Chromosome 1q42 deletion and agenesis of the corpus callosum

We read with interest the report of Gentile et al. [2003] describing a 24-year-old woman with a de novo terminal deletion of chromosome 1 and partial agenesis of the corpus callosum. We have recently seen a family in which an interstitial deletion of chromosome 1q42 segregates with complete absence of the corpus callosum. These observations suggest that a gene important in the development of this structure is situated at 1q42. The male proband was delivered at 35 weeks by caesarean because of polyhydramnios. A karyotype performed by amniocentesis for advanced maternal age was reported as normal. Apgars were 6 and 8 at 1 and 10 min respectively. He weighed 2.94 kg (90th centile) and had a head circumference on the 50th centile. He experienced some respiratory distress necessitating nasal oxygen supplementation, which was discontinued on day 6. The child was considered nondysmorphic but was noted to have a small penis and underwent investigation of his hypothalamic-pituitary axis. Cranial sonogram showed isolated absence of the corpus callosum, which was later confirmed on MRI (Fig. 1). Endocrinological and other routine investigations as well as ophthalmological assessment and a renal sonogram were normal. Aged 8 months, he underwent a right-sided orchidopexy. When last reviewed at the age of 15 months, he had an umbilical hernia, which was easily reducible. At this time, he could cruise around furniture adeptly, was babbling and appeared interested and alert. His head circumference was 46.5 cm (25th centile), weight 10 kg (25th centile) and length 73 cm (2nd centile). G banding at 550-band resolution demonstrated an interstitial deletion at chromosome 1q42. Fluorescent in situ hybridization studies using a probe for the 1q subtelomeric region showed two signals, and whole chromosome 1 painting identified no translocated material. The proband’s brother was born at term weighing over 4 kg. His early developmentwas considered normal, althoughhe did notwalk until 18months of age.He required repair of a coronal hypospadias at age 4 years. By that time, it was obvious he had speech and language delay. At age 8 years, he was considered to have mild to moderate learning difficulties and expressive language delay. At age 9 years, he was assessed to have a reading age of 5 years. He was considered to exhibit some oppositional and impulsive behaviors. Results of the original karyotype taken the previous year were reported as normal, but re-analysis in light of his brother’s diagnosis showed the same chromosome 1q42 deletion. On examination, he is nondysmorphic with a head circumference of 51.5 cm (25th centile), weight 32 kg (25th–50th centile) and height 132.5 cm (10th centile). He has an absent corpus callosum on cranial MRI. The mother of these two boys was born after a normal pregnancy. Beyond a tonsillectomy at age 6 years, she had never been referred to medical services. Unlike her academically successful brother and parents, she left school at age 16yearsafter completing only two state examinations. Shewas subsequently employed as a childcare assistant and a hospital care worker. At age 40 years, she is 157 cm tall (10th centile), 90.5 kg inweight (>97th centile) and has a head circumference of 56 cm (90th centile). She is nondysmorphic and physical examination is unremarkable. She carries the samedeletion as seen in her sons. She also has an absent corpus callosum. Her parents were unavailable for examination. All three individuals in this family have a 1q42 deletion and complete agenesis of the corpus callosum. The mother of the