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 in
infancy
Rethore 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 of
the third to sixth vertebrae of the neck
Schuffenhauer et al. (1992)
Duplications
11 Duplication 1(q12-q25) de novo PRS, hydrocephalus, PDA, pulmonary hypoplasia,
cryptorchidism, equinovarus
Chen et al. (1994)
12 Duplication 1(q23.1-q31.1) de novo PRS, brachycephaly, flexion of fingers in both hands
and camptodactyly
Aboura et al. (2002)
Translocations
9b 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 had
had several spontaneous abortions
De Lonlay-Debeney et al. (1998)
13 Unbalanced translocation der(4)t(4;11)
(q35;q23.1) mat.
PRS, dislocated hips, ASD, agenesis of corpus callosum
and of one kidney, death in infancy
Francke et al. (1977)
14 Unbalanced translocation der(10),t(3;10)
(q23;q26.3) de novo
PRS, hypertelorism, cryptorchidism, clinodactyly,
hammer toes, death in infancy
Kleczkowska et al. (1988)
15 Unbalanced translocation der(5),t(5;11)
(p15;q23) pat.
PRS, PMR, ASD and VSD, rockerbottom feet. The
father 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 XX
male (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 a
five-generation family (seven affected); PrS cosegregates
with the translocation
Stalker et al. (2001)
18 Balanced translocation t(2;17)
(q24.1;q24.3)
PRS in a three-generation family (six affected); PRS
cosegregates with the translocation
Jamshidi et al. (2004)
Mutations
19 Mutations in COL2A1(12q13.11-13.2),
COL11A2 (6p21.3), and COL11A1
(1p21)
Mutation screening of collagene types in 23 patients
with PRS. Mutations were found in seven patients.
Melkoniemi et al. (2003)
Isochromosomes
20 46, XY,i(18q) PRS, pulmonary hypoplasia, cryptorchidism, flexion
deformities of fingers
Wiswell 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 5
psychomotor 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 generally

less 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 phenotype
in campomelic dysplasia. Mansour et al. (2002) studied five
patients with campomelic dysplasia and found cleft palate in
two patients, micrognathia in five patients, and respiratory difficulties
in four patients.
SOX9 has been shown to regulate collagen expression during
cartilage and endochondral bone formation (Bell et al.,
1997; Mori-Akiyama et al., 2003). Mutations in genes coding
for collagen types have been found in patients with PRS (Table
1 and Melkoniemi et al., 2003), indicating a regulatory pathway
involving SOX9 and genes coding for collagen, whose
disruption can cause PRS. Furthermore, in a newly published
paper, Velagaleti et al. (2005) suggest that PRS may result
from dysregulation of SOX9.
CONCLUSION
Pierre Robin Sequence is a clinical well-characterized subgroup
of CL/