Recurrent hydatidiform mole

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Recurrent hydatidiform mole is a condition that affects women and is characterized by the occurrence of at least two abnormal pregnancies that result in the formation of hydatidiform moles. A hydatidiform mole is a mass that forms early in pregnancy and is made up of cells from an abnormally developed embryo and placenta. Normally, the embryo would develop into a fetus and the placenta would grow to provide nutrients to the growing fetus. When a hydatidiform mole occurs once, it is known as sporadic hydatidiform mole; if it happens again, the condition is known as recurrent hydatidiform mole.

The first symptom of a hydatidiform mole is often vaginal bleeding in the first trimester of pregnancy. During an ultrasound examination, the abnormal placenta appears as numerous small sacs, often described as resembling a bunch of grapes.

Hydatidiform moles are not naturally discharged from the body and must be surgically removed, typically by the end of the first trimester. After removal, there is up to a 20 percent risk that any tissue left behind will continue to grow and become a cancerous (malignant) tumor called a persistent mole. If the tumor invades the surrounding tissue of the uterus, it is called an invasive mole. In rare cases, this malignant tumor can transform into a different form of cancer called gestational choriocarcinoma that can spread (metastasize) to other tissues such as the liver, lungs, or brain.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in multiple genes have been found to cause recurrent hydatidiform mole. About 55 percent of cases of this condition are caused by NLRP7 gene mutations and about 5 percent of cases are caused by KHDC3L gene mutations. Mutations in other genes each account for a small percentage of cases.

The proteins produced from the NLRP7 and KHDC3L genes are critical for normal egg cell (oocyte) development, which impacts embryonic development. Within oocytes, the exact role of NLRP7 and KHDC3L proteins are not known. However, they are thought to play a role in a phenomenon known as genomic imprinting. Through genomic imprinting certain genes are turned off (inactivated) based on which parent the copy of the gene came from. For most genes, both copies of the gene (one copy inherited from each parent) are active in all cells. However, for a small subset of genes, only one of the two copies is active and the other is turned off. For some of these genes, the copy from the father is normally active, while for others, the copy from the mother is normally active.

NLRP7 or KHDC3L gene mutations result in the production of proteins with impaired function. As a result, oocytes do not develop normally. A pregnancy that results from an abnormal oocyte cannot develop properly, resulting in recurrent hydatidiform mole. NLRP7 or KHDC3L gene mutations can also prevent proper imprinting of multiple genes that contribute to a developing embryo, leading to abnormal gene activity (expression). It is not clear if problems with imprinting also contribute to the development of a hydatidiform mole. In women with NLRP7 or KHDC3L gene mutations, a hydatidiform mole will develop in every pregnancy that occurs with her egg cells.

A small number of cases of recurrent hydatidiform mole have been found to be caused by mutations in genes that play important roles in the production of oocytes and sperm cells. The proteins produced from these genes are involved in the normal process of exchanging genetic material between chromosomes in preparation for cell division during oocyte and sperm cell production. These proteins are needed to make breaks in the chromosomes so that genetic information can be exchanged.

Mutations in these genes prevent the normal function of the proteins involved in the exchange of genetic material. Without the exchange of genetic material, cell division is often stopped. In affected women, this can lead to the production of abnormal oocytes that do not contain chromosomes. When a normal sperm cell fertilizes one of these oocytes, the resulting embryo has only one set of chromosomes. Because the embryo has no genes from the mother, the pregnancy cannot develop normally, resulting in a hydatidiform mole. In women with these rare gene mutations, every pregnancy that occurs with her egg cells will result in a hydatidiform mole or pregnancy loss (miscarriage).

In some cases of recurrent hydatidiform mole, no mutations in any of the genes associated with the condition have been identified. In these instances, the cause of the condition is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Recurrent hydatidiform mole is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Recurrent hydatidiform mole seems to have an autosomal recessive inheritance pattern even when the genetic cause of the condition is unknown.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Hydatidiform moles occur in 1 in 600 to 1,000 pregnancies in western countries. One to six percent of previously affected women will have a recurrent hydatidiform mole. Gestational choriocarcinoma occurs in 1 in 20,000 to 50,000 pregnancies in the United States.

Which doctor should you see?

The suggested department for discussing Recurrent hydatidiform mole is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Recurrent hydatidiform mole. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.