Popliteal pterygium syndrome

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Popliteal pterygium syndrome
Popliteal Pterygia, Lip Pits, Cleft Lip and Palate 1.jpg
Image depicts pits in the lower lip, a signature facial symptom of PPS
Specialty Medical genetics   OOjs UI icon edit-ltr-progressive.svg
CausesMutation to IRF6 gene
Diagnostic method Genetic testing and prenatal ultrasound screening
TreatmentSurgery
Frequency1 in 300, 000 births

Popliteal pterygium syndrome (PPS) is a rare inherited genetic disorder characterized by distinctive craniofacial, musculoskeletal and genitorourinary symptoms. It is primarily caused by a mutation to the IRF6 gene and follows an autosomal dominant inheritance pattern. The syndrome is associated with many features such as popliteal webbing (pterygium), cleft lip or palate, syndactyly, and genetic anomalies with the severity and expression of each symptom varying between affected individuals. PPS has an approximate incidence rate of 1 in every 300 000 live births. The condition was first described by Trélat in 1869 and later named by Gorlin and colleagues in 1968. The term pterygium is derived from the Greek word for "wing," referring to the wing-like tissue structures often observed in affected individuals.

Contents

Symptoms and signs

Clinical expressions of PPS are highly variable and display different combinations of abnormalities depending on the individual, but include the following: [1] [2] [3]

Image depicting popliteal webbing (webbing of the knee) Popliteal Pterygia, Lip Pits, Cleft Lip and Palate 5.jpg
Image depicting popliteal webbing (webbing of the knee)

Genetics

Image depicts autosomal dominant inheritance patterns Autosomal dominant - en.svg
Image depicts autosomal dominant inheritance patterns

Popliteal pterygium syndrome is caused by mutations in the IRF6 gene, which follow an autosomal dominant mode of inheritance. [4] The IRF6 gene encodes a transcription factor. Mutations of this gene associated with PPS occur in the DNA-binding domain, which prevents the IRF6 protein from interacting with its target DNA sequence; this affects the expression of target genes that result in the observed PPS symptoms. [4]

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. [5]

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 in the IRF6 gene. Mutations associated with VDWS are different from PPS, in that they occur in regions of the IRF6 protein not directly involved in DNA-binding; observed mutations have caused protein truncation, inability to form protein complexes, or inability to bind DNA. [4] PPS includes all the features of VDWS, plus popliteal pterygium, syngnathia, distinct toe/nail abnormality, syndactyly, and genito-urinary malformations. [6]

Relationship to Bartsocas-Papas syndrome

Bartsocas-Papas syndrome is a form of popliteal pterygium syndrome caused by an autosomal recessive mutation in the RIPK4 gene. [7] It is a rare disease characterized by congenital craniofacial anomalies, popliteal webbing, and genitourinary and musculoskeletal anomalies.

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. [8]

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. [8]

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. [8]

Epidemiology

Popliteal pterygium syndrome (PPS) is a rare genetic disorder with an estimated incidence of approximately 1 in 300,000 births. [9] It is inherited in an autosomal dominant pattern, as evidenced by a case in which a healthy mother and father had four out of nine pregnancies definitively affected by PPS. [10] The syndrome has been reported in diverse populations and is not associated with any specific haplogroups or ethnic groups. [11]

See also

References

  1. Parikh SN, Crawford AH, Do TT, Roy DR (May 2004). "Popliteal pterygium syndrome: implications for orthopaedic management". J Pediatr Orthop B. 13 (3): 197–201. doi:10.1097/01202412-200405000-00010. PMID   15083121.
  2. "Popliteal pterygium syndrome: MedlinePlus Genetics".
  3. Qasim, Muhammad; Shaukat, Mahmood (2012). "Popliteal pterygium syndrome: a rare entity". APSP Journal of Case Reports. 3 (1): 5. ISSN   2218-8185. PMC   3418038 . PMID   22953299.
  4. 1 2 3 Kondo, Shinji; Schutte, Brian C.; Richardson, Rebecca J.; Bjork, Bryan C.; Knight, Alexandra S.; Watanabe, Yoriko; Howard, Emma; Ferreira de Lima, Renata L. L.; Daack-Hirsch, Sandra; Sander, Achim; McDonald-McGinn, Donna M.; Zackai, Elaine H.; Lammer, Edward J.; Aylsworth, Arthur S.; Ardinger, Holly H. (2002). "Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes". Nature Genetics. 32 (2): 285–289. doi:10.1038/ng985. ISSN   1546-1718. PMC   3169431 . PMID   12219090.
  5. Cardoso, E. R. L.; Hawary, M. B.; Mahmud, S. (1998-04-01). "A recessively inherited non-lethal form of popliteal pterygium syndrome" . British Journal of Oral and Maxillofacial Surgery. 36 (2): 138–140. doi:10.1016/S0266-4356(98)90183-8. ISSN   0266-4356. PMID   9643601.
  6. Wong FK, Hagg U (October 2004). "An update on the aetiology of orofacial clefts". Hong Kong Med J. 10 (5): 331–6. PMID   15479962.
  7. Kalay, Ersan; Sezgin, Orhan; Chellappa, Vasant; Mutlu, Mehmet; Morsy, Heba; Kayserili, Hulya; Kreiger, Elmar; Cansu, Aysegul; Toraman, Bayram; Abdalla, Ebtesam Mohammed; Aslan, Yakup; Pillai, Shiv; Akarsu, Nurten A. (2012). "Mutations in RIPK4 Cause the Autosomal-Recessive Form of Popliteal Pterygium Syndrome". The American Journal of Human Genetics. 90 (1): 76–85. doi:10.1016/j.ajhg.2011.11.014. ISSN   0002-9297. PMC   3257895 . PMID   22197489.
  8. 1 2 3 Traisrisilp, Kuntharee; Luewan, Suchaya; Sirilert, Sirinart; Jatavan, Phudit; Tongsong, Theera (October 2021). "Prenatal Sonographic and Molecular Genetic Diagnosis of Popliteal Pterygium Syndrome". Diagnostics. 11 (10): 1819. doi: 10.3390/diagnostics11101819 . ISSN   2075-4418. PMC   8534560 . PMID   34679516.
  9. Bennun, Ricardo D.; Stefano, Eduardo; Moggi, Luis E. (September 2018). "Van der Woude and Popliteal Pterygium Syndromes" . Journal of Craniofacial Surgery. 29 (6): 1434–1436. doi:10.1097/SCS.0000000000004698. ISSN   1049-2275. PMID   29916977.
  10. Bartsocas, C S; Papas, C V (1972-06-01). "Popliteal pterygium syndrome. Evidence for a severe autosomal recessive form". Journal of Medical Genetics. 9 (2): 222–226. doi:10.1136/jmg.9.2.222. ISSN   1468-6244. PMC   1469049 . PMID   4339984.
  11. Giuliani, R.; Trivisonno, A. (October 2000). "[A rare case of popliteal pterygium syndrome]". Il Giornale di Chirurgia. 21 (10): 379–382. ISSN   0391-9005. PMID   11126735.