Verheij syndrome is a rare genetic condition caused by changes to a specific gene that is present from birth. It can affect many different parts of the body. Its rarity makes estimating the number of affected people difficult, and some individuals with mild symptoms may not be diagnosed.
Genetic Origins of Verheij Syndrome
Verheij syndrome arises from a mutation or deletion affecting the PUF60 gene, located on the long arm of chromosome 8. The PUF60 gene provides instructions for making a protein involved in RNA splicing, a process for ensuring genes are expressed correctly. This protein’s function is especially active during early embryonic development.
A mutation in the PUF60 gene results in haploinsufficiency. This occurs when one of the two gene copies in each cell is inactivated or missing. The remaining functional copy cannot produce enough protein for normal development, leading to the features of Verheij syndrome.
The condition follows an autosomal dominant inheritance pattern, so a mutation in only one copy of the gene causes the disorder. While it can be inherited from a parent, most cases result from a de novo (new) mutation. This means the genetic change occurs spontaneously, without any prior family history of the condition.
Common Signs and Symptoms
Developmental delays are common, affecting milestones like sitting, crawling, and walking. Intellectual disability, ranging from mild to moderate, is also a feature, along with frequent speech and communication difficulties.
Distinctive facial characteristics are often associated with the syndrome, though they can be subtle. These may include:
- A small head (microcephaly)
- A prominent forehead
- Arched eyebrows
- A short or bulbous nose
- A thin upper lip
Some individuals may also have skin tags on the face or neck.
Skeletal abnormalities are present in many cases. Joint laxity (“loose joints”) is a common finding and may lead to dislocations. Curvature of the spine (scoliosis), other vertebral anomalies, and short stature are also reported.
Other health issues can be part of the syndrome. Congenital heart defects are seen in a significant number of individuals, with issues ranging from valve defects to more complex problems like Tetralogy of Fallot. Eye abnormalities are also common, including coloboma (a gap in an eye structure). Kidney and urinary tract anomalies, such as a missing or horseshoe-shaped kidney, can also be present.
The Diagnostic Process
The diagnostic process often begins when a healthcare provider observes a combination of developmental delays and specific physical traits. A clinical geneticist may then perform a thorough physical examination and review the individual’s medical and family history.
While a clinical evaluation is the first step, it cannot provide a definitive answer. The diagnosis must be confirmed through molecular genetic testing, which involves analyzing a blood sample to look for a pathogenic variant in the PUF60 gene.
Tests like whole exome sequencing, which examines the protein-coding regions of all genes simultaneously, are often used to identify the causative mutation. Finding a harmful variant in PUF60 confirms the diagnosis of Verheij syndrome and is useful for distinguishing it from other syndromes that may have overlapping features.
Management and Support Strategies
There is no cure for Verheij syndrome, so treatment focuses on managing specific symptoms and supporting the individual’s development. This requires a coordinated, multidisciplinary team of specialists tailored to the person’s needs.
Developmental support is a primary component of the management plan. Physical therapy can help with motor skills and joint laxity, while occupational therapy assists with daily living activities. Speech and language therapy is used to address communication challenges, and early intervention services are beneficial for addressing developmental delays from a young age.
Regular monitoring by medical specialists is necessary to manage associated health conditions. This team may include:
- A cardiologist to monitor heart defects
- An ophthalmologist to manage vision problems or eye abnormalities
- A nephrologist to monitor kidney function
- An orthopedic specialist to provide care for skeletal issues like scoliosis
- An endocrinologist to monitor growth