Introduction 

Filippi syndrome is a rare genetic disorder that affects less than one in a million people. There have been only 25-30 reported cases of this syndrome worldwide. Individuals affected by this condition may have characteristic facial features (bulging forehead with broad nasal bridge) with webbed or conjoined fingers or toes, smaller head (microcephaly), delayed growth, and learning disabilities.^1,2,3

What causes filippi syndrome?

Filippi syndrome occurs due to a change or mutation in the CKAP2L gene. This gene is responsible for maintaining the cell structure and cell division. Filippi syndrome is inherited in an autosomal recessive manner, which means two copies of the faulty gene should be present in a child for this disorder to occur. In most cases, both parents of an affected child have one faulty gene (parents are called carriers of the mutation) which they pass on to their child. Sometimes, only one parent has a faulty gene and the other parent has a normal gene. When these two genes are passed on to the child, the normal gene changes or mutates into a faulty gene randomly and the child develops this syndrome, although the chances of this later scenario to happen are extremely rare, but not impossible.⁴ 

Genetic testing for filippi syndrome

What is genetic testing and how can it help the families? 

Genetic testing is the analysis of a person’s DNA to diagnose rare genetic disorders. It can help to identify the presence or the risks of having certain conditions in you, your children or other family members. 

Types of genetic tests 

Targeted gene testing

If the external features of an individual indicate Filippi syndrome, then clinicians can advise targeted gene sequencing of the CKAP2L gene to find the mutations and confirm the diagnosis.

Whole exome sequencing (WES)

As this is a rare genetic condition, WES is highly useful when the presence of this syndrome is not initially suspected the clinical picture is unclear, and other routine tests failed to diagnose the condition. The entire coding region of the genome is sequenced by WES to identify rare genetic conditions.³

Carrier testing

Carrier testing is done for the family members to identify if any of the parents is a carrier of the mutation. This helps them to make informed decisions about future pregnancies.

Prenatal genetic testing

If any member of the family is already affected by Filippi syndrome, prenatal genetic testing is conducted during pregnancy to determine if the foetus has the disorder or not. Prenatal testing is done by taking the sample (foetal cells) from the amniotic fluid or chorionic villi tissue from the pregnant mother and then the genetic testing is done to identify if the baby is affected or not. Nowadays, a non-invasive method is also available – foetal DNA (also called as cell-free foetal DNA) can be obtained/extracted from a pregnant mother’s blood, and then genetic testing is performed. Although the amount of foetal DNA obtained by this method is less in quantity, and can be contaminated by the mother’s DNA – that needs to be removed before proceeding with genetic testing.² 

Genetic counselling for filippi syndrome 

Counselling before testing 

Review of family history

Genetic counsellors take the detailed family history of the couple and based on this, they discuss what the family can expect from the results. 

Discussing the available genetic tests

Based on family history, genetic counsellors discuss the available tests what they can, and can't reveal to the family, and the possible implications of the results. 

Counselling after testing

Discussing the test results

The genetic counsellors, along with the team of specialist doctors, reveal and help the family to understand the results. They explain to the family members the importance of favourable, negative, or inconclusive outcomes.

Providing emotional support and counselling to the family

Positive results or a diagnosis of a rare genetic disorder like Filippi can be devastating for the family. Genetic counsellors provide emotional support to the family and offer guidance towards the right resources to obtain further help related to management and treatment options available.² 

Future family planning options: 

If any of the parents is a carrier or there has been a family history of this syndrome, the counsellor discusses the options related to adoption, prenatal testing or IVF (in-vitro fertilisation) with preimplantation genetic testing/diagnosis.

Management and care planning

Coordinating care

Filippi syndrome usually affects multiple organs and body parts. Counsellors help the family to coordinate with a team of specialists such as a paediatrician, neurologist, speech therapist etc., so that the patients can receive a comprehensive care plan for the management of the condition.   

Referring useful resources to the family

There is no treatment for this condition but with proper resources and support groups, affected families can learn from each other's experiences and know what to expect. Additionally, by being connected to organisations that specialise in the management of rare genetic conditions, families can support and care for their affected family members in the best possible ways.³

Importance of genetic counselling 

Helping parents understand the inheritance patterns

Filippi syndrome is inherited in an autosomal recessive manner, which means both parents pass on one copy of the faulty gene. 

Genetic counselling assists families in making informed decisions that benefit both parents and impacted members, as well as in seeking better resources to make their lives more comfortable.⁴

Summary

Genetic disorders are rare conditions, and their diagnosis depends on multiple variables, such as the availability of medical facilities and related resources, financial opportunities, and the disease-awareness of the family. In some cases, the diagnosis isn’t defined until the late stage of childhood. Furthermore, being diagnosed with a rare genetic illness can be traumatic for a family. Given the complexity and absence of a treatment for most of the genetic disorders, parents may become overwhelmed, delaying their pursuit of adequate medical care. Therefore, genetic counselling has become an essential component of management and care plans for genetic disorders. Working with a specialised genetic counsellor can help parents understand the course of genetic disorders, what to expect, how to manage symptoms, where to get the right services, and how to do their family planning.  

FAQs

What are the symptoms of the filippi syndrome? 

The symptoms of Filippii syndrome can vary from mild to severe, depending on the patient. The most common symptoms are microcephaly, webbed toes or fingers, distinct facial features like a broad nasal bridge and bulging head, learning difficulties, and short height. 

What is filippi syndrome? 

It is a rare genetic disorder that occurs due to a mutation in a gene called CKAP2L. It is an extremely rare disorder and only 25-30 people are known to have this condition worldwide. 

What does filippi syndrome look like?

A person affected by Fillipi syndrome will have unique facial features, webbed toes or fingers, a small head, short height, broad forehead, delayed growth and they often have learning difficulties.