Individuals with Lichtenstein-Knorr syndrome possess a limited range of inherited pathogenic mutations in the SLC9A1gene (~4 mutations described to date).
The SLC9A1gene produces a protein on the surface of most cell types in the body that helps regulate their intracellular acid-base (pH) balance. Maintenance of intracellular pH homeostasis is important for the development and function of brain cells and neural circuits as well as the proper functioning of cells in other tissues. However, defects in the functioning of tissues/organs other than brain have not been documented to date, suggesting the possibility of compensatory molecular mechanisms to control pH homeostasis in those tissues. However, this warrants further investigation.
Usually, SLC9A1-related conditions are caused by a single ‘spelling’ variation in the gene, which means the message is not read or received properly, resulting in the production of a defective, non-functional protein. SLC9A1-related conditions are genetic conditions. This means that the condition was not caused by anything the mother or father did before the baby was conceived, during pregnancy or birth, or after the baby was born. SLC9A1-related conditions are extremely rare, although the precise prevalence of the disease is currently unknow. As the disorder is autosomal recessive (that is, the gene is located on one of the 22 pairs of numbered, non-sex chromosomes in humans—in this case chromosome 1—as opposed to the sex chromosomes X and Y), developing the disorder requires inheriting an abnormal gene from both parents and can affect males and females equally.
What is needed to confirm the diagnosis of SLC9A1-related syndrome?
The diagnosis of SLC9A1-related syndrome is confirmed by performing genetic testing in an affected individual, which enables the detection of a disease-causing change in the SLC9A1 gene.
There are two possible strategies to identify a SLC9A1 change:
• If the individual’s characteristics are not sufficient to raise the suspicion of SLC9A1-related syndrome (for example, because they overlap with the characteristics observed in other genetic disorders), the DNA sequence of multiple genes, including SLC9A1, will be analysed using a multi-gene panel or exome sequencing.
• If the individual’s characteristics raise the suspicion of SLC9A1-related syndrome, only the DNA sequence of the SLC9A1 gene will be analysed.
The genetic testing can be arranged by a clinical geneticist and involves the collection of a sample of blood or saliva from the affected individual (and eventually the parents). Analysing the DNA of the patient and comparing it with the parents’ DNA may facilitate the detection of a disease-causing change in the SLC9A1 gene that is not present in the healthy parents (i.e. a “de novo” change).
SLC9A1