The cytogenetics of mammalian autosomal rearrangements.

Summary:  Purpose: We analyzed databases on chromosomal anomalies and epilepsy to identify chromosomal regions where abnormalities are associated with clinically recognizable epilepsy syndromes. The expectation was that these regions could then be offered as targets in the search for epilepsy genes.



Methods: The cytogenetic program of the Oxford Medical Database, and the PubMed database were used to identify chromosomal aberrations associated with seizures and/or EEG abnormalities. The literature on selected small anomalies thus identified was reviewed from a clinical and electroencephalographic viewpoint, to classify the seizures and syndromes according to the current International League Against Epilepsy (ILAE) classification.



Results: There were 400 different chromosomal imbalances described with seizures or EEG abnormalities. Eight chromosomal disorders had a high association with epilepsy. These comprised: the Wolf–Hirschhorn (4p-) syndrome, Miller–Dieker syndrome (del 17p13.3), Angelman syndrome (del 15q11-q13), the inversion duplication 15 syndrome, terminal deletions of chromosome 1q and 1p, and ring chromosomes 14 and 20. Many other segments had a weaker association with seizures. The poor quality of description of the epileptology in many reports thwarted an attempt to make precise karyotype–phenotype correlations.



Conclusions: We identified certain chromosomal regions where aberrations had an evident association with seizures, and these regions may be useful targets for gene hunters. New correlations with specific epilepsy syndromes were not revealed. Clinicians should continue to search for small chromosomal abnormalities associated with specific epilepsy syndromes that could provide important clues for finding epilepsy genes, and the epileptology should be rigorously characterized.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1528-1157.2002.19498.x

Chromosomal abnormalities and epilepsy: a review for clinicians and gene hunters.

Clinical Atlas of Human Chromosomes

We report on an individual with severe mental retardation, seizures, microcephaly, unusual face, scoliosis, and cleft feet and cleft right hand. The chromosomal study showed a proximal interstitial deletion 7q (q11.23q22). From our review of the literature, 11 patients have been reported with ectrodactyly (split hand/split foot malformation) and proximal/intermediate interstitial deletions or rearrangements of 7q. The critical segment for ectrodactyly seems to be located between 7q21.2 and 7q22.1. This malformation is present in 41% of the patients whose deletion involves the critical segment. 37 refs., 3 figs., 1 tab.

Ectrodactyly and proximal/intermediate interstitial deletion 7q

Terminal deletions of the long arm of chromosome 7 are well known and are frequently associated with hypotelorism or holoprosencephaly due to the involvement of the SHH gene located in 7q36.3. These deletions are easily detectable with routine subtelomeric MLPA analysis. Deletions affecting a more proximal part of 7q36, namely bands 7q36.1q36.2 are less common, and may be missed by subtelomeric MLPA analysis. We report a 9-year-old girl with a 5.27 Mb deletion in 7q36.1q36.2, and compare her to literature patients proposing a phenotype characterized by mental retardation, unusual facial features, renal hypoplasia and long QT syndrome due to loss of the KCNH2 gene. These characteristics are sufficiently distinct that the syndrome may be diagnosed on clinical grounds.

Delineation of the phenotype associated with 7q36.1q36.2 deletion: Long QT syndrome, renal hypoplasia and mental retardation

Verma RS, Conte RA, Sayegh SE, Kanjilal D. The interstitial deletion of bands q33–35 of long arm of chromosome 7: a review with a new case report. Clin Genet 1992:41: 82–86.



Interstitial or terminal deletion resulting in partial monosomy of various segments of the long arm of chromosome 7 was first recorded over two decades ago. Since then, a number of reports have correlated the severity of clinical manifestations with the length of the deletion involved. However, difficulty remains in defining a so-called “distinct syndrome”. We present a new case with the shortest interstitial deletion of the long arm of chromosome 7 bands q33–35, i.e. 46,XX,del(7)(pter q33::q35 qter). A 4-year-old black female was referred for cytogenetic evaluation due to neurodevelopmental delay. Pertinent physical examination at birth was cleft lip and cleft palate which required corrective surgery. At 2 years of age, a myringotomy tube was inserted for repeated ear infection and a hearing aid was required for conductive deafness. Neurological examination revealed poor eye contact, and severe mental and motor retardation. We reviewed 21 cases of a partial interstitial deletion of varied segments of the long arm of chromosome 7, but we were unable to establish a definite relationship with the deletion of various 7q segments with any specific clinical manifestations.

Debasis Kanjilal

Papers

The interstitial deletion of bands q33-35 of long arm of chromosome 7: a review with a new case report.