Ververi-Brady syndrome

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Ververi-Brady syndrome
Other namesVERBAS, QRICH1-related intellectual disability-chondrodysplasia syndrome
Adult-woman-with-VERBAS.jpg
Adult woman with VERBAS with characteristic facial features
Symptoms Mild intellectual disability, speech delays, microcephaly, chondrodysplasia, social interaction difficulties, variety of neurological symptoms
Usual onsetInfancy
Diagnostic method Genetic testing
TreatmentEducational supports if needed
FrequencyOnly 38 cases have been reported since discovery

Ververi-Brady syndrome (VERBAS) is a rare inherited disorder of unknown prevalence usually caused by a heterozygous mutation in the QRICH1 gene. Ververi-Brady syndrome was first described by Athina Ververi in 2018. The syndrome features a broad spectrum of symptoms, but all patients generally have mild chondrodysplasia, developmental delays, and mild dysmorphic facial features such as prominent nose. There has only been 38 reported cases.

Contents

History

In 2018, three unrelated children who had similar symptoms of developmental delays, skeletal abnormalities, and mild dysmorphic facial features. The first patient had an autism diagnosis and mild skeletal abnormalities but was otherwise normal. The second patient had poor growth in infancy, difficulty walking, tremors, difficulty speaking, and needed to be homeschooled due to academic difficulties. The third patient had microcephaly, poor growth, and was slow to learn how to walk but was able to attend mainstream school. All three of these patients had a variety of dysmorphic facial features that none of the patients shared except for a prominent nose, wide mouth, and thin upper lip. They were identified as having a de novo mutation on their QRICH1 gene. [1]

In 2019, 2 unrelated children were identified as having VERBAS and were found to have subtle chondrodysplasia. [2]

In 2021, Fohrenbach et al. described 4 unrelated patients with VERBAS. One patient, a three-year-old, developed nephroblastoma and died from complications, suggesting that increased cancer risk may be a part of the syndrome. [3]

In 2023, a 17-year-old girl was suffering from seizures and leukodystrophy. The girl had a history of minor developmental delays and was thought to have a perinatal brain injury resulting in mild right-side paresis. Her mother shared similar dysmorphic facial features, short stature, and distractable nature, causing them to be referred to a genecist. It was discovered that they both carried a novel QRICH1-related mutation and were diagnosed with VERBRAS. Previously, all cases of VERBRAS were de novo. [4]

Symptoms

Veriveri-Brady syndrome has a broad spectrum of variable symptoms, but symptoms that have been observed in all patients are:

Many patients have been observed as having mild intellectual disability, microcephaly, hypotonia, and autism. Patients may also have other neurological symptoms such as tremors, unsteady gait, poor reflexes, and seizures. A couple of patients had elevated levels of creatine kinase during infancy that later went down to normal.

It's suspected there may be an increased risk of cancer, genitourinary issues, and cardiac issues, but, due to the apparent rareness of VERBAS, it's unclear if there is any connection to VERBAS.

Causes

VERBAS is usually caused by a nonsense mutation on the QRICH1 gene that happens sporadically. In 2023 a new autosomal-dominant gene was identified that was passed down from a mother to her daughter.

Treatment

There is no cure for VERBAS. In almost all cases, people with VERBAS are able to attend mainstream school with or without supports. Due to the lack of research and rareness of the disorder, there are no developed treatments for it and all treatments are symptomatic.

References

  1. ↑ Ververi A (21 December 2017). "Phenotypic spectrum associated with de novo mutations in QRICH1 gene". Clinical Genetics. 93 (2): 286–292. doi:10.1111/cge.13096. PMID   28692176.
  2. ↑ Lui J (January 2019). "QRICH1 mutations cause a chondrodysplasia with developmental delay". Clinical Genetics. 95 (1): 160–164. doi:10.1111/cge.13457. PMC   6353565 . PMID   30281152.
  3. ↑ Fohrenbach M (January 2021). "QRICH1 variants in Ververi-Brady syndrome-delineation of the genotypic and phenotypic spectrum". Clinical Genetics. 99 (1): 199–207. doi: 10.1111/cge.13853 . PMID   33009816.
  4. ↑ Roddate M (22 May 2023). "Mother and Daughter with Short Stature, Microcephaly, Mild Dysmorphic Features, and Learning Disabilities Due to Ververi-Brady Syndrome Associated with a New Variant of the Gene". Am J Case Rep. 24: e939217. doi:10.12659/AJCR.939217. PMC   10215998 . PMID   37211757.
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