Molecular characterisation of a 3.5 Mb interstitial 14q deletion in a child with several phenotypic anomalies

Interstitial deletions of the long arm of chromosome 14 are infrequent. Molecular and clinical studies on patients with deletions involving 14q11.2-q21 have recently been reported.1 Most of these deletion patients share common clinical signs, such as midline defects of the central nervous system, feeding problems, growth abnormalities, hypotonia, developmental delay, mental retardation, and craniofacial anomalies.1 Here we present the phenotypic, cytogenetic, and molecular genetic findings of a 2½12 year old boy with a 14q12-q13.1 deletion. To our knowledge this is the second case described of a patient with a deletion of less than 3.5 Mb within chromosome bands 14q12-q13.1. Using the genomic sequence between markers D14S1060 and D14S286, we have constructed a transcription map of the genomic interval deleted in our patient. Our proband (fig 1) is the 40 week product of a second, uncomplicated pregnancy and delivery. Maternal age was 27 years. Birth weight was 4435 g (>90th centile), length 55 cm (>90th centile), and head circumference 34 cm (10th-25th centile). Apgar score was 7/9/10. The neonatal period was complicated by pneumonia, treated with parenteral antibiotic therapy over 10 days. Besides relative microcephaly, hypertelorism, epicanthic folds, a long and flat philtrum, hypodontia, laterally placed, hypoplastic mamillae, second degree hypospadias, bifid scrotum, and bilateral cryptorchidism were noticed. Cranial ultrasound was normal; ultrasound of the kidneys and pelvic region showed bilateral second degree hydronephrosis, and both testes were visible in the inguinal region. Screening for connatal infections (toxoplasmosis, rubella, cytomegalovirus, and parvovirus B19) was negative. Psychomotor development was severely impaired from early infancy. Lack of vision was evident at 3 months and, apart from head control, no gain of motor milestones or social contact was achieved until the age of 29 months. Muscle tone of the trunk was decreased while it was increased and dystonic in the upper and …