Nager acrofacial dysostosis (NAFD) is a rare genetic disorder that affects the development of facial bones and limbs. It is also known as Nager syndrome or Nager syndrome type 1. This condition is characterized by distinctive facial features, such as a cleft palate, underdeveloped cheekbones, abnormally shaped ears, and limb anomalies, including shortened forearms and thumbs, and absent or malformed thumbs.
NAFD is caused by mutations in the SF3B4 gene, which is located on chromosome 1. This gene provides instructions for making a protein that is involved in the splicing of messenger RNA (mRNA). mRNA is a molecule that carries genetic information from DNA to the ribosome, where it is translated into proteins. Mutations in the SF3B4 gene disrupt the normal splicing process, leading to the production of abnormal proteins that interfere with normal development.
NAFD is inherited in an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutated gene from one parent to develop the condition. In some cases, however, NAFD may be caused by a new mutation in the SF3B4 gene, which means that the affected individual is the first person in their family to have the condition.
Causes
Causes of Nager acrofacial dysostosis, along with detailed explanations of each cause.
- Genetic mutations: Nager acrofacial dysostosis is caused by mutations in the SF3B4 or SF3B4 genes. These mutations can be inherited from one or both parents, or they can occur spontaneously.
- Autosomal dominant inheritance: In some cases, Nager acrofacial dysostosis is inherited in an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutated gene from a parent to develop the disorder.
- Sporadic mutations: In other cases, Nager acrofacial dysostosis occurs due to spontaneous mutations that happen for no apparent reason.
- De novo mutations: De novo mutations are mutations that occur for the first time in a family. They are not inherited from either parent, but instead occur randomly during the development of the egg, sperm, or embryo.
- Advanced paternal age: Studies have shown that advanced paternal age may increase the risk of de novo mutations, which could contribute to the development of Nager acrofacial dysostosis.
- Prenatal exposure to toxins: Exposure to certain toxins during pregnancy, such as alcohol or drugs, may increase the risk of developing Nager acrofacial dysostosis.
- Intrauterine growth restriction: In some cases, Nager acrofacial dysostosis may be caused by intrauterine growth restriction, which means that the fetus does not grow properly in the womb.
- Craniofacial abnormalities: The abnormal development of the craniofacial region, which includes the skull, face, and neck, may contribute to the development of Nager acrofacial dysostosis.
- Abnormal bone development: Nager acrofacial dysostosis is primarily characterized by abnormal bone development, which may affect the facial bones, hands, and arms.
- Absence of thumbs: One of the most common physical features of Nager acrofacial dysostosis is the absence of thumbs or the presence of small, underdeveloped thumbs.
- Short stature: Many individuals with Nager acrofacial dysostosis have a shorter-than-average stature.
- Malformations of the ears: Malformations of the ears, including absence or malformation of the outer and middle ear, are common in individuals with Nager acrofacial dysostosis.
- Hearing loss: Hearing loss is a common complication of Nager acrofacial dysostosis, and may be caused by malformations of the ear or other factors.
- Cleft palate: A cleft palate is a condition in which the roof of the mouth does not fuse properly during development, leading to an opening in the roof of the mouth. It is a common feature of Nager acrofacial dysostosis.
- Feeding difficulties: Feeding difficulties are common in infants with Nager acrofacial dysostosis, and may be caused by the presence of a cleft palate or other factors.
- Breathing difficulties: Breathing difficulties may occur in individuals with Nager acrofacial dysostosis due to abnormalities in the development of the upper airway.
- Dental abnormalities: Dental abnormalities, including missing or malformed teeth, are common
Symptoms
The symptoms of Nager acrofacial dysostosis can vary greatly from person to person, and not all people with the condition will have every symptom. However, there are several characteristic features that are often seen in individuals with Nager syndrome.
