ABCD Syndrome - History

History

Dutch ophthalmologist Petrus Johannes Waardenburg (1886–1979) brought about the idea of Waardenburg syndrome when he examined two deaf twins. Waardenburg decided to define the syndrome with the six major symptoms that patients most commonly had.

• He defined “lateral displacement of the medial canthi combined with dystopia of the lacrimal punctum and blepharophimosis” referring to people with broader and flatter nasal bridges, which in turn leads to folds in the skin that cover the inner corners of the eye.
• Secondly, people who are born with a “prominent broad nasal root,” have a widened area between the eyes, causing them to have a flatter and wider face, along with eyes farther apart than normal.
• Thirdly, “hypertrichosis of the medial part of the eyebrows” is present, meaning excessive hair growth in the patients’ eyebrow region, most likely leading to a unibrow.
• The fourth symptom, “white forelock,” was commonly seen as depigmented strands of hair
• “Heterochromia iridis” indicates that the patient has two different colored eyes or two colors in the same eyes.
• “Deaf-mutism”: People with the disorder are both deaf and mute.

When scientists further investigated the syndrome, they realized that patients exhibited a wider range of symptoms of this disease in different combinations. This helped them distinguish forms of Waardenburg syndrome. Their evaluation consisted of specifying Waardenburg syndrome type I (WS1), type II (WS2), type III (WS3), and type IV (WS4).

In 1995, a case study was performed of a Kurdish family. Scientists completed a molecular analysis with DNA strands of the patients diagnosed with ABCD syndrome. Their task was to scan the sequences to find a mutation in the EDNRB gene, one of the most important protein-coding genes. When they completed the scan they “found a homozygous C to T transition resulting, at the amino acid level, in a premature stop codon.” Then, they went back and defined that Shah-Waardenburg syndrome consisted majorly of “mutations in the ENDRB or END3 gene,” along “with SOX10 mutations.” Therefore, the researchers confirmed that ABCD syndrome was a form of Shah-Waardenburg syndrome. The genetic tests that they performed on the patients DNA helped in identifying the appropriate diagnosis.

In 2002, Whitkop and other scientists examined patients born with white hair, some black locks, and depigmented skin; he diagnosed them as having black lock albinism deafness syndrome (BADS). Those who were closely working with this case suggested that it was an autoimmune disorder rather than a genetic defect. However, soon after, they had a patient who was one of fourteen children of Kurdish parents. The pedigree they examined revealed autosomal-recessive inheritance which led to cell migration of the neurocytes in the gut and, therefore, they redefined the syndrome as ABCD syndrome. This revealed “a homozygous nonsense mutation in the EDNRB gene” meaning that ABCD syndrome was not a separate entity but rather the same as Shah-Waardenburg syndrome.