User:Kelsh9610/Acrocephalosyndactyly

Syndactyly in acrocephalosyndactyly (Apert)

Acrocephalosyndactyly (from Greek ἄκρος (ákros) ‘highest, at the extremity’, κεφαλή (kephalḗ) ‘brain or head’, σύν (syn) 'together' and δάκτυλος (daktylos) 'finger') is a group of congenital disorders characterized by abnormalities of the face and skull (craniosynostosis), and hands and feet (syndactyly). When polydactyly is also present, the classification is acrocephalopolysyndactyly. Acrocephalosyndactyly is usually diagnosed after birth, although prenatal diagnosis is sometimes possible if the mutation is present in family members, as the disorders are usually inherited in an autosomal dominant pattern. Treatment often involves surgery in early childhood to correct for craniosynostosis and syndactyly.The severity of symptoms for acrocephalosyndactyly varies significantly by subtype and treatment in the early stages of life.

History

Cases of the disorder have been recorded as early as the 18th century. In 1906, French physician Eugène Apert first described the disorder characterized by acrocephaly and syndactyly to which the term acrocephalosyndactyly was first applied. The disorder described by Apert is now known as the Apert syndrome subtype of acrocephalosyndactyly. Other subtypes of acrocephalosyndactyly were characterized throughout the 20th century.

Prevalence

Considering all types of acrocephalosyndactyly, one newborn baby is born with acrocephalosyndactyly for every 65,000 - 102,500 babies born. There is no difference in the amount of males and females affected by acrocephalosyndactyly.

Characteristics

Acrocephalosyndactyly presents in numerous different subtypes, however, considerable overlap in symptoms occurs. Generally, all forms of acrocephalosyndactyly are characterized by atypical craniofacial, hand, and foot characteristics, such as premature closure of the fibrous joints in between certain bones of the skull, fusion of certain fingers or toes, and/or more than the usual number of digits. Some subtypes also involve structural heart variations that are present at birth.

Cause

Most forms of acrocephalosyndactyly or acrocephalopolysyndactyly are inherited in autosomal dominant pattern, with the exception of Carpenter Syndrome which is inherited in autosomal recessive manner. De-novo variants, or genetic alterations not inherited from one’s parents in different genes were reported to cause several types of acrocephalosyndactyly. Among known genetic changes, there are mutations in genes such as Fibroblast growth factor receptor (FGFR), TWIST1, and RAB23. Constitutive activation in these categories of genes, particularly FGFR, which is heavily involved during the development stage of embryos such as organ development or organogenesis and the maintenance of tissue forming cells, known as progenitor cells, can be very detrimental.

Genetically inherited acrocephalosyndactyly conditions all show high to complete penetrance with a variable expression, meaning that all individuals who inherit the condition present atypical characteristic craniofacial, hand, and foot strucutures, but the severity of disabilities is variable. Increased paternal age is considered a risk factor in some cases.

Impact of Condition on Life

Despite the current major efforts of surgical therapeutics on the effects of Acrocephalosyndactyly, morbidities still exist within individuals that have received treatment. Those who reach adulthood often have lower levels of education than their peers, as well as greater difficulty in various social aspects, such as dating, marriage, or sexual relationships. They may also report the need for assisted living throughout their life as well as other health issues, such as hearing issues or epilepsy at a more common frequency than their counterparts.

Fortunately, many individual with the condition report similar levels of happiness with their lives as non-afflicted individuals and show high social integration as well as great physical and emotional resilience despite any impediments.

Nomenclature and Classification

There is no consistent nomenclature or classification across the different syndromes under the umbrella of acrocephalosyndactyly and acrocephalopolysyndactyly. Although acrocephalosyndactyly has been reported as early as the 18th century, the ACS and ACPS classifications only came in the latter 20th century. However, this classification may be outdated as it has been suggested that the distinction between acrocephalosyndactyly and acrocephalopolysyndactyly should be erased.

Currently, Noack syndrome (ACPS type I) is now classified as Pfeiffer syndrome (ACS type V); Goodman syndrome (ACPS type IV) is classified as a variation of Carpenter syndrome(ACPS type II); and different researchers have combined Apert (ASC type I), Crouzon(ASC type II), and Pfeiffer (ASC type V) syndrome into Apert-Crouzon and Crouzon-Pfeiffer syndrome.

Acrocephalosyndactyly type IV was formerly called Mohr Syndrome, however, it was later classified under Orofaciodigital syndrome type II. Pfeiffer syndrome was formerly type VI and Waardenburg type V, but this was changed sometime after 1966.  

Patient with Apert (ACS Type I) syndrome

Acrocephalosyndactyly (ACS):

• type I – Apert syndrome
• type II – Crouzon syndrome
• type III – Saethre–Chotzen syndrome
  • Robinow-Sorauf syndrome suggested to be included in Saethre-Chotzen classification
• type IV – Mohr syndrome (archaic)
• type V – Pfeiffer syndrome
  • Noack syndrome incorporated into Pfeiffer syndrome classification

A related term, acrocephalopolysyndactyly (ACPS), refers to the inclusion of polydactyly to the presentation. It also has multiple types:

Patient with Crouzon (ACS Type II) syndrome

• type I – Noack syndrome (archaic)
• type II – Carpenter syndrome
  • Goodman syndrome incorporated into Carpenter syndrome classification
  • Summitt syndrome incorporated into Carpenter syndrome classification
• type III – Sakati-Nyhan-Tisdale syndrome

type IV –  Goodman syndrome (archaic)

Treatment

Craniosynostosis

For subtypes with craniosynostosis, surgery is required to prevent premature fusion of cranial sutures, such as the coronal suture (brachycephaly). Cranioplasty should be performed in the first year of life to prevent disruptions in brain growth due to increased intracranial pressure. Midface surgery may also be required in childhood to detach the midface from the rest of the skull to correct respiratory and orthodontic problems.

Syndactyly

Syndactyly in certain subtypes is rarely severe enough to affect hand function, so treatment may not be needed.

In more severe subtypes, as seen in Apert syndrome, surgical correction of syndactyly may be needed. Surgery is recommended to be performed as soon as possible, generally at 4 months of age. Treatment is dependent on the severity of syndactyly. The surgical treatment generally involves interdigital webspace release and thumb lengthening.

Management

Treatment for those diagnosed with acrocephalosyndactyly extends beyond surgery. There are many steps that can aid in long-term management of the syndrome. Individuals afflicted with acrocephalosyndactyly and their caregivers can build a health care support system by building strong relationships with a team of medical specialists. Preformed teams of medical specialists can often be found at universities or research institutions. Caregivers can prevent future challenges by exploring options for financial aid, health insurance, and accommodating educational institutions. Primary caregivers are encouraged to prioritize their emotional health by reserving time for themselves and by sourcing a reliable support system.