Overview

What is nager syndrome?

Nager syndrome (acrofacial dysostosis) is a very uncommon genetic disorder that affects less than one in every one million people. This condition affects the bones and tissues of the face, arms and hands, and, in rare cases, legs and feet. It is present at birth and results in distinct facial characteristics such as underdeveloped cheekbones, downward-sloping eyes, and a tiny jaw. This syndrome is related to Treacher-Collins syndrome, but it also has limb difficulties (such as thumb and lower arm deformities¹ and is frequently associated with a cleft palate.

Early in pregnancy, the development of the cheekbones, eye sockets, and jaw is interrupted, resulting in these distinct traits.

What causes nager syndrome?

Nager syndrome is generally caused by alterations (mutations) in the gene SF3B4.² This gene is significant because it aids in the process of producing proteins from our genetic code, which is required for optimal development during pregnancy. This gene influences the development of the first and second pharyngeal arches during early pregnancy. Some families pass it along from generation to generation. This can occur in two ways.

• Autosomal dominant inheritance means that the syndrome can be caused by a single copy of the defective gene from either parent
• Autosomal recessive inheritance means that the condition develops only if a kid receives two copies of the defective gene, one from each parent

However, the majority of Nager syndrome instances are sporadic, meaning they are not inherited from the parents. And some studies have shown one-third of patients do not show mutation of the gene associated.  Cases have been observed in a variety of ethnicities from across the world, with no clear ethnic preference, suggesting that it can affect any demographic group.³ 

Understanding limb abnormalities in nager syndrome

Common limb and facial abnormalities 

Craniofacial abnormalities

Individuals with Nager syndrome frequently have distinct facial characteristics, which can have a variety of effects on their everyday lives. Here are some of the main craniofacial abnormalities:³

• Underdeveloped cheekbones (Malar Hypoplasia): This causes a sunken facial expression and might interfere with eating and speaking
• Eyes Slanting Downward (Down-slanting Palpebral Fissures) and no eyelashes: This feature may impair eye function or tear drainage in some circumstances
• Smaller or Shorter Lower Jaw (Micrognathia): A receding chin caused by a tiny lower jaw can cause feeding issues in infancy as well as tooth and bite misalignment as the kid develops. It also adds to respiratory problems, including obstructive sleep apnea during sleep
• Cleft Palate or Highly Arched Palate: A cleft palate is a split or opening in the roof of the mouth, whereas a highly arched palate has a large curvature. Both disorders make it difficult to eat and speak. A cleft palate may necessitate surgical intervention and increase the likelihood of ear infections
• Ear Abnormalities: Structural abnormalities in the ears can result in conductive hearing loss, which can impair speech and language development. Hearing aids or other therapies may be required to enhance hearing and communication skills. 60 percent of cases have hearing loss due to defects in the middle ear (conductive hearing loss)³ 

Limb abnormalities

Nager syndrome causes limb abnormalities, mostly in the upper extremities, but they can also affect the lower extremities. Here are some of the most frequent limb abnormalities:⁴

• Underdeveloped or absent Radius Bone in the Forearm (Radial Hypoplasia or Aplasia): This disorder can shorten the forearm and impair the ability to conduct daily activities that require forearm usage
• Thumb Anomalies (Absent or Hypoplastic Thumbs): Thumbs that are underdeveloped or missing can severely impede hand dexterity and functioning, limiting tasks like writing, buttoning garments, and handling items
• Shortened or missing forearm bones: This impairs upper-limb posture, resulting in functional problems
• Other Potential Limb Deformities, Including Lower Limb Abnormalities: Lower limb deformities can have an influence on mobility, balance, and walking ability. These may necessitate surgery, braces, or prostheses to enhance function and movement

Developmental implications

Children born with Nager syndrome suffer a variety of developmental problems that might affect their motor, cognitive, and verbal development. Understanding these consequences aids in providing the appropriate support and actions to foster their development and independence.

Motor development

Children with Nager syndrome frequently exhibit difficulties in motor development. Here are the specifics:

• Gross Motor Skills: Milestones as crawling, walking, and grabbing items may be delayed. This is due to limb anomalies, notably in the hands and arms, which impede their capacity to engage in these activities
• Writing, buttoning garments, and using utensils are all examples of fine motor skills that might be difficult to master. These activities rely largely on hand function, which is frequently affected in children with Nager syndrome

To address these delays:

• Adaptive Techniques and Tools: Various adaptive approaches and assistive gadgets can help children and adults accomplish daily tasks more independently. For example, specifically designed utensils and clothes with simple fastening may make a big impact

Cognitive and learning development

Children with Nager syndrome may experience difficulties with cognitive development, particularly in areas requiring problem-solving and adaptive methods. This can have numerous effects.

• School Participation: Some children may struggle with school activities, particularly those that entail hands-on work or demand fine motor skills. They may require adjustments and additional help to participate fully in the classroom
• Learning Support: Individualised educational strategies and the use of assistive technologies can help close the gap. This might involve using specialist software to help students study or hiring classroom assistants to give one-on-one assistance

Speech development

Nager syndrome-related craniofacial anomalies can have a major impact on speech development

• Speech Challenges: Cleft palates and narrow lower jaws might make it difficult to create particular sounds, resulting in delayed or impaired speech
• To overcome these difficulties, speech therapy is frequently required. Speech therapists can help children improve their articulation and communication abilities by employing exercises and approaches suited to their individual requirements

Orthopaedic management strategies

Orthopaedic care is critical for people with Nager syndrome since limb anomalies have a substantial influence on their functioning, mobility, and general quality of life, including independence. 

