Prenatal diagnosis of trisomy 21 and semilobar holoprosencephaly. Presentation of a rare association

We present the first case reported in the Republic of Colombia of associated trisomy 21-holoprosencephaly, one of the few in the world literature. The patient was a male newborn, the son of a healthy primiparous 19 year old. An obstetric sonogram at 27 weeks gestation revealed the foetus with both cerebral ventricles dilated, semilobar holoprosencephaly and cleft lip and palate. The mother received a detailed ultrasound scan and amniocentesis for foetal cytogenetic study. A caesarean section was performed at 38 weeks. The newborn weighed 2200 g and was 46 cm long. The head circumference was 28 cm; thoracic girth, 28.5 cm; and abdominal girth, 27 cm. Apgar score was 6 at 1 min, 6 at 5 min and 9 at 10 min. Physically, the newborn had a full moon face, mongoloid obliquity of the palpebral fissure, nasal bone hypoplasia, micrognathia and cleft lip and palate. Simple and contrast computed axial tomography of the brain showed semilobar holoprosencephaly and cleft lip. At 25 h of life, the newborn expired from respiratory arrest.

Prenatal chromosome analysis presented a 47, XY, +21 G-band karyotype. Postnatal cytogenetic analysis, performed on umbilical cord blood using the fluorescent in situ hybridisation (FISH) technique with a locus specific identifier (LSI) 13/21 probe, showed the formula: nuc ish (D13ZX2), (D21ZX3) [30].

The cytogenetic aetiology of chromosome 21 and the holoprosencephaly gene are discussed, focusing on the fact that cytogenetic and gene alterations could function synergically and coincide in their expression with the postulate of the multiple-hit process.