- Abnormal facial features: The most prominent symptom of Nager syndrome is abnormal facial features. These may include a small or absent jawbone (mandible), droopy eyelids (ptosis), down slanting palpebral fissures (the opening between the eyelids), and a flat midface. Some individuals may also have a cleft palate or lip.
- Abnormalities of the ears: People with Nager syndrome often have malformed ears, which may be small, low-set, or absent altogether. There may also be hearing loss, which can be conductive or sensorineural.
- Limb abnormalities: Nager syndrome can cause a wide range of limb abnormalities, including underdeveloped or absent thumbs, shortened forearms, and absent or fused wrist bones. The fingers may also be short and curved, and the nails may be abnormal or absent.
- Hand and foot abnormalities: In addition to the thumb abnormalities mentioned above, people with Nager syndrome may have other hand and foot abnormalities, such as small or absent fingers and toes, abnormal curvature of the fingers or toes, or webbing between the fingers or toes.
- Abnormalities of the skeletal system: Nager syndrome can cause abnormalities of the skeletal system, including a curved spine (scoliosis), abnormal curvature of the legs (tibial bowing), and abnormal curvature of the arms (ulnar deviation).
- Respiratory problems: Individuals with Nager syndrome may have respiratory problems due to the small jaw and airway abnormalities. This can cause sleep apnea, which can lead to daytime sleepiness, fatigue, and other complications.
- Dental abnormalities: People with Nager syndrome often have dental abnormalities, such as missing or malformed teeth, delayed eruption of teeth, and misaligned teeth.
- Gastrointestinal abnormalities: Nager syndrome can cause gastrointestinal abnormalities, such as reflux, constipation, and feeding difficulties.
- Cardiovascular abnormalities: Some individuals with Nager syndrome may have cardiovascular abnormalities, such as an atrial septal defect (a hole in the wall between the two upper chambers of the heart) or patent ductus arteriosus (a blood vessel that should close after birth but remains open).
- Genitourinary abnormalities: Nager syndrome can cause genitourinary abnormalities, such as absent or malformed kidneys, abnormal ureters, and genital abnormalities.
- Growth delays: People with Nager syndrome may experience growth delays, particularly in the limbs.
- Developmental delays: Some individuals with Nager syndrome may experience developmental delays, particularly in speech and language development.
- Cognitive impairment: In some cases, Nager syndrome may be associated with cognitive impairment, although this is not always the case.
- Eye abnormalities: In addition to the droopy eyelids and down-slanting palpebral fissures mentioned above, people with Nager syndrome may have other eye abnormalities, such as strabismus (crossed eyes) or nystagmus (involuntary eye movements).
- Skin abnormalities: Nager syndrome can cause skin abnormalities, such as dry skin, hyperpigmentation (darkening of the skin), or patches of thickened skin.
Diagnosis
Diagnosis and tests for Nager acrofacial dysostosis.
- Physical Examination: A thorough physical examination is the first step in diagnosing Nager acrofacial dysostosis. A physical exam can reveal craniofacial abnormalities, such as downward-slanting eyes, underdeveloped cheekbones, and micrognathia (a small lower jaw). Limb abnormalities, such as underdeveloped or absent thumbs, may also be noted.
- Family History: Nager acrofacial dysostosis is an inherited disorder, so a family history of the condition may suggest a diagnosis.
- Genetic Testing: Genetic testing can confirm a diagnosis of Nager acrofacial dysostosis. DNA sequencing can identify mutations in the SF3B4 gene, which causes the disorder.
- X-Ray: X-rays of the skull and limbs can show abnormalities in bone development.
- CT Scan: A CT scan of the head can show the shape and size of the skull and facial bones, and identify any abnormalities in the development of the ear canal.
- MRI: An MRI can provide detailed images of the brain, inner ear, and surrounding structures, and identify any abnormalities in their development.
- Audiometry: A hearing test can evaluate hearing loss, which is a common feature of Nager acrofacial dysostosis.
