Apert syndrome – Symptoms, Causes, and Diagnosis.

Description

Apert syndrome, also known as “acrocephalosyndactyly”. It is a genetic disorder in which certain skull bones fuse together prematurely, which is known as craniosynostosis. This early fusion of the skull prevents it from developing normally and causes the child to have an unusual head and face shape. Children with this condition may also have cognitive (thinking) impairments, webbed or fused fingers, and toes, or extra digits.

Pathophysiology

FGFR2 is widely expressed in cartilage, osteoprogenitor cells, limb mesenchyme, skin, and the brain. The receptor is composed of three extracellular immunoglobulin-like domains, a transmembrane portion, and an intracellular tyrosine kinase which work together to transmit signals from the extracellular environment to downstream intracellular pathways. Two missense mutations, Serine252Trp and Pro253Arg, are responsible for almost all cases of AS and lead to alterations in the linker region between immunoglobulin-like loop II and loop III of FGFR2.

Premature coronal suture closure in the prenatal and early infancy periods leads to restricted growth perpendicular to the suture, resulting in brachycephaly (decreased anterior-posterior dimension). There is generally an associated midline defect from the glabellar to the posterior fontanelle which allows for brain growth and cranial expansion laterally. The altered positioning of the sphenoid bone and midface leads to decreased orbital volume and its related manifestations: ocular hypertelorism, proptosis, and down-slanting palpebral fissures. Maxillary hypoplasia causes severe narrowing of the nasopharyngeal and oropharyngeal space which may lead to severe sleep apnea.

Causes

Apert syndrome is a genetic condition caused by a mutation in a specific gene.

  • Apert syndrome is a birth abnormality caused by a mutation of the FGFR2 gene. This can occur in babies with no family history of the disorder, or they can inherit it from a parent.
  • The FGFR2 gene produces a protein called fibroblast growth factor receptor 2. This protein has many important roles in a fetus’ development, including a key role in signaling bone cell development.
  • When this gene mutation occurs, FGFR2 continues to signal for longer than usual, leading to early fusion of the skull, facial, feet, and hand bones.

Mutations in the FGFR2 gene can also cause several other related disorders, including:

  • Pfeiffer syndrome
  • Crouzon syndrome
  • Jackson-Weiss syndrome

Risk factors

  • Increased paternal age has been noted to be a risk factor for Apert syndrome. Males and females are equally affected.
  • Most cases of AS are due to sporadic mutations which exhibit a paternal age effect, hence advanced paternal age confers an increased risk of having a child with AS.
  • If the parents are unaffected but have a child with AS, the risk to future is offspring is minimal.
  • AS is inherited in an autosomal dominant fashion, so if either parent has the disease, their offspring have a 50% risk of inheriting the mutation.

Symptoms

  • Craniosynostosis: early closure of growth plates of the skull, resulting in a change in the shape of the head and possible increased pressure on the brain
  • Midfacial hypoplasia: the decreased growth of the central face, causing sunken facial appearance and potentially dangerous breathing problems or sleep apnea
  • Syndactyly: fusion of the fingers and/or toes
  • Other features may include: crowded teeth, cleft palate, hearing loss, fused spinal bones, and severe acne

Complications

  • Hand deformities can be quite severe and prevent your child from functioning normally.
  • Apert Syndrome can be associated with hydrocephalus, sleep apnea, eye exposure issues when the eyelids can’t close completely and airway compromise that may require the tracheostomy.
  • Patients with Apert syndrome may have associated intellectual or developmental disabilities.
  • Specific cognitive deficits that may impact children with craniosynostosis include impairments in domains such as visuospatial functioning, executive functioning, attention, memory, or general developmental delay.
  • Frequent ear infections: People with Apert syndrome have an increased risk of experiencing frequent ear infections.

Diagnosis and Test

Apert syndrome can be diagnosed based on the presence of the following features:

  • Turribrachycephalic skull shape (cone-shaped or towering skull) which is visibly apparent and can be confirmed by skull radiograph or head CT examination

  • Characteristic facial features including moderate-to-severe underdevelopment of the midface, bulging and wide-set eyes, “beaked” nose, underdeveloped jaw and shallow eye sockets
  • Variable hand and foot findings such as syndactyly of the fingers and toes and polydactyly

Molecular genetic testing can help to confirm the diagnosis.

Treatment and Medications

Most children with Apert syndrome will require numerous operations in their adolescence and early adulthood. Your child may need surgeries to:

  • Reshape the skull
  • Improve the upper airway, which may be partly blocked
  • Correct eye problems
  • Address dental problems
  • Separate webbed fingers or toes

Our doctors have significant expertise in:

  • Minimally invasive techniques and helmet therapy to reduce your child’s skull shape deformity
  • Midfacial advancement (also known as Le Fort III procedures) to bring the middle part of your child’s face forward, opening up the airway and protecting the prominent eyes
  • Treating airway obstruction
  • Jaw surgery, combined with orthodontic therapy, to help correct the bite and improve jaw appearance and function
  • Complex operations to separate and straighten fingers and toes

Endoscopic craniosynostosis repair. This minimally invasive procedure uses a small scope and leaves only small scars. After endoscopic craniosynostosis repair, your child will need to wear a helmet for several months. We will help you make all the arrangements for this. Learn more about post-surgical helmets.

Open craniosynostosis repair surgery. This classic surgical approach can be performed on children of any age. It involves a larger incision plus the use of plates to hold the bones in place. Our surgeons have performed thousands of open craniosynostosis repairs over more than 35 years.

Prevention

  • There is currently no known method of prevention against Apert syndrome.
  • Individuals who have Apert syndrome may meet with genetic counselors to learn more about the risks of having children with the disorder. If one parent has Apert syndrome, there is a 50% chance with each birth that a child will inherit the condition. However, nearly all cases of Apert syndrome occur randomly and are not inherited.
  • Prenatal screening and diagnostic tests may also be performed to determine if a mother’s fetus has Apert syndrome. However, there are serious risks associated with prenatal testing, including miscarriage. Therefore, patients should discuss the potential health risks and benefits before making any health-related decisions.

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3 comments

  1. As it’s genetically inherited, After how many year(s) is it inherited?? ((as the parents(mother) gives birth immediately or later in dynasty)).!!

  2. I love this app and this helps on updating about new disease but when I see treatment why physiotherapy treatment is not included . I see so many disease which after physiotherapy can atleast obtain functional recovery at minimal cost.

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