# Popliteal pterygium syndrome

Popliteal pterygium syndrome (PPS) is an inherited condition affecting the face, limbs, and genitalia. The syndrome goes by a number of names including the popliteal web syndrome and, more inclusively, the facio-genito-popliteal syndrome. The term PPS was coined by Gorlin et al. in 1968 on the basis of the most unusual anomaly, the popliteal pterygium (a web behind the knee).

## Symptoms and signs

Clinical expressions of PPS are highly variable and display different combinations of abnormalities depending on the individual, but include the following:
* Limb findings: popliteal webbing which is webbing of fusion of the skin behind the knee which restricts leg extension, malformed toenails, fusion of finger or toes known as syndactyly, talipes (foot is twisted out of normal position), and missing or underdeveloped fingers or toes.
* Facial findings: cleft palate with or without cleft lip, pits in the lower lip, fibrous bands in the mouth known as syngnathia, and a partial or complete fusion of eyelids at birth (ankyloblepharon).
* Genital findings: hypoplasia of the labia majora, malformation of the scrotum, and cryptorchidism.

## Genetics

The genetic locus for PPS was localized to chromosome 1 in 1999. The disorder is inherited in an autosomal dominant manner and is due to mutation of the IRF6 gene. Most reported cases are sporadic; advanced parental age is found in a number of these cases, suggesting new mutations.
The term PPS has also been used for two rare autosomal recessively inherited conditions: Lethal PPS and PPS with Ectodermal Dysplasia. Although both conditions feature a cleft lip/palate, syngnathia, and popliteal pterygium, they are clinically distinguishable from the autosomal dominant case. Lethal PPS is differentiated by microcephaly, corneal aplasia, ectropion, bony fusions, hypoplastic nose and absent thumbs, while PPS with Ectodermal Dysplasia is differentiated by woolly hair, brittle nails, ectodermal anomalies, and fissure of the sacral vertebrae.

### Relationship to Van der Woude syndrome

Van der Woude syndrome (VDWS) and popliteal pterygium syndrome (PPS) are allelic variants of the same condition; that is, they are caused by different mutations of the same gene. PPS includes all the features of VDWS, plus popliteal pterygium, syngnathia, distinct toe/nail abnormality, syndactyly, and genito-urinary malformations.

### Relationship to Bartsocas-Papas syndrome

Bartsocas-Papas syndrome is a form of popliteal pterygium syndrome and is a very rare disease characterized by congenital craniofacial anomalies, popliteal webbing, and genitourinary and musculoskeletal anomalies. It was first described by Dr. Christos Bartsocas and is more specifically an autosomal recessive popliteal pterygium syndrome.

## Diagnosis

Popliteal Pterygium Syndrome (PPS) can be diagnosed prenatally through ultrasound and confirmed via genetic testing. Ultrasound imaging can identify characteristic physical anomalies associated with PPS, including popliteal webbing, lower limb abnormalities (such as bilateral equinovarus feet, syndactyly, and ectrodactyly), facial abnormalities (such as cleft lip), and ambiguous genitalia. While these markers are not exclusive to PPS, the presence of multiple anomalies suggests the possibility of the condition.
Definitive diagnosis can be achieved through genetic testing, which detects mutations in the IRF6 gene, known to be associated with PPS. Fetal DNA, obtained from cord blood, amniocentesis, or chorionic villus sampling, can undergo whole-exome sequencing to confirm the presence of an IRF6 gene mutation. In cases where a de novo mutation is detected, the risk of recurrence in future pregnancies is significantly lower than in familial cases.

## Treatment

Popliteal Pterygium Syndrome (PPS) does not typically affect cognitive development, and individuals with the condition generally exhibit normal mental development. Treatment is primarily surgical and focuses on correcting limb, facial, and genital abnormalities associated with the syndrome. Depending on the severity of the anomalies, multiple reconstructive surgeries may be required to improve mobility, appearance, and function. While the prognosis is generally favorable, the extent of physical disabilities and the need for surgical intervention vary among affected individuals.

## Epidemiology

The diagnosis of PPS has been made in several ethnic groups, including Caucasian, Japanese, and sub-Saharan African. Males and females are equally likely to have the syndrome. Since the disorder is rare, its incidence rate is difficult to estimate, but is less than 1 in 300,000.