Lesser forms of cleft lip associated with the branchio-oculo-facial syndrome.
Lesser forms of incomplete cleft lip (CL) have been called microform, occult, forme fruste, and congenitally healed. The association of a minimal bilateral CL in branchio-oculo-facial syndrome (BOFS) is well described and commonly referred to as a "pseudocleft." We conducted a systematic analysis of CL types in BOFS, including a retrospective cross-sectional chart and photographic review with variable longitudinal follow-up of our patients and those described in the literature. We compared data on the type of CL and palate (CL/P) and craniofacial and extracranial anomalies in patients with BOFS and classified the lesser forms CL as either minor-form, microform, or mini-microform as defined by the extent of disruption at the vermilion-cutaneous junction. The study comprised 62 patients with BOFS (1 new and 61 in literature, 4 treated by J.B.M). Forty-four patients (71%) had CL only; 16 (26%) had CL/P; and 2 patients had neither CL nor isolated CP. Thirty-five patients with CL had adequate information for analysis (defined as either seen by J.B.M., having a published photograph, or having a detailed description). The most common type was bilateral symmetrical, lesser form CL (n = 20): minor-form (n = 2), microform (n = 6), or mini-microform (n = 12). Among 17 asymmetrical forms, the left side was more severely affected side than the right (12 vs 5). Of 9 patients with CL/P and adequate clinical description, 4 were bilaterally symmetrically complete. Other anomalies, in addition to the familiar cardinal features of BOFS, included facial nerve weakness (n = 6), chin dimple or cleft of the lower lip (n = 4), upper labial pits (n = 6), minor digital anomalies (n = 12), renal anomalies (n = 14), and ectopic thymus (n = 18). This analysis reaffirms the high frequency of CL or CL/P in BOFS and the rarity of isolated cleft palate and underscores that the term "pseudocleft" lip is incorrect. The more precise lesser form designations used in this study may prove useful for future clinical studies because the causative gene, TFAP2A, is known. Lesser forms of CL may be the most subtle expression of BOFS and assist in identifying patients. Unlike major forms of CL/P, either, syndromic or non syndromic, lesser forms suggest that the developmental insult occurs later in labial formation when fusion of the medial nasal process and maxillary process is nearly complete. The deficient vermilion-mucosa and hypoplastic orbicularis oris may be the result of incomplete or deficient mesodermal penetration of the ectodermal envelope. Another possible pathogenic explanation is that failure of labial closure occurs earlier than in a major cleft when the primitive cells of ectoderm and mesoderm retain the capacity to "heal" the defect.
Genetics Unit, MassGeneral Hospital for Children, USA. lin.angela@mgh.harvard.edu
Angela E
AE
Lin
Shunsuke
S
Yuzuriha
Scott
S
McLean
John B
JB
Mulliken
D019280:Branchio-Oto-Renal Syndrome / Q000150:complications*; D002971:Cleft Lip / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D015995:Prevalence; D012189:Retrospective Studies; D050656:Transcription Factor AP-2 / Q000235:genetics; D014481:United States / Q000453:epidemiology
C493673:TFAP2A protein, human; D050656:Transcription Factor AP-2