American Journal of Medical Genetics 49:94-97 (1994) Short Rib-Polydactyly Syndrome and Pericentric Inversion of Chromosome 4 Miguel Urioste, Maria Luisa Martinez-Frias, Eva Bermejo, Nicolas Jimenez, Dolores Romero, Carmen Nieto, and Amelia Villa zyxwvuts ECEMC and Hospital Universitario Sun Carlos (M. UJ, ECEMC and Departamento de Farmacologia (M.L.M.-F.), ECEMC (E.B., A.V.), Facultad de Medicina, Universidad Complutense, Madrid; Servicio de Ginecologia, Hospital General (N.J.), and Servicio de Pediatria, Hospital General (D.R., C.N.), Segovia, Spain We report on a newborn infant with clinical and radiological manifestations of some type of short rib-polydactyly syndrome who died soon after birth. Chromosomal studies on pe- ripheral blood lymphocytes and chondro- cytes demonstrated an apparently balanced pericentric inversion of chromosome 4 (pres- ent in the mother also). This association may have occurred by chance but, if not, the chro- mosomal breakpoints could interrupt the gene responsible for short rib-polydactyly syndromes, or else be related to the mecha- nism of short rib-polydactylysyndromes. zyxwv 0 1994 Wiley-Liss, Inc. KEY WORDS: short rib-polydactyly syn- dromes, pericentric inver- sion of chromosome 4, tenta- tive chromosomal gene loca- tion, chondrocyte culture, chondrodysplasia, chromo- somal abnormality INTRODUCTION zyxwvut Chromosomal studies carried out in patients with Mendelian disorders or distinctive multiple congenital anomalies syndromes have been applied to the search for visible chromosomal rearrangements that would give some clue to the location of the disease gene. In some instances the molecular search for the gene assign- ment can be initiated by a report in which a cytogenetic rearrangement and a well-known phenotype are asso- ciated. This happens in disorders with recognized Mendelian inheritance, as in many autosomal domi- nant conditions, such as Greig cephalopolysyndactyly syndrome [Tommerupand Nielsen, 19831, or autosomal Received for publication April 5,1993; revision received August 9, 1993. Address reprint requests to Dr. Miguel Urioste, ECEMC, Facul- tad de Medicina, Universidad Complutense, 28040 Madrid, Spain. 0 1994 Wiley-Liss, Inc. recessive conditions, such as Zellweger syndrome [Naritomi et al., 19891,as well as in heterogeneous enti- ties, such as the Mobius anomaly [Ziter et al., 19771. We report on a patient with short rib-polydactyly syn- drome (SRPS), an autosomal recessive condition, who also had an associated familial chromosomal rearrange- ment. This unusual association suggests a tentative chromosomal location for the gene or mechanism that is responsible for SRPS. This child was identified through the Spanish Collaborative Study of Congenital Malfor- mations [see Martinez-Frias et al., 1991 for ECEMC methodology]. CLINICAL REPORT The propositus was a male born to a 34-year-old mother and a 33-year-old father. The parents were healthy and nonconsanguineous. The mother had had z 4 earlier pregnancies which resulted in a normal male and 3 spontaneous abortions of unknown cause. This pregnancy was complicated by vaginal bleeding and polyhydramnios, and the mother had morning sickness during the first trimester. Fetal movements started at the 5th month of pregnancy. There was no history of prenatal exposure to drugs. The presence of short femora and humeri was docu- mented by ultrasound in the second trimester. Delivery was induced at 29 weeks gestation and the baby died 1 hr after birth. Birthweight was 1,500 g (50th centile), length 37 cm (25th centile), crown-rump length 28 cm (90th centile), and OFC 28 cm (50th centile). On physical examination, the infant had a “saddle” nose, a medial cleft in the upper lip which was fused to the gum, and whitened hamartomatous lesions on the tongue and gums (Fig. 1). He also had a narrow chest (Fig. 2), a bilateral simian crease, short limbs, talipes equinovarus, preaxial and postaxial polysyndactyly of hands (2 extra fingers) with a gap between his third and fourth fingers, and preaxial polysyndactyly only of feet (1 extra digit).External genitalia were male; micropenis and bilateral cryptorchidism were evident. The radiological findings were complete situs inver- sus and the salient skeletal abnormalities including short and horizontal ribs, a pelvis with trident-shaped lower margins and lateral iliac notches, and short tubu-