Nager acrofacial dysostosis, also known as Nager syndrome, is a genetic disorder which displays several or all of the following characteristics:
underdevelopment of the cheek and jaw area, down-sloping of the opening of the
eye
Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...
s, lack or absence of the lower
eyelashes, kidney or stomach
reflux,
hammer toes, shortened
soft palate
The soft palate (also known as the velum, palatal velum, or muscular palate) is, in mammals, the soft tissue constituting the back of the roof of the mouth. The soft palate is part of the palate of the mouth; the other part is the hard palate. ...
, lack of development of the
internal and external
ear, possible
cleft palate, underdevelopment or absence of the
thumb
The thumb is the first digit of the hand, next to the index finger. When a person is standing in the medical anatomical position (where the palm is facing to the front), the thumb is the outermost digit. The Medical Latin English noun for thumb ...
,
hearing loss
Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...
(see
hearing loss with craniofacial syndromes) and shortened
forearm
The forearm is the region of the upper limb between the elbow and the wrist. The term forearm is used in anatomy to distinguish it from the arm, a word which is most often used to describe the entire appendage of the upper limb, but which in anat ...
s, as well as poor movement in the
elbow, and may be characterized by accessory
tragi
The tragus is a small pointed eminence of the external ear, situated in front of the concha, and projecting backward over the meatus. It also is the name of hair growing at the entrance of the ear. Its name comes the Ancient Greek (), meaning 'g ...
.
Occasionally, affected individuals develop vertebral anomalies such as
scoliosis
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
.
The inheritance pattern is
autosomal, but there are arguments as to whether it is
autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
or
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
. Most cases tend to be sporadic. Nager syndrome shares many characteristics with five other craniofacial syndromes:
Miller,
Treacher Collins,
Pierre Robin,
Genee–Wiedemann and
Franceschetti–Zwahlen–Klein.
Genetics
While Nager syndrome is thought to be most often caused by
haploinsufficiency
Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...
of the
spliceosomal
A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to speci ...
factor
SF3B4
Splicing factor 3B subunit 4 is a protein that in humans is encoded by the ''SF3B4'' gene.
Function
This gene encodes one of four subunits of the splicing factor 3B. The protein encoded by this gene cross-links to a region in the pre-mRNA imme ...
,
in over one third of patients tested, the SF3B4 mutation is not found.
Genetic sequencing shows that the syndrome can be caused by either autosomal recessive or autosomal dominant inheritance.
Treatment
Due to craniofacial development, it is recommended that families work closely with craniofacial specialists as soon as Nager is recognized or suspected. Children born with Nager may need intubation immediately after birth, requiring tube feeding and a tracheotomy tube to help with breathing. Surgical intervention is commonly necessary to increase mandibular mobility. As the child grows and develops, further surgery is usually required on the lower jaw and is often done in tandem with orthodontic treatments.
Further treatment depends upon the symptoms of the individual patient and may include oral surgery, plastic surgery, audiological intervention to manage hearing loss, speech therapy, and surgery on the limbs to aid with mobility limitations.
See also
*
Dermoid cyst
References
External links
Cutaneous congenital anomalies
Congenital disorders
Rare syndromes
Syndromes with dysmelia
Syndromes with cleft lip and/or palate
Syndromes affecting hearing
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