Treatment Outcomes in Patients with Van der Woude and Popliteal Pterygium Syndromes Compared to Patients with Nonsyndromic Cleft Lip/Palate

Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are allelic autosomal dominant disorders caused by mutations in interferon regulatory factor 6 (IRF6).  They comprise the single most common syndromic cause of cleft lip and/or palate (CL/P), accounting for 2% of all cases. VWS is characterized by CL/P and lower lip sinuses; PPS has the same features as VWS plus popliteal webbing, genital malformations, and syngnathia. The aim of this study is to summarize the clinical characteristics and treatment outcomes for patients with VWS/PPS and compare them to those for patients with nonsyndromic CL/P.  We hypothesize that patients with VWS/PPS have more severe clefting with higher revision rates, impaired facial growth, and worse speech outcomes compared to patients with nonsyndromic CL/P.

Retrospective chart review of all patients with VWS/PPS seen at Boston Children’s Hospital from 1979 to 2012. Age, sex, family history, cleft type, operative procedures, speech outcomes, and midfacial growth were documented. These data were compared to patients with nonsyndromic CL/P treated at the same tertiary care center.

There were 28 patients with VWS (n=21)/PPS (n=7): 18 females (64%), 10 males (36%), and 18 patients (64%) with a family history of VWS/PPS. The distribution of clefting included 8 patients (29%) with cleft palate, 16 (57%) with cleft lip and palate [5 (18%) with unilateral complete (3 left, 2 right), 8 (29%) with bilateral complete, and 3 (11%) with bilateral asymmetric (2 left complete and right microform, 1 right complete and left incomplete)], 1 (4%) with bilateral complete cleft lip and alveolus with intact secondary palate, 1 (4%) with occult submucous cleft palate, and 2 (7%) with lower lip sinuses only.

Among the 24 patients with cleft palate with or without cleft lip, Veau types I, II, III, and IV were found in 4 (17%), 4 (17%), 5 (21%), and 11 patients (46%), respectively. Among the 24 patients with Veau type I-IV cleft palate, 10 (42%) had hypoplastic hard palatal shelves and 9 (38%) had palatal fistula. Of the 23 patients age 4 or older with Veau type I-IV or occult submucous cleft palate, 10 (43%) required a pharyngeal flap to manage VPI.  Of the 22 patients age 5 or older with Veau type I-IV cleft palate, 14 (64%) had midfacial retrusion.

Clefting characteristics and treatment outcomes for patients with VWS/PPS were compared to existing data for patients with nonsyndromic CL/P. The Fisher’s exact test demonstrated a difference in the distribution of Veau types between patients with VWS/PPS and nonsyndromic CL/P (p = 0.0028), with a higher incidence of type IV clefts and a lower incidence of type III clefts in VWS/PPS (p = 0.0016) than in nonsyndromic patients. The incidence of palatal fistula (p < 0.0001), midfacial retrusion (p < 0.0001), and the need for a pharyngeal flap (p = 0.0014) were significantly higher in patients with VWS/PPS.

Patients with VWS/PPS have more severe forms of oral clefting and higher incidences of impaired speech, palatal fistula, and midfacial retrusion. These findings may help clinicians to counsel families and plan long-term interdisciplinary care for patients with these disorders.

References:

1. Kondo S et al.  Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.  Nature Genetics.  32: 285-289 (2002).

2. Rizos M and Spyropoulos MN. Van der Woude Syndrome: a review. Cardinal signs, epidemiology, associated features, differential diagnosis, expressivity, genetic counseling and treatment. European Journal of Orthodontics. 26(1): 17-24 (2004).