Acrocephalopolysyndcatyly - Types, Causes, Symptoms, and Management

Introduction

Acrocephalosyndactyly is a rare genetic disorder that affects the development of bones and other tissues in the body. There are different types of acrocephalopolysyndactyly. Acrocephalopolysyndactyly (ACPS) is closely related to another syndrome called acrocephalosyndactyly (ACS) syndromes.

What Is Acrocephalopolysyndactyly?

Acrocephalopolysyndactyly is an uncommon genetic disorder marked by premature fusion of skull bones, atypical head and facial shape, and abnormalities in the hands and feet, including additional digits.

What Are the Types and Causes of Acrocephalopolysyndactyly?

Acrocephalopolysyndactyly is classified into the following types.

• Type I - Noack Syndrome.

  • It is a Pfeiffer syndrome variant characterized by craniosynostosis, hand and foot malformations, and midfacial hypoplasia.

  • A Noack syndrome is caused due to mutations in the FGFR2 gene and rarely the FGFR1 gene.

  • The inheritance pattern of Noack syndrome is autosomal dominant.

• Type II - Carpenter Syndrome.

  • It is the most common type of acrocephalosyndactyly.

  • It is characterized by a variety of symptoms affecting different body systems. Common features include craniosynostosis, abnormalities of fingers and toes, and intellectual disability.

  • Carpenter syndrome is caused mainly due to mutations in the RAB23 gene and rarely by the mutation in the MEGEF8 gene.

  • The mode of inheritance is autosomal recessive.

• Type III - Sakati-Nyhan Syndrome.

  • It is an extremely rare type of acrocephalopolysyndactyly.

  • The common symptoms of Sakati-Nyhan syndrome include craniofacial defects, congenital heart defects, and limb abnormalities.

  • The same gene causing this syndrome is unknown. It is believed that the mode of inheritance for this condition is autosomal dominant.

• Type IV - Goodman Syndrome.

  • This is also a short form of acrocephalopolysyndactyly.

  • It is considered a variant of Carpenter syndrome and is of autosomal recessive inheritance.

  • It has all the symptoms common to acrocephalopolysyndactyly.

What Are the Signs and Symptoms Associated With Acrocephalopolysyndactyly?

Acrocephalopolysyndactyly syndromes have a wide range of symptoms that affect various body systems. Symptoms in each affected individual vary according to the severity of the condition. The combination of signs and symptoms also varies between the different types of syndromes in the acrocephalopolysyndactyly group of syndromes. Some of the symptoms associated with acrocephalosyndactyly are listed below.

• Symptoms Related to Fingers and Toes.

  • Brachydactyly - Digits (fingers and toes) that are shorter than average.

  • Syndactyly - The complete or partial fusion of one or more fingers and toes.

  • Polydactyly - The presence of one or more extra fingers.

  • Broad thumb.

  • Clinodactyly - The presence of a hook-like bend on one or more fingers.

  • Camptodactyly - Bent middle joint in the fingers that cannot be straightened out.

• Craniofacial Symptoms

  • Abnormal skull morphology.

  • Craniosynostosis - An early fusion of two or more bones of the skull.

  • Oxycephaly or Acrocephaly - The top of the skull is cone-shaped.

  • The cloverleaf skull is a skull abnormality due to the early closure of the sutures in the head.

  • Turricephaly - The head appears tall with reduced length and width due to the premature closure of the corona suture.

  • Flat nasal bridge.

  • Abnormally shaped and low-set ears.

  • Underdeveloped upper and lower jaws.

  • Narrow and high-arched palate.

  • Abnormally shaped eyes.

  • Abnormal cornea morphology.

  • Dental problems.

  • Vision problems.

• Other Symptoms

  • Intellectual disability.

  • Obesity.

  • Congenital heart defects include atrial septal, ventricular septal, tetralogy of Fallot, patent ductus arteriosus, pulmonary stenosis, etc.

  • Cryptorchidism or undescended testes.

  • Abnormal reproductive system morphology.

  • Genu Valgum - Knees bent inward and appear closer together.

  • Umbilical hernia.

  • Kyphoscoliosis.

  • Polysplenia - Multiple small spleens instead of a fully functioning normal-sized spleen.

  • Talipes equinovarus or clubfoot.

  • Breathing difficulties due to the abnormal development of the skull and face.

How Is Acrocephalopolysyndactyly Diagnosed?

• Diagnosis of acrocephalopolysyndactyly is done based on clinical examination and can be confirmed by a molecular genetic test.

• Additional imaging tests can also be done to help with the diagnosis, evaluate the bones in more detail, and study the extent of the conditions.

• Prenatal genetic screening and diagnosis can be done if there is already a known genetic mutation among the family members.

• Ultrasound of the fetus may also detect abnormal head shape, other skeletal defects, heart defects, and other symptoms.

• Through a physical examination of the patient, irregularities in head shape, facial features, and abnormalities in the structure of the hands and feet become apparent.

• Genetic testing is an essential tool for diagnosing acrocephalopolysyndactyly. Most cases of acrocephalopolysyndactyly are caused by gene mutations involved in bone development. Genetic testing can identify these mutations and help confirm the diagnosis.

How Is Acrocephalopolysyndactyly Managed?

The management of acrocephalopolysyndactyly is focused on treating the individual symptoms and complications associated with the condition. There is currently no cure for acrocephalopolysyndactyly, and the treatment is primarily supportive. Multidisciplinary treatment and management are required. Some of the treatment strategies include the following.

Surgery

• Depending on the severity and the specific subtype of the syndrome, surgery may be recommended to correct the abnormalities of the skull, face, hands, and feet.

• Early craniofacial reconstruction may be done to improve the appearance and prevent complications like breathing trouble and intellectual disability.

• Surgery is done to correct congenital heart defects.

• Shunting is done to reduce high intracranial pressure in some cases.

Other Treatments

• Other symptom-specific treatments are done for different symptoms and complications.

• Occupational therapy can help the affected individuals develop daily living skills and improve hand and finger function.

• Speech therapy is recommended for individuals who experience speech and language challenges due to craniofacial abnormalities. Orthodontic and other dental treatments are done to treat dental problems.

• Treatments and checkups are done to correct vision problems.

• Social and psychological support for the affected individuals and their families is given by counseling, support groups, etc.

Genetic Counseling

Genetic counseling is recommended for the affected individuals and their families to help them understand the inheritance pattern of the condition and the likelihood of passing it on to future generations.

What Are the Outcomes of Acrocephalopolysyndactyly?

The prognosis of the condition varies depending on the severity of the malformations and the extent of intellectual disability present. Some affected children become independent adults, and others require more support due to physical and intellectual challenges. The primary factor contributing to a shortened life expectancy is predominantly attributed to heart defects.

Conclusion

Acrocephalopolysyndactyly affects bone development in the head, hands, and feet. There are several subtypes, each with unique features and inheritance patterns. With appropriate care, individuals with acrocephalopolysyndactyly can lead fulfilling lives and achieve their full potential.