Filippi syndrome, also known as Syndactyly Type I with Microcephaly and Mental Retardation, is a very rare autosomal recessive genetic disease. Only a very limited number of cases have been reported to date. Filippi Syndrome is associated with diverse symptoms of varying severity across affected individuals, for example malformation of digits, craniofacial abnormalities, intellectual disability, and growth retardation. The diagnosis of Filippi Syndrome can be done through clinical observation, radiography, and genetic testing. Filippi Syndrome cannot be cured directly as of 2022, hence the main focus of treatments is on tackling the symptoms observed on affected individuals. It was first reported in 1985.
Signs and symptoms
The symptoms of Filippi Syndrome can be congenital (apparent as an infant). The occurrence and severity of such symptoms are variable across affected individuals. The progression of symptoms over one's lifetime has not been thoroughly studied due to the small number of people with Filippi Syndrome globally.
Malformations of digits
Malformations of digits are expressed among people with Filippi Syndrome. One of the most common malformations is the webbing or fusion of digits, which is termed syndactyly. In particular, syndactyly of the third and fourth fingers or the second, third and fourth toes is termed "syndactyly type 1". The degree of syndactyly may differ across affected individuals, with some exhibiting syndactyly of soft tissues and skin only, and more severe cases exhibiting syndactyly of digital bones.
Other malformations of digits include clinodactyly (curving) of the fifth fingers and brachydactyly (abnormal shortening) of digits. Brachydactyly is believed to be largely due to abnormalities arising from the bones inside the hands and feet, specifically the metacarpals and metatarsals.
Craniofacial abnormalities
Furthermore, most people with Filippi Syndrome exhibit craniofacial abnormalities. Craniofacial abnormalities are birth defects observed at the head or face region of affected individuals. Some of the craniofacial abnormalities present in people with Filippi Syndrome include microcephaly (having a skull that is smaller than normal), prominent/ elevated nasal bridge, hypertelorism (having one's pair of eyes further apart from each other than normal), and underdeveloped nasal alae (underdeveloped tissues surrounding the nostril). Less common craniofacial abnormalities include having a broad forehead, thin vermilion border (having a thin upper lip), and frontal hirsutism (having a hairy forehead).
Intellectual disability
People with Filippi Syndrome may also demonstrate varying degrees of intellectual disability. Affected individuals may experience defective speech development, aphasia (experiencing difficulty in finding the appropriate words to use), vision impairment, and an inability to speak.
Growth retardation
Another characteristic symptom of people with Filippi Syndrome is the occurrence of growth retardation, which is also referred to as growth delay. Such growth delays may be either prenatal or postnatal, meaning that they can occur both before and after birth. In particular, delayed bone maturation can be observed in patients with Filippi Syndrome.
Other symptoms
People with Filippi Syndrome may exhibit some other physical abnormalities. Examples of such abnormalities include dwarfism (having a severely short stature), dislocated elbows, decreased joint mobility, muscular hypotonia (having weak muscle tone), and involuntary muscle stiffness.
They may also exhibit abnormal conditions at their skin and teeth. Moreover, a portion of affected males may demonstrate cryptorchidism (a condition in which the testes fail to descend into the scrotum).
Causes
Filippi syndrome is a genetic disease with an autosomal recessive inheritance pattern at the Cytoskeleton Associated Protein 2 Like (CKAP2L) gene.
Inheritance pattern
An autosomal recessive inheritance pattern means that the disease trait is exhibited on an individual only when both copies of the disease gene in the individual demonstrate a specific pathogenic mutation. This happens when the individual inherits one copy of the mutated gene from each of their parents. In the case of Filippi Syndrome, both copies of the CKAP2L gene of an individual have to be mutated in order for them to demonstrate symptoms of the disorder.