Deletion 4q31-qter de novo PRS, PMR, depressed nasal bridge, clinodactyly Davis et al. (1981)5 Deletion 4q32-4qter (unknown origin) PRS and PMR Fryns et al. (1981)6 Deletion 4q33-qter de novo PRS, short left forearm, hip dysplasia Menko et al. (1992)7 Deletion 4q32.1-qter de novo PRS, cardiac and pulmonary malformations, death ininfancyRethore et al. (1979)8 Deletion 4q33 de novo PRS, clinodactyly, PFO Strehle et al. (2001)9a Deletion 11q21-q23 de novo PRS, PMR, renal and cardiac malformations De Lonlay-Debeney et al. (1998)10 Deletion 16q12.1-q13 de novo PRS, PMR, hypertelorism, dysplastic hips, fusion ofthe third to sixth vertebrae of the neckSchuffenhauer et al. (1992)Duplications11 Duplication 1(q12-q25) de novo PRS, hydrocephalus, PDA, pulmonary hypoplasia,cryptorchidism, equinovarusChen et al. (1994)12 Duplication 1(q23.1-q31.1) de novo PRS, brachycephaly, flexion of fingers in both handsand camptodactylyAboura et al. (2002)Translocations9b Unbalanced translocation der(22)t(11;22)(q23;q11.2) mat.PRS, renal and cardiac malformations, perinatal death.The mother had a balanced translocation and hadhad several spontaneous abortionsDe Lonlay-Debeney et al. (1998)13 Unbalanced translocation der(4)t(4;11)(q35;q23.1) mat.PRS, dislocated hips, ASD, agenesis of corpus callosumand of one kidney, death in infancyFrancke et al. (1977)14 Unbalanced translocation der(10),t(3;10)(q23;q26.3) de novoPRS, hypertelorism, cryptorchidism, clinodactyly,hammer toes, death in infancyKleczkowska et al. (1988)15 Unbalanced translocation der(5),t(5;11)(p15;q23) pat.PRS, PMR, ASD and VSD, rockerbottom feet. Thefather had a balanced translocation and was unaffected.Wallerstein et al. (1992)16 Balanced translocation t(16;17)(p13;q21)pat.The father had a translocation and was unaffected.The proband had a normal karyotype but was XXmale (sex reversal) and had PRS, PMR, and scoliosis.Petrus et al. (1981)17 Balanced translocation t(13;17)(q22.1;q23.3)PRS, skeletal defects and multiple miscarriages in afive-generation family (seven affected); PrS cosegregateswith the translocationStalker et al. (2001)18 Balanced translocation t(2;17)(q24.1;q24.3)PRS in a three-generation family (six affected); PRScosegregates with the translocationJamshidi et al. (2004)Mutations19 Mutations in COL2A1(12q13.11-13.2),COL11A2 (6p21.3), and COL11A1(1p21)Mutation screening of collagene types in 23 patientswith PRS. Mutations were found in seven patients.Melkoniemi et al. (2003)Isochromosomes20 46, XY,i(18q) PRS, pulmonary hypoplasia, cryptorchidism, flexiondeformities of fingersWiswell and Edwards (1986)* Only articles with genetic and clinical information were included. Case 9 is listed twice because the authors report two cases (one with a deletion and one with a translocation). PMR 5psychomotor retardation; PFO 5 patent foramen ovale; PDA 5 patent ductus arteriosus; ASD 5 atrial septal defects; VSD 5 ventricular septal defects. Explanation of the unbalanced translocations:der(n) is the chromosome missing material; the other chromosome has partial trisomy.

Patients with breakpoints outside the coding region are generallyless severely affected than are patients with mutations

in the SOX9 coding region (Wagner et al., 1994; Pfeifer et al.,1999). Pierre Robin Sequence is often part of the phenotypein campomelic dysplasia. Mansour et al. (2002) studied fivepatients with campomelic dysplasia and found cleft palate intwo patients, micrognathia in five patients, and respiratory difficultiesin four patients.SOX9 has been shown to regulate collagen expression duringcartilage and endochondral bone formation (Bell et al.,1997; Mori-Akiyama et al., 2003). Mutations in genes codingfor collagen types have been found in patients with PRS (Table1 and Melkoniemi et al., 2003), indicating a regulatory pathwayinvolving SOX9 and genes coding for collagen, whosedisruption can cause PRS. Furthermore, in a newly publishedpaper, Velagaleti et al. (2005) suggest that PRS may resultfrom dysregulation of SOX9.CONCLUSIONPierre Robin Sequence is a clinical well-characterized subgroupof CL/