- Ophthalmologic Exam: An ophthalmologic exam can evaluate vision and identify any abnormalities in the development of the eye.
- Cardiac Evaluation: A cardiac evaluation can assess the function of the heart and identify any abnormalities in its development.
- Pulmonary Evaluation: A pulmonary evaluation can assess lung function and identify any abnormalities in lung development.
- Renal Evaluation: A renal evaluation can assess kidney function and identify any abnormalities in their development.
- Gastrointestinal Evaluation: A gastrointestinal evaluation can assess digestive function and identify any abnormalities in the development of the digestive system.
- Neurological Evaluation: A neurological evaluation can assess brain function and identify any abnormalities in the development of the brain.
- Developmental Assessment: A developmental assessment can evaluate cognitive, motor, and language development.
- Feeding Assessment: A feeding assessment can evaluate feeding difficulties, which are common in infants with Nager acrofacial dysostosis.
- Speech Assessment: A speech assessment can evaluate speech development and identify any abnormalities in speech production.
- Orthopedic Evaluation: An orthopedic evaluation can assess limb function and identify any abnormalities in the development of the limbs.
Treatment
Treatments for Nager acrofacial dysostosis and explain the details of each treatment.
- Surgery: Surgery may be necessary to correct abnormalities of the face, hands, and arms. The type of surgery required will depend on the specific abnormalities present and may include procedures to correct the jaw, palate, and eyes.
- Speech therapy: Many individuals with Nager acrofacial dysostosis have difficulty with speech due to a cleft palate or other abnormalities of the mouth. Speech therapy can help improve speech and communication skills.
- Occupational therapy: Occupational therapy can help individuals with Nager acrofacial dysostosis develop fine motor skills and learn how to perform daily tasks such as dressing, eating, and writing.
- Physical therapy: Physical therapy can help improve strength and mobility in the arms and hands, which may be affected by abnormalities associated with Nager acrofacial dysostosis.
- Nutritional support: Individuals with Nager acrofacial dysostosis may have difficulty eating due to abnormalities of the jaw and palate. Nutritional support, such as feeding tubes or special diets, may be necessary to ensure proper nutrition.
- Hearing aids: Some individuals with Nager acrofacial dysostosis may experience hearing loss. Hearing aids can help improve hearing and communication abilities.
- Assistive technology: Assistive technology such as communication devices or adaptive equipment may be helpful in improving communication and daily functioning for individuals with Nager acrofacial dysostosis.
- Antibiotics: Antibiotics may be prescribed to treat ear infections or other infections that are common in individuals with Nager acrofacial dysostosis.
- Pain management: Pain management techniques such as medication or physical therapy may be helpful in managing pain associated with Nager acrofacial dysostosis.
- Orthodontic treatment: Orthodontic treatment may be necessary to correct dental abnormalities associated with Nager acrofacial dysostosis.
- Maxillofacial prosthetics: Maxillofacial prosthetics such as artificial jaws or teeth may be necessary to improve eating, speaking, and overall facial appearance.
- Psychological support: Psychological support such as counseling or therapy may be beneficial for individuals with Nager acrofacial dysostosis and their families to help cope with the emotional challenges associated with this condition.
- Genetic counseling: Genetic counseling can help individuals with Nager acrofacial dysostosis and their families understand the inheritance pattern and risks associated with this condition.
- Pain management: Pain management techniques such as medication or physical therapy may be helpful in managing pain associated with Nager acrofacial dysostosis.
- Dental care: Regular dental checkups and cleanings are important for individuals with Nager acrofacial dysostosis to maintain healthy teeth and gums.
- Eye exams: Regular eye exams are important for individuals with Nager acrofacial dysostosis to monitor for any vision problems.
- Ophthalmic treatment: Ophthalmic treatments such as glasses, contact lenses, or surgery may be necessary to correct vision problems associated with Nager acrofacial dysostosis.
References
Previous
Mulberry Molars
Next
