Overview

What is Filippi's syndrome? Filippi's syndrome is an ultra-rare genetic disorder with birth evidence, characterized by an atypical appearance, anomalies of fingers, and mental retardation ranging from mild to profound. Primary physical findings may include growth delays; some fingers and toes may be fused (syndactyly) and microcephaly. Microcephaly is a neurological disorder where the circumference of the head is smaller than what would be expected according to an individual's age and sex. The transmission of Filippi syndrome is by an autosomal recessive pattern.¹

Risk factors

• A child born to families positive with a history of the Filippi Syndrome genetic condition have a higher risk of getting Filippi Syndrome. People who have consanguineous partners/spouses have the highest risk
• It is important to note that having a risk factor does not mean you will get the condition. It merely indicates a higher likelihood of developing a certain condition than the one having no risk factors at all. Some are more important than others
• Moreover, the lack of a risk factor does not mean that an individual will not develop the condition. Always speak with your healthcare provider about the influence of risk factors²

Causes

Filippi syndrome is transmitted as an autosomal recessive trait; it is caused specifically by mutations in the CFAP298 gene. This means that genetic diseases are determined by two genes: One from the father and one from the mother.³

Recessive genetic disorders occur when an individual receives two abnormal genes for the same trait, one from each parent. For example, if the gene of the disease was obtained from one parent and another is a normal gene, then such a person is termed to be a carrier of the disease, although most likely not having symptoms.

It concludes that there is a 25% chance with every pregnancy that the child will receive the defective gene from both carrier parents, and itt means that one in every four fertilized eggs is likely to be affected.

There is also an opportunity for each pregnancy to have a child who is a carrier like the parents, in 50% of cases. The probability for a child to receive normal genes from his or her parents and be normal genetically on a certain trait is equal to 25%. Some cases of Filippi syndrome have occurred in individuals whose parents are related, such as cousins. All people carry 1-2 abnormal genes. Parents who are first cousins have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk of having children with a recessive genetic disorder.¹

Sign and Symptoms

Individuals with Filippi syndrome exhibit a variety of distinctive features,¹ including:

• In facial dysmorphism, characteristic facial features seen are high forehead, broad nasal bridge, thin nostrils, thin upper lip, and hypertelorism
• Microcephaly means very small head size, relating most often to developmental delays
• Syndactyly: Is the joining of fingers and/or toes, usually involving soft tissue of quantitatively involved digits. It is also called type 1 syndactyly when it involves partial or complete webbing of these quantitatively affected digits. The extent of syndactyly may range from excessive webbing or skin to the fusion of bone within the involved digits
• Additional digital abnormalities may characterize Filippi syndrome. In some cases, there may be an inward deviation known as the clinodactyly of the fifth fingers or pinkies. The fingers and toes can also look unusually short: brachydactyly, most often due to the abnormalities of bones within those body parts—the metacarpals and metatarsals of the hands and feet
• Intellectual Disability: Its severity ranges from mild to severe, but most of the affected individuals often exhibit gross developmental delays
• Growth Retardation: It may leave a person with small stature and disturbed physical development
• Additional Anomalies: Other possible features include cleft palate, cryptorchidism, and various skin and dental abnormalities

Diagnosis

Diagnostic tests for Filippi Syndrome can be carried out on pregnant women or on the newborn child². These include:

• Ultrasonography done on pregnant women permits observation of the characteristic signs of Filippi Syndrome
• Examination of the newborn child and case history of family
• Common features of Filippi Syndrome that basically help in assessing the condition are:
  • Small head size
  • Fused digits/webbing on the limbs
  • Distinctive facial appearance
  • Growth delays

Many clinical conditions could present with similar sets of signs and symptoms. More tests may be conducted by your health-care provider to make sure that other clinical conditions are excluded before arriving at a clear diagnosis.

Differential diagnosis

• KBG syndrome
• Scott craniodigital syndrome
• Blepharonasofacial syndrome 

Complications

Complications due to Filippi Syndrome may include:

• Severe mental retardation, learning disabilities
• Cleft palate
• Short stature

Treatment

Care is directed to the specific symptoms presented and the needs of an affected individual; treatment requires the interaction and collaboration of a multidisciplinary team of professionals. Individuals with Filippi syndrome may be provisioned with a systematic and comprehensive treatment plan to include medical and healthcare professionals, which may involve paediatricians, orthopaedists, physicians congenitally specializing in the skeleton, joints, muscles and the myriad of soft and supportive tissue-related structures. Other healthcare professional involvement is also included.¹

In some cases of its occurrence, treatment may involve surgical correction of related skeletal or other abnormalities that could be associated with the disorder. Surgical procedures will be performed depending upon the severity of the anatomical abnormalities, their associated symptoms, and other factors. 

Early intervention may be important to ensure that affected children reach their potential. Special services that might benefit these children include special education, physical therapy, speech therapy, or other medical, social, and/or vocational 

Prognosis

• With timely and active treatment administration, Filippi Syndrome can be effectively managed and controlled²
• Nevertheless, most children suffer from moderate (and sometimes acute) developmental delays with mental retardation

FAQs

Who gets Filippi Syndrome?

Filippi syndrome is a very rare, congenital condition.

How is Filippi syndrome diagnosed?

Filippi syndrome is typically diagnosed through clinical evaluation, genetic testing to identify mutations in the gene, and imaging studies to assess brain abnormalities.

Is there a cure for Filippi syndrome?

There is currently no cure for Filippi syndrome. Treatment is mainly the control of symptoms with medicines to manage seizures, speech therapy, physical therapy, and management behaviorally.

What is the prognosis for individuals with Filippi syndrome?

The prognosis for individuals with Filippi syndrome can vary depending on the severity of symptoms. Some individuals may have moderate intellectual disability and lead relatively independent lives, while others may have more severe intellectual disability and require full-time care.

How can Filippi Syndrome be Prevented?

Up until now, there has been no certain ways or tips to prevent Filippi Syndrome genetic condition. While genetic testing of the expecting parents and prenatal diagnosis by molecular testing of the foetus during pregnancy may be done, the exact risks will become clearer during pregnancy. If it runs in a family, then genetic counseling will help assess risks, before planning for a child. Active research is currently being performed to explore the possibilities of treatment and prevention of inherited and acquired genetic disorders.

Is Filippi syndrome inherited?

Filippi syndrome is inherited in an autosomal recessive manner, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to develop the disorder. Parents of an affected individual are typically carriers of the gene mutation.

Summary

Filippi syndrome represents a very rare genetic disorder characterized by typical dysmorphic features, anomalies in the fingers and toes, retarded growth, mild to severe mental retardation, and an autosomal recessive pattern of transmission. As this is an autosomal recessive transmission, both parents have to pass on the abnormal gene for a child to develop this syndrome. The risk factors for this syndrome are a positive family history of the condition and consanguinity. Diagnosis can usually be made by physical examination, family history review, and genetic testing. Treatment is generally directed toward management of symptoms and thus surgery for skeletal abnormalities and early intervention services. Prognosis varies with the severity of symptoms; some patients lead relatively independent lives, while others require full-time care. The cure for Filippi syndrome is still unknown, but its prevention methods include genetic testing, prenatal diagnosis, and genetic counseling.