Early intervention and conservative management 

Children born with Nager syndrome are likely to need immediate medical care. First, the respiratory and feeding processes must be supported. Children with severe micrognathia may require both tube feeding and a tracheostomy tube to breathe. Infants may also have difficulty synchronising their breathing and feeding, needing a gastrostomy for feeding.

Oral and facial cleft reconstruction begins at 6 to 12 months of age, followed by eyelid deformity and cheekbone reconstruction at 2 to 3 years. Later in life, surgery on the nose and external ear may be performed (4 to 7 years old). 

Surgical interventions 

Indications for surgery 

Surgery is often utilised when conservative therapies, such as physiotherapy and occupational therapy, have failed to significantly improve functional ability or pain management. When substantial functional impairment arises, surgery should be performed as soon as possible. 

Types of surgical procedures 

Pollicization 

This is the process of creating a thumb from another finger, often the index finger.⁵ During the treatment, muscles, tendons, nerves, and blood arteries of the index finger are altered to allow it to act like a thumb while also shrinking and twisting to match thumb anatomy. This is used for those who have nonexistent or undeveloped thumbs. 

Radialization

This attempts to correct radial deviation (when the hand bends towards the thumb side owing to an undeveloped or nonexistent radius) while also enhancing hand alignment and usefulness.⁶ The hand is moved closer to the ulna (the long bone in the forearm). 

Tendon transfers 

Tendons are transferred from one region of the body (a healthy arm or leg) to another in order to restore muscular function and mobility when before there would have been considerable damage or dysfunction in the muscles or tendons controlling the hand or arm.⁷ This aims to develop fine motor abilities. 

Corrective osteotomies 

This method includes surgically cutting, relocating, and realigning the bone to address abnormalities.⁸ This helps to reduce discomfort caused by abnormal bone structure. 

Postoperative care and rehabilitation

Proper rehabilitation⁷ consists of wound care and antibiotics to avoid infection and promote healing, pain management following surgery, physical and occupational therapy, and education for patients and carers.  

Physical therapy 

The ultimate purpose of physical therapy is to improve the strength, range of motion, and function of the damaged limb(s). The main task of manual therapy in children with Nager syndrome is to increase mobility of the jaw joint. For patients with face/head deformities, heat treatments and relaxing are recommended as initial treatment, followed by treatments to increase range of motion. 

Resistance training and other strengthening exercises are used to build muscle strength and support weak or underdeveloped limbs. Resistance training involves using bands or weights to improve muscle growth and strength in the arms and legs. Isometric exercises, such as pressing your hands against a wall or squeezing a ball, can also assist in improving strength in the damaged limb(s) since the joint stays immobile while the muscles contract. This is especially beneficial for strengthening limbs with a restricted range of motion. 

Functional training aims to improve one's ability to do daily duties. This is supplied through task-specific training, such as practising reaching, grabbing, and lifting objects. Coordination exercises are also used to improve hand-eye coordination and fine motor skills, ultimately boosting movement precision.

Balancing activities such as standing on one leg or utilising balance boards can assist in improving balance. Proprioceptive activities, such as workouts on uneven surfaces, help to enhance joint position and body awareness. 

Stretching activities help to promote flexibility and avoid joint stiffness. Passive stretching involves a physiotherapist moving a patient's limbs through their range of motion. When someone actively stretches, they do the exercises themselves, following the suggested motions- including exercises of the tongue and mimic muscles, exercises for flexibility of the cervical spine, exercises for the muscles of the shoulder girdle and active breathing exercises. 

Occupational therapy 

This sort of therapy is designed to assist people in building abilities for everyday chores, including clothing, grooming, and personal hygiene. There may also be task-specific training, such as opening containers and manipulating tiny objects. Hand strengthening exercises are also utilised to improve grip and hand function, such as utilising putty, squeezing balls, or other specific equipment.  

Therapists examine the environments at work, school, and home and offer suggestions for enhancing accessibility. The use of assistive technology, such as programmable keyboards, specific writing instruments, and electronic support, can also be facilitated by therapists. 

Speech and hearing disorders require specialised logopedic treatment. 

Splinting and bracing 

The functional use of hands, wrists, and arms can be enhanced with the application of custom braces or splints. These help to preserve the correct alignment of the limbs and can avoid abnormalities resulting from imbalances in the muscles and development patterns linked to Nager syndrome. By uniformly transferring weight and supporting the joints, these devices can also aid in pain relief. 

Conclusion

Less than one person per million is affected by the rare genetic disorder known as Nager syndrome. It affects the growth of the bones and tissues in the face, arms, hands, and occasionally the legs and feet. It is present from birth. A tiny jaw, downward-sloping eyes, and underdeveloped cheekbones are some of the distinctive facial features of this condition. Limb abnormalities such as nonexistent or underdeveloped thumbs are also frequently present. 

In order to enhance functionality and quality of life, the syndrome's symptoms and complications can vary, necessitating comprehensive therapeutic options that may include physical and occupational therapy as well as occasionally surgical interventions. Important surgical techniques include tendon transfers, pollicization, radialization, and corrective osteotomies. These treatments are followed by intense postoperative care and rehabilitation. It is essential to recognise and manage the verbal, cognitive, and developmental difficulties linked to Nager syndrome to promote the independence and personal development of those who are impacted.