such as abnormal rotation of the intestine and herniation of abdominal organs, which further disrupts fluid absorption and swallowing. These are the major causes of polyhydramnios.⁵

2. Respiratory dysfunctions

If people with Fryns syndrome get respiratory dysfunction as a comorbidity, including herniation, which affects foetal ability to swallow amniotic fluid, resulting in accumulation of amniotic fluid during pregnancy.⁵

3. Other genetic deformities

Many congenital abnormalities involved in Fryns syndrome become the reason for polyhydramnios.⁵

Treatment and management of polyhydramnios and Fryns syndrome

Treatment of polyhydramnios

When a patient is diagnosed with polyhydramnios, further evaluation is mandatory to detect the other underlying causes. The treatment of polyhydramnios is basically to reduce the amniotic fluid volume to save the mother’s life and smooth pregnancy. Mild polyhydramnios does not require any treatment; it may go away on its own. Treatment of the underlying cause is also necessary because it helps get rid of polyhydramnios. Two methods are used for treatment includes:¹⁰

1. Amniocentesis: In this method, excess amniotic fluid drains from the uterus. The complications may arise during this procedure in 1-3% of cases, and they include a premature baby, rupture of the membrane and placenta¹⁰
2. Prostaglandin synthetase inhibitor: This is used to treat polyhydramnios, as it reduces contractions and the volume of amniotic fluid.¹⁰

Treatment of fryns syndrome

There is no cure for Fryns syndrome; however, anomalies may need consultation and proper treatment to improve the patient's quality of life. Neonates with diaphragmatic hernia are immediately sent for intubation to prevent the bowel’s herniation and inflammation. If a patient suffers from seizures, anti-seizure medications are used to treat them. Developmental services, like motor, feeding, adaptive, and language therapy, are also needed. Any particular abnormality should be discussed with specialists such as a paediatrician, cardiologist, urologist, or pulmonologist as per the patient’s needs.⁵

Monitoring and care

Patients with polyhydramnios need regular monitoring and care throughout pregnancy. Techniques like ultrasound are crucial to monitor foetal growth, amniotic fluid volume, foetal position, timing of delivery, and maternal health. Regularly perform lab tests or any test needed to check underlying conditions.⁶ Genetic counselling is also crucial for parents.⁵

FAQs

Q1 - What is he prognosis of Fryns syndrome?

Answer - Fryns syndrome is a life-threatening condition; survival beyond neonatal age is difficult, and those who survive have to live with abnormalities.

Q2 - What are the early signs of polyhydramnios?

Answer - Digestion issues, acidity, difficulty in breathing, constipation, swelling in hands/feet, and UT infections.

Summary

Polyhydramnios and Fryns syndrome are both rare but serious disorders. There is a close relationship between too much amniotic fluid during pregnancy and genetic abnormalities. Polyhydramnios is a significant marker resulting in Fryns syndrome, but there are some other underlying causes which interpret similar disorders. Therefore, it is essential to diagnose the condition before starting treatment. Along with medication, proper monitoring with care throughout the pregnancy is needed. Moreover, further studies and research are still going on to identify the connection between these two diseases.