Lamb-Shaffer Syndrome (LAMSHF)

What is Lamb-Shaffer syndrome?

Lamb-Shaffer syndrome (LAMSHF) is a rare genetic disorder. It can result in developmental delays, speech abnormalities, intellectual disability and, sometimes, behavioral differences. It can also cause mild changes in facial or skeletal development.

Where does Lamb-Shaffer syndrome get its name?

Lamb-Shaffer syndrome gets its name from two of the researchers who discovered it in 2012. Since then, their findings have been confirmed and extended.

How common is Lamb-Shaffer syndrome?

Experts don’t know exactly how many people have Lamb-Shaffer syndrome, but the condition is rare. To date, fewer than 100 cases have been reported in peer-reviewed medical literature.

What causes Lamb-Shaffer syndrome?

Lamb-Shaffer syndrome is a genetic disorder. This means it happens because of a change (mutation) in a specific gene. LAMSHF happens when someone has a pathogenic (damaging) variant in one of the two copies of the SOX5 gene. (People without LAMSHF have two normal copies of that gene.) The SOX5 gene is responsible for protein synthesis and plays a role in controlling the development of certain types of cells in your brain and body.

Most people with LAMSHF have this condition as a result of a newly occurring (also called de novo) mutation. In other words, the biological parents have two normal copies of the SOX5 gene in all of the cells in their bodies.

About 15% of people with LAMSHF have one parent who has one copy of a mutated SOX5 gene in some of their reproductive cells. But most of their reproductive cells contain two normal copies of the SOX5 gene. Because the mutation isn’t present in most other cells and tissues, the parent doesn’t have LAMSHF.

There are rare instances where LAMSHF is inherited from an affected parent. People with LAMSHF have a 50% chance of passing the condition down to their children.

What are the symptoms of Lamb-Shaffer syndrome?

Usually, the first signs of LAMSHF are developmental delays in speech and motor skills (like walking or sitting independently). Infants may also have low muscle tone (hypotonia).

Children and adults with LAMSHF may have:

• Delayed speech development.
• Shortened attention span.
• Hyperactivity.
• Intellectual disability.
• Uncontrollable rhythmic, repetitive movements (stereotypies).
• Social isolation.
• Temper tantrums.
• Various eye issues such as strabismus (crossed eyes) or refractive errors (such as nearsightedness or astigmatism).

Fewer than 1 in 10 children with LAMSHF also have seizures. People with LAMSHF may also show facial or skeletal differences, such as:

• Broad nose.
• Prominent forehead (frontal bossing).
• Small chin or jaw.
• Strabismus (crossed eyes).
• Thin upper lip or irregularly full lips.
• Irregular joining (fusion) in one or more neck bones.
• Forward rounding in the spine (kyphosis).
• Irregular curve in their spine (scoliosis).

How is Lamb-Shaffer syndrome diagnosed?

Healthcare providers use genetic testing to diagnose LAMSHF. Providers may recommend genetic testing for children who have delays in early motor and language development or mild differences in facial or skeletal features.

Can you diagnose Lamb-Shaffer syndrome during pregnancy?

Healthcare providers don’t routinely test for Lamb-Shaffer syndrome during pregnancy. If the birthing parent or a close family member is a carrier for the SOX5 gene mutation or has LAMSHF, providers may test for the condition during pregnancy.

How is Lamb-Shaffer syndrome treated?

There’s no specific treatment for Lamb-Shaffer syndrome. Treatment focuses on helping people improve their quality of life. It may include:

• Behavioral management therapy to reinforce appropriate or desired behaviors and help reduce unwanted behaviors.
• Individualized education program (IEP) or special education services to support children and teens with schooling.
• Speech therapy to help people improve their communication and speech.
• Physical therapy, including strengthening exercises or walking aids, to improve posture and physical function in people with spinal problems.
• Genetic counseling to help parents understand their child’s clinical condition and update the family regarding new information about LAMSHF.
• Ophthalmological evaluations to assist in the care of possible eye-related issues such as refractive errors or strabismus.
• Neurological evaluations to assist in the care of possible neurological issues such as seizures or gait abnormalities.
• Orthopaedic evaluations to assist in the care of possible orthopaedic issues like scoliosis.

How do I know if my future children are at risk for Lamb-Shaffer syndrome?

If you or a family member has a known SOX5 gene mutation, you may want to seek genetic counseling. A genetic counselor helps you understand the chances of having children with Lamb-Shaffer syndrome. They’ll also talk with you about what LAMSHF would mean for you and your child.

What is the prognosis for Lamb-Shaffer syndrome?

Based on current information, Lamb-Shaffer syndrome doesn’t seem to affect life expectancy. But the outlook for quality of life with LAMSHF can vary.

People with Lamb-Shaffer syndrome may have varying abilities to function on their own. Depending on their intellectual abilities, they may need lifelong support from a caregiver.

What else should I ask my doctor?

You may also want to ask your healthcare provider:

• What are the signs of Lamb-Shaffer syndrome?
• What tests might my child need to diagnose Lamb-Shaffer syndrome?
• What are the treatment options?
• What are the chances that I’ll have another child with Lamb-Shaffer syndrome?

A note from Cleveland Clinic

Lamb-Shaffer syndrome is a rare genetic disorder. It causes developmental delays, intellectual disability and changes in facial features. People with LAMSHF may also have spinal problems. There’s no cure for LAMSHF. People with the condition may have speech therapy, behavioral management therapy or special education plans to help improve their function and quality of life. LAMSHF doesn’t affect life expectancy, but it may affect a person’s ability to function on their own.