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Interstitial deletions or apparently balanced translocations involving bands 1p31 and 1p32 in the short arm of chromosome 1 are rarely described chromosomal imbalances. To our knowledge, there have been six cases documented to date. Five of these cases, where the NFIA gene is involved, show complex central nervous system malformations and in some cases urinary tract defects. We report another case of a microdeletion with involvement of the NFIA gene in the short arm of chromosome 1 (del(1)(p31.3p32.2)) with, amongst other features, hypoplasia of the corpus callosum, ventriculomegaly, and dysmorphic features. A microdeletion 1p31.3p32.2 which includes the NFIA gene is associated with hypoplasia of the corpus callosum, ventriculomegaly, and dysmorphic features.

Alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome; OMIM 203550) is a very rare genetic disorder with distinct features. To our knowledge, there have been four cases documented to date. In addition, another three patients, previously described as having IFAP syndrome (OMIM %308205), may also have ACD syndrome. We report on one patient with short stature, total alopecia, ichthyosis, photophobia, seizures, ectrodactyly, vertebral anomalies, scoliosis, multiple contractures, mental retardation, and striking facial and other features (e.g. microdolichocephaly, missing eyebrows and eyelashes, long nose, large ears) consistent with ACD syndrome. Results of laboratory testing in the literature case reports were normal, although in none of them, array-CGH (microarray-based comparative genomic hybridization) analysis was performed. In conclusion, the combination of specific features, including total alopecia, ichthyosis, mental retardation, and skeletal anomalies are suggestive of ACD syndrome. We propose that children with this syndrome undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investigation, psychological testing, management of dermatologic and orthopedic problems, and genetic counseling.

Gomez-Lopez-Hernandez syndrome is a very rare genetic disorder with a distinct phenotype (OMIM 601853). To our knowledge there have been seven cases documented to date. We report on an additional male patient now aged 15 8/12 years with synostosis of the lambdoid suture, partial scalp alopecia, corneal opacity, mental retardation and striking phenotypic features (e.g., brachyturricephaly, hypertelorism, midface hypoplasia and low-set ears) consistent with Gomez-Lopez-Hernandez syndrome. In early childhood the patient demonstrated aggressive behavior and raging periods. He also had seizures that were adequately controlled by medication. Magnetic resonance imaging (MRI) revealed rhombencephalosynapsis, i.e., a rare fusion of the cerebellar hemispheres, also consistent with Gomez-Lopez-Hernandez syndrome. In addition a lipoma of the quadrigeminal plate was observed, a feature not previously described in the seven patients reported in the literature. Cytogenetic and subtelomere analyses were inconspicuous. Microarray-based comparative genomic hybridization (array-CGH) testing revealed five aberrations (partial deletions of 1p21.1, 8q24.23, 10q11.2, Xq26.3 and partial duplication of 19p13.2), which, however, have been classified as normal variants. Array-CGH has not been published in the previously reported children. The combination of certain craniofacial features, including partial alopecia, and the presence of rhombencephalosynapsis in the MRI are suggestive of Gomez-Lopez-Hernandez syndrome. Children with this syndrome should undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investingation, psychological testing, management of behavioral problems and genetic counseling.

Feeding disorders in ex-prematures do exist and may constitute a major challenge to their families' well being. A cases series of 86 ex-prematures with severe feeding disorders was analysed regarding co-morbidity, response to therapy and the long-term outcome after treatment. These children with a gestational age of <37 weeks had been referred for hospital rehabilitation because of severe feeding disorders, defined as tube feeding or average feeding times of more than 30 minutes. Behavioural therapy was the key element of the treatment. Ex-prematures accounted for 86/266 patients admitted for treatment of feeding disorders between 1995 and 2004. Whereas only 40.8% of these had cerebral palsy, 51.1% had a diagnosis of mental retardation and 87% had interaction problems. Response to treatment up to discharge was achieved in 61.6%. Univariat analyses showed that tube feeding at admission and swallowing difficulties were the best predictors of failure to respond to the intervention. Long-term follow-up data that were collected for 53 of the 86 children with similar initial response to therapy (64.2%) compared to children with no follow-up data (57.6%). Success of therapy after discharge was maintained in 94.1%; however, 25% of the children with normal BMI's at discharge and sustained success of therapy fell below the 3rd BMI percentile. Cerebral palsy, mental retardation and interaction problems appear to be important risk factors for severe feeding disorders in ex-prematures. A therapeutic intervention based on behavioural therapy achieved sustained success in almost two thirds of the children.

We have investigated the chromosome abnormalities in a female patient exhibiting a severe cognitive disability associated with complete agenesis of the corpus callosum and microcephaly. The patient carries a balanced de novo translocation t(2;14)(p22;q12), together with a neighbouring 720 kb inversion in chromosome 14q12. By combined fluorescence in situ hybridisation and Southern hybridisation, the distal inversion breakpoint on chromosome 14 was mapped to a region harbouring genes and ESTs derived predominantly from brain tissue. RT-PCR studies indicated that these transcripts comprise the 3' ends of novel splice variants of the winged helix transcription factor FOXG1B (also referred to in previous studies as FOXG1A and FOXG1C, as well as Brain Factor 1), the mouse orthologue of which is essential for normal development of the telencephalon. Analysis of these novel FOXG1B transcripts indicated that they are all disrupted by the breakpoint in the patient. Moreover, we have identified novel orthologous Foxg1 transcripts in the mouse and other vertebrates, which validates the functional importance of these variants and provides a direct genetic link between the patient phenotype and that of the heterozygous Foxg1 knockout mice. These results, together with previously published studies on patients with similar disorders and proximal 14q deletions, strongly suggest that several disorders associated with malformations of the human brain may be directly caused by mutations or alterations in the FOXG1B gene.