Skraban-Deardorff Syndrome

Skraban-Deardorff syndrome, also known as WDR26-related intellectual disability, is a rare genetic disorder characterized by developmental delay, intellectual disability, seizures, neurological differences and subtle facial differences.

The syndrome was recently discovered by identifying 15 unrelated individuals who have mutations in a particular gene and finding that all share a similar cluster of symptoms.

Skraban-Deardorff syndrome is caused by mutations in the WDR26 gene.

In the individuals identified to date, these are de novo mutations. This means that the mutations are not inherited from either parent, but instead are random mutations that occur newly in a child during early development.

The mutations are also heterozygous, which means that only one copy of an individual’s two copies of the WDR26 gene has the mutation.

The symptoms of Skraban-Deardorff syndrome vary among individuals. Not every person with the syndrome exhibits all of the symptoms or exhibits them in the same way. Symptoms include:

Developmental delay and intellectual disability

• People with Skraban-Deardorff syndrome have varying degrees of developmental delays and intellectual disabilities, ranging from mild to severe.
• Speech delays have been seen in all individuals and about 25 percent had no speech at the last time they were assessed (two at age 4, one at age 5 and one at age 8).
• Delays in the development of motor skills are typical. Individuals in the initial sample group were delayed in sitting and crawling, but started to walk between 17 months and 3 years of age. Most walk with a wide-based, stiff-legged gait.

Behavior

• Some individuals with the syndrome have stereotypical movements (repetitive, purposeless movements). Most are described as being happy and socially engaging.
• Some people with Skraban-Deardorff syndrome have also received a diagnosis of autism spectrum disorder.

Neurological differences

• All individuals in the initial sample group had a history of seizures. However, most were mild.  Some seizures were triggered by fever (febrile seizures). Those with non-febrile seizures (not related to fever) experienced them in childhood, with the first occurrences ranging from infancy to 7 years of age. Some had received treatment with antiepileptic medications, which typically controlled the seizures.
• Minor structural brain malformations have been identified in some people (9 of 13 individuals).
• Decreased muscle tone (hypotonia) was seen in approximately75 percent of the initial sample group.

Facial differences

People with Skraban-Deardorff syndrome typically share a set of subtle facial characteristics, though not every individual with the syndrome exhibits all of them. These characteristics include:

• Prominent upper lip and upper jawbone
• Wide mouth
• Abnormal gums
• Widely spaced teeth
• Mildly coarse facial features
• Broad nasal tip

If symptoms suggest Skraban-Deardorff syndrome, specific testing for WDR26 can be performed.  However, diagnosis is typically made with whole exome sequencing, a genetic test that looks at the sequencing of the more than 20,000 protein-coding genes in the individual’s DNA.

Typically, Skraban-Deardorff syndrome is caused by de novo (spontaneous rather than inherited) mutations in the WDR26 gene, and it is useful to confirm that neither parent carries the change.

Currently, there is no specific treatment for Skraban-Deardorff syndrome. Care focuses on the individual’s symptoms. The medical team typically includes a genetic specialist, a neurologist and a developmental pediatrician, with other specialists involved as symptoms warrant. Early therapy is encouraged (physical, occupational, speech therapy) to ensure that the child achieves to the best of their abilities.

Because Skraban-Deardorff syndrome has only recently been identified, the long-term outlook for patients is not yet fully known.

In general, patients with developmental delay and intellectual disability benefit from support and therapy, which can improve the quality of a child’s life. Seizures can be treated with antiepileptic medications.

Annual follow-up visits with an appropriate team of specialists are recommended for children with Skraban-Deardorff syndrome. Regular monitoring allows the medical team to adapt therapeutic treatment to the child’s changing needs. The care is geared to providing the highest possible quality of life and addressing any symptoms that cause discomfort or put the child’s health at risk.

Skraban-Deardorff syndrome was discovered at Children's Hospital of Philadelphia (CHOP) and the experts at CHOP are leaders in research on the syndrome.

CHOP provides comprehensive clinical care, diagnostic testing, and state-of-the-art, multidisciplinary care to infants, children and adolescents living with genetic conditions like Skraban-Deardorff syndrome.

For parents of children with Skraban-Deardorff syndrome and other genetic conditions, CHOP provides training on special care needs, as well as genetic counseling to explain the risk of having another child with the condition.

Reviewed by: Cara M. Skraban, MD
Date: Sept. 18, 2018