Is There a Cure for Nager Syndrome?

Also known as acrofacial dysostosis (AFD), Nager syndrome is a rare genetic congenital malformation syndrome characterized by mandibulofacial dysostosis (malar hypoplasia, micrognathia, external ear malformations) and variable preaxial limb defects.

A child with Nager syndrome is born with normal intelligence but underdeveloped bones in their face, hands, and arms.

Other names for Nager syndrome include:

• Acrofacial dysostosis I, Nager type
• NAFD
• AFD1
• Nager acrofacial dysostosis
• Preaxial acrofacial dysostosis
• Preaxial mandibulofacial dysostosis
• Nager acrofacial dysostosis syndrome

In more than 50 percent of patients, Nager syndrome is caused by genetic heterozygous mutations or changes in the SF3B4 gene with autosomal dominant inheritance (one copy of the altered gene is sufficient to cause the disorder).

Researchers also speculate that autosomal recessive inheritance (both copies of a gene in each cell have mutations) is suspected based on sibling recurrence in consanguineous families.

The severity of symptoms varies among affected children.

The characteristics and symptoms of Nager syndrome may include:

• Mandibulofacial anomalies
  • Downward slant of palpebral fissures and eyes
  • Coloboma (notching at the corners of eyes)
  • Ptosis of upper lids
  • Coloboma of lower lids
  • Deficiency or absence of eyelashes in the medial one-third to two-thirds of the lower eyelids
  • Hypoplasia of the malar eminences
  • Hypoplasia of the maxilla
  • Cleft palate 
  • Absence or hypoplasia of the palatal velum
  • Choanal atresia (narrowed or blocked nasal cavity)
  • Malar hypoplasia (underdeveloped cheekbones) 
  • Micrognathia (small jaws)
  • Microtia (small, low-set, cupped, missing, deformed, or malformed outer ears)
  • Extension of the tongue of temporal hair down the sides of the cheeks
  • Cleft lip
• Limb defects
  • Leg, foot, and toe malformations
  • Underdeveloped, malformed, or absence of thumbs
  • Radio-ulnar synostosis (abnormal connection of the radius and the ulna) and/or aplasia/hypoplasia of the radius
  • Triphalangeal thumbs (presence of an extra copy of phalange)
  • Clinodactyly (unusually curved fingers) or syndactyly (fused fingers)
  • Phocomelia (severely shortened upper limbs)
  • Webbing of the toes
  • Clubfeet
  • Hallux valgus (abnormal inward turning of the big toe toward the index finger)
• Otologic and oral anomalies
  • Eating and speech difficulties
  • Middle ear malformations
  • Conductive hearing loss
  • Upper respiratory airway obstruction
• In rare cases, issues with the heart, kidney, genitalia, and urinary tract

Nager syndrome is diagnosed through the following:

• Physical examination: To look for physical characteristics of the condition
• Radiological examination: To examine the bones of the face, hands, and arms
• Genetic testing: To examine the sample for any changes in the DNA, chromosomes, or proteins