A look into Korea's first-and-only documented case of Gabriele-de Vries syndrome (GADEVS, MIM #617557).
A 7-month-old girl was born at 39 gestation weeks with a body weight measurement of 3,140g (-.15 standard deviation [SD]) at birth.
Developmental delay (DD) and subtle facial dysmorphism (listed below) were present:
- facial asymmetry
- low-set ears
Parents both Korean, with no family history of developmental delays or abnormalities.
Identification of a likely pathogenic YY1 variant is suspected, expanding the phenotypic spectrum of Gabriele-de Vries syndrome.
Regarding prevalence, there have only been ten cases documented in medical literature of the syndrome.
Patient was brought to hospital specializing in DD, with the following results:
- Chromosome (karyotype): 46, XX
- CMA: Normal
- Tandem MS: Normal
- Abdominal US, echocardiogram: Normal
- Bayley-III assessment: Mild degree of global developmental delay, especially in gross motor function.
As a next generation sequencing (NGS) technique, whole exome sequencing (WES) is able to identify genomic variants within undiagnosed syndromic cases in an efficient, cost-effective way.
A WES test was requested by the patient’s family.
The entirety of the patient’s proband WES test was performed at 3billion, Inc.
- 98.8% of base positions covered at >=20X
- Utilized xGen Exome Research Panel v2 (Integrated DNA Technologies)
- Aforementioned abnormalities (DD, facial dysmorphism) were employed as filtering indices
The WES test successfully identified a novel heterozygous missense variant in the YY1 gene, further validated by Sanger sequencing.
- Gene: YY1
- Position: 14-100743912-A-G
- HGVS nomenclature: NM_003403.4: c.1220C>T (p.His407Arg)
- Allelic origin: de novo
Diagnosis and Current Status
The patient was successfully diagnosed with Gabriele-de Vries syndrome in infancy.
Due to diagnosis during infancy, access to intensive rehabilitation therapy is eased. Regarding the patient’s cognitive function, this allows it to not worsen further.
This is the first report of Gabriele-de Vries syndrome within the South Korean population, which could expand the clinical and molecular spectra of the syndrome.
The patient currently attends and undergoes rehabilitation treatments twice a week focused on occupational therapy and neurodevelopment, as well as daily living tasks.
Below is insight from Jinsup Kim, M.D., Clinical Associate Professor of Hanyang University College of Medicine, who is also situated in Korea:
Why was a genetic disease suspected initially?
It was observed that the patient had developmental delay and facial dysmorphism.
Were there any candidates for possible diseases prior to the WES test?
No diseases fit, so there were no candidates. This is a primary reason why I chose to utilize WES testing.
Prior to WES testing, what techniques were used in an attempt to diagnose the patient?
Simultaneous execution of microarray.
Following WES testing, could you provide insight as to what was confirmed?
De novo via parental examination was confirmed. Highly likely based on symptoms.
Regarding the patient's follow-up, how are they currently doing?
The patient is currently undergoing neurological therapy and rehabilitation, as well as hearing tests, regularly.
Although there have been many advances in the area of rare disease diagnosis, there are still many difficulties. What aspects of rare disease diagnosis can be improved?
Efforts to find the basis for judgements about the revealed mutations. Additionally, continuous follow-up and feedback of and from undiagnosed patients are [should be] required.