After 20 agonizing years, a mother and father have finally received answers regarding their daughter’s health. It shouldn’t take this long.

The Diagnosis

Their daughter was diagnosed with two very rare conditions. The first was Angelman syndrome. Angelman syndrome causes intellectual disability, delayed development, seizures, and impaired speech among other symptoms. This patient had all of the above. Secondly, she was diagnosed with P450scc deficiency. This is a side-chain cleavage disorder that results in adrenal insufficiency and sex reversal. While both of these conditions are rare on their own, it is even more rare that they occurred together. Researchers say that the odds of it happening again are very slim. This rarity is of course the reason for this patients extremely delayed diagnosis.

The patient’s P450scc deficiency was diagnosed after researchers uncovered that she had a recessive genetic condition called a uniparental disomy. This means that she had received 2 (impaired) copies of chromosome 15 from one of her parents and no copies of chromosome 15 from the other. This is what led to her hormonal issues, adrenal insufficiency, as well as her sex reversal. She presents as female; however, she has a Y-chromosome and testes.

How did the doctors finally uncover this diagnosis? It was through a combination of a multitude of different genetic tests.

Some of the tests these researchers used were-

• whole-exome sequencing
• in-vitro modeling for gene splicing
• microarray analyses

You can read the full paper explaining their methodologies here.

Ultimately, since different forms of technology will display different types of genetic changes, the right technologies have to be utilized in the right combinations in order to ensure the a complete and accurate diagnosis is provided to the patient.

Conclusions

What is the takeaway from this story? What lessons can be learned? Hopefully, as this story is publicized, medical professionals will be reminded that one test may not provide all of the answers. Just because they receive one negative result does not mean that they should dismiss the case. Likewise, just because they receive one positive does not mean they have uncovered all of the answers.

While the increased understanding of this patient’s genetic history will not actually change her care or treatment, it is still important because it provides this family answers. Finally.

Additionally, it will hopefully help to change the way scientists approach genetic analysis, especially for patients with numerous, complex symptoms and multiple disorders or disease states.

You can read more of this family’s story here.