An Overview of Coffin-Siris Syndrome

Coffin-Siris syndrome is a rare genetic condition that affects a number of body systems. Among the range of symptoms that characterize it are developmental disability, physical abnormalities of the pinky toes and fingers, as well as a distinctive, “coarse” facial features, among others. Infants and children with this condition often experience frequent respiratory infections and breathing problems and often do not gain weight at the proper rate. Only about 140 cases of Coffin-Siris syndrome have been recorded in the literature.

Symptoms

This condition causes a range of symptoms, many of which are easily seen and observed. The most frequent of these include:

• Intellectual Disability: Those with the condition may have mild to significant intellectual disabilities; this may present as disruptions in memory, communication, and learning.
• Delayed Motor Skills: Infants and toddlers may see mild to severe delays in the development of skills like walking or sitting.
• Underdevelopment of Fingers & Toes: The fifth or “pinky” toes and fingers may be underdeveloped.
• Absence of Nails on Fingers & Toes: These fingers and toes may not have nails.
• Speech Delay: Development of speech abilities may be delayed in those with Coffin-Siris syndrome.
• Distinctive Facial Features: These include wide nose, thicker eyelashes and brows, thick lips, wider mouth, and flat nasal bridge. The eyes may also appear abnormal.
• Extra Hair Growth: On the face and body, those with Coffin-Siris syndrome may have extra hair on the face and other parts of the body.
• Sparse Scalp Hair: Another hallmark of the condition is sparser hair on the scalp.

In addition, this condition sometimes leads to other issues:

• Small Head Size: Also known as microcephaly, a significant number of people with Coffin-Siris syndrome have a relatively smaller than average head.
• Frequent Respiratory Infections: Infants with this condition experience frequent respiratory infections and difficulty breathing.
• Feeding Difficulty: In infancy, feeding can become very difficult.
• Failure to Thrive: Related to the above, infants and toddlers may not gain weight or grow properly during important junctures.
• Short Stature: Those with the condition are often shorter in height.
• Low Muscle Tone: Coffin-Siris syndrome is also associated with “hypotonia,” or under-developed musculature.
• Loose Joints: Abnormally loose joints can also arise with this condition.
• Heart Abnormalities: Structural deformities of the heart and the great vessels have been observed in these cases.
• Brain Abnormalities: In many cases, this syndrome causes a smaller or absent cerebellum brain region.
• Abnormal Kidneys: Kidneys in those with Coffin-Siris syndrome may be “ectopic,” meaning they aren’t in the usual location.

The severity of the condition varies a great deal, and some symptoms are much more common than others.

Causes

Coffin-Siris syndrome arises due to abnormalities and mutation in any of the following genes: ARID1A, ARID1B, SMARCA4, SMARCB1, DPF2, or SMARCE1. The pattern of inheritance follows an autosomal dominant pattern; this means that it arises from a gene that doesn’t determine sex, with one error in coding being enough to cause the problem. Being genetic, the condition is inheritable, though largely, this disease has been most often observed arising for the first time in a family due to mutation. 

Diagnosis

Diagnosis of Coffin-Siris syndrome occurs after birth when doctors notice fifth finger and toe abnormalities as well as facial abnormalities. Deformities of this nature tend to become more pronounced with aging, and criteria for diagnosis are still evolving due to the rarity of the condition. Cognitive and developmental issues endemic to this disease are clinically significant signs of its progression.

Especially if a genetic history of Coffin-Siris syndrome is noted, doctors can also opt for molecular testing of the fetus prior to birth. This involves the use of ultrasound—a process of ultrasonography—to assess kidney or cardiac abnormalities. Alternately, forming fetal cells can be sampled and tested after 10 to 12 weeks of pregnancy. This kind of genetic examination is increasingly becoming available in specialized laboratories.

Following initial diagnosis, doctors may also call for further evaluation. In these cases, magnetic resonance imaging (MRI) may be used to detect abnormalities in the brain. Furthermore, X-ray can be used to assess the anatomy of affected fifth fingers or toes. Finally, echocardiograms—a type of MRI—may be used to detect anatomical differences in the heart and central veins.

Treatment

Since this disease has such a variety of symptoms, treatment depends on the specific presentation in the individual. Oftentimes, effective management of the condition requires coordination between medical professionals in several specialties. Pediatricians may have to work alongside orthopedists (those that treat disorders in bones, joints, and muscles), cardiologists (heart specialists), as well as physical therapists and geneticists.

Surgery may help in cases where there are significant facial, limb, or organ abnormalities. These are highly specialized procedures—the specific procedure very much depends on the severity of the case—but they can be helpful in taking on some of the physical manifestations of Coffin-Siris syndrome. For the respiratory problems that often accompany this condition, shunts or other surgeries may be required.

Outcomes for this disease improve with early intervention. Through physical therapy, special education, speech therapy, as well as social services, toddlers and children with this condition are better able to achieve their potential. With the right network of support and care, Coffin-Siris syndrome can be taken on.

Coping

Certainly, parents of children with Coffin-Siris syndrome, not to mention the children, themselves, face significant challenges. Alongside the physical ailments and effects, social stigmas can also add to the burden of this condition. Counseling and support groups can be helpful in facing these challenges.

A Word From Verywell

A diagnosis of Coffin-Siris syndrome is certainly difficult to receive, but it’s important to remember that help is there. With the right medical team, prognosis can certainly improve and symptoms can be managed. As the medical establishment learns more about it—and especially as procedures like genetic testing become more advanced—the situation will only improve. Research is ongoing, and with every discovery, with every refined procedure and approach, the future for those with this condition becomes brighter.