Nager syndrome is a rare condition that affects the face, hands, and arms. Most cases are caused by gene mutations, but some have unknown causes and most have no familial pattern. Clinical evaluations are used to diagnose the syndrome and approaches to treatment can include surgery and physical therapy.
Definition & Facts
Nager syndrome is exceptionally rare and its causes are unknown. 75 cases of it have been documented. Though it is usually not inherited and occurs in those without a family history of the condition, some cases may be inherited in an autosomal dominant inheritance pattern or an autosomal recessive inheritance pattern.
Symptoms & Complaints
Small children can have a small lower jaw (micrognathia) that causes breathing problems and underdeveloped cheekbones (malar hypoplasia). They will often have a cleft palate that makes feeding difficult.
Other features can include eyes slanted downwards, absent eyelashes, eyelid coloboma, and small ears that contribute to hearing loss among 60 percent of these individuals and affect speech. Bone abnormalities are also present in the hands, arms, feet, and legs.
The absence or malformation of thumbs is the most commonly seen symptom. Fingers may be curved (clinodactyly) or fused together (syndactyly), and forearms are short due to a malformed radius. Less common abnormalities can occur in the heart, kidneys, genitalia, and urinary tract.
The main cause of Nager syndrome when it is autosomal dominant is the existence of gene mutations of the SF3B4 gene. A gene mutation results in the faulty, absent, or inefficient function of proteins. Scientist know the SF3B4 gene is located on the long arm of chromosome 1.
Humans usually have 46 chromosomes, with pairs numbered 1 - 22 and a sex chromosome. Each chromosome has a short arm (p) and long arm (q), and it’s further subdivided into numbered bands. Genetic diseases are determined by the combination of genes received from the mother and father. A dominant genetic disorder only needs a single copy of a gene, and it can be inherited from either parent or a completely new mutation.
Individuals with Nager syndrome have a change in one copy of the SF3B4 gene. It is usually a sporadic condition, meaning mutations occur at the sperm/egg formation for the child only with no family inheritance.
Diagnosis & Tests
Various tests are used to diagnose Nager syndrome including a facial dysostosis sequencing panel and a SF3B4 gene sequence analysis. A good portion of these diagnostic test involve molecular genetic testing that detects mutations in the SF3B4 gene. These diagnostic services are offered at specialized laboratories.
Clinical evaluations and detailed medical history, along with basic physical examinations can confirm the presence of this syndrome since a good portion of symptoms associated with the syndrome are physical. Most physical abnormalities are present at birth (congenital).
There are also specialized X-ray studies that can confirm the presence and extent of craniofacial abnormalities. For example, they may reveal micrognathia due to the development of mandibular hypoplasia and malar hypoplasia which are indicative of Nager syndrome.
Treatment & Therapy
Treatment for Nager syndrome usually involves some form of surgery. Surgery to insert breathing and/or feeding tubes in infants so that they can breath and eat due to palate abnormalities such as cleft palate may be necessary. Surgery for the ears may also be needed depending on the severity of the impairment. Multiple surgeries may be necessary to correct eye and jaw abnormalities. Rib and elbow abnormalities that cause movement of the arms to be difficult, along with scoliosis may need surgery also.
Physical therapy can be used to improve hand and feet use. Speech therapy can be helpful to those with hearing and language development issues. Treatment will always be directed towards specific symptoms, meaning that coordinated efforts from a team of specialists may be required.
Prevention & Prophylaxis