Schematic diagrams of the development of the lip and palate in humans. (A) The developing frontonasal prominence, paired maxillary processes and paired mandibular processes surround the primitive oral cavity by the fourth week of embryonic development. (B) By the fifth week, the nasal pits have formed, which leads to formation of the paired medial and lateral nasal processes. (C) The medial nasal processes have merged with the maxillary processes to form the upper lip and primary palate by the end of the sixth week. The lateral nasal processes form the nasal alae. Similarly, the mandibular processes fuse to form the lower jaw. (D) During the sixth week of embryogenesis, the secondary palate develops as bilateral outgrowths from the maxillary processes which grow vertically down the side of the tongue. (E) Subsequently, the palatal shelves elevate to a horizontal position above the tongue, contact one another and commence fusion. (F) Fusion of the palatal shelves ultimately divides the oronasal space into separate oral and nasal cavities. Figure is modified with permission from REF 68 Copyright permission**

A: A collection of images of different types of clefts, some with associated anomalies such as lip pits.¹¹¹ a–c, Van der Woude syndrome cases with associated lip pits; d, isolated cleft palate only; e, isolated unilateral cleft lip and palate; f–m, syndromic forms of clefting (f, CLP in Smith-Lemli-Opitz syndrome; g, midline cleft in holoproencephaly; h, bilateral CLP in TGIF mutation case and I, bilateral CLP in SHH variant; j, midline notch in OFD type 1; k, repaired cleft in MID1 mutation; l, repaired unilateral CLP and; m, pseudo cleft lip). [Legend to be modified depending on images provided. Include image permission details.]
B: A set of illustrative drawings of CLP types.¹¹¹ a and e show unilateral and bilateral clefts of the soft palate; b, c and d show degrees of unilateral cleft lip and palate; f, g and h show degrees of bilateral cleft lip and palate. This figure is modified from REF. 111, with permission. Copyright Macmillan 2002.

a: Photographs of the upper lip region for each member of a nuclear family with two family members affected with nonsyndromic CLP (surgically repaired). The other three family members do not have externally visible defects, but two of them have sub-clinical defects of the orbicularis oris muscle (pedigree symbols circled in red).
b: The upper lip ultrasounds of each member of the family shown in panel a. Note the disruptions in the orbicularis oris muscle in the two people with CLP in the family, plus in two people with no external manifestation (pedigree symbols circled in red).