Hartsfield syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at October 23, 2016
StartDiseasesHartsfield syndrome

Children born with Hartsfield syndrome face many challenges because of the symptoms associated with the condition. Although it occurs rarely, this disease has a dramatic effect on the lives of the people affected by it.

Contents

Definition & Facts

Hartsfield syndrome is a condition in which the patient suffers from a combination of holoprosencephaly and ectrodactyly. Holoprosencephaly is a brain deformity wherein the frontal portion of the brain does not properly split into two distinct hemispheres during embryonic development.

Ectrodactyly is a condition indicated by missing fingers and/or toes and a fusion of the digits that do exist. This occurs more often in the hands and is often called “lobster claw” syndrome because of the affected hand’s resemblance to the crustacean’s claw. Hartsfield syndrome is a devastating but extremely rare disease. Fewer than 20 cases have been recorded.

Symptoms & Complaints

<html>

</html>

SecurePHP: Permission error <html></div></html> Because patients with Hartsfield syndrome suffer from both holoprosencephaly and ectrodactyly, the symptoms they exhibit can be numerous. The brain deformity can cause an array of problems, ranging from mild to severe.

Intellectual disability is not uncommon among these patients. They can also suffer from congenital heart defects, seizures, spasms, difficulty eating, and/or difficulty breathing, and the inability to properly regulate body temperature and maintain consistent sleep patterns.

The pituitary gland, which produces several hormones the body needs in order to function properly, is often affected. The malfunctioning pituitary gland can cause a number of issues. These problems include an insufficient level of growth hormone that leads to slow physical development, a deficiency in the hormones that initiate and sustain the development of the sex organs, and diabetes insipidus that causes an imbalance of fluids within the body.

Besides the skeletal abnormalities associated with ectrodactyly, those with Hartsfield syndrome can also exhibit other physical characteristics. The most common of these is a cleft lip and cleft palate, which is when there is a split in the lip and an opening in the palate or roof of the mouth. Hartsfield patients often have very widely spaced eyes and/or ears that are closely spaced and smaller than normal. 

Causes

Research has shown that Hartsfield syndrome is caused by a mutation of a specific gene called FGFR1 (fibroblast growth factor receptor 1). This gene produces a protein receptor that interacts with specific proteins called fibroblast growth factors, or FGFs. The FGFR1 is essential in the development of many parts of the body, including the brain, the craniofacial bones (bones of the skull and face), and the hands and feet.

Because the connection between the receptors and the proteins is incomplete, the proper signals are not sent to the appropriate cells. There are some cases of Hartsfield syndrome in which no FGFR1 mutation is present. The cause of the condition in these instances remains unknown.

The mutation that causes Hartsfield syndrome can be passed to the patient through either autosomal dominant inheritance or autosomal recessive inheritance. Autosomal dominance means that either one parent passes on the mutation. In the cases of autosomal dominant inheritance, the FGFR1 mutation is usually new – or de novo – and occurs either in the creation of the eggs or sperm or during early development of the embryo in the womb. In autosomal recessive inheritance, each parent passes a copy of the mutated gene to the child but do not show signs of the disorder themselves.

Diagnosis & Tests

The diagnosis of Hartsfield syndrome includes the recognition of symptoms associated with both holoprosencephaly and ectrodactyly. Molecular genetic testing of the patient can be used to confirm both the presence of the FGFR1 mutation and the method of inheritance.

Forms of molecular genetic testing include single-cell and multi-cell testing. In single-cell genetic testing for Hartsfield syndrome, only the FGFR1 is tested for mutation. In multi-cell genetic testing, other cells are tested along with the FGFR1 gene in order to determine if related abnormalities exist. For example, related mutations of KAL1 gene and Xq24 have been found in Hartsfield syndrome patients. These discoveries indicated that these patients’ symptoms did not result from the gene mutation associated with Hartsfield syndrome. Thorough genetic testing can prevent physicians from incorrectly diagnosing other conditions as Hartsfield syndrome.

Prenatal testing is available to diagnosis the condition in utero.

Treatment & Therapy

The treatment of Hartsfield syndrome involves various drugs to deal with the wide range of symptoms associated with the disease. Anti-epileptic drugs can help to prevent the seizures patients typically suffer through, and muscle relaxants can help to alleviate the spasms.

Physical therapy and the use of braces can also help with the spasms but surgery is sometimes necessary. The drug desmopressin can be used to treat any occurrences of diabetes insipidus since it acts a substitute for vasopressin, the hormone that reduces urine production.

Problems with body temperature regulation can be addressed by altering the patient’s physical surroundings, such as room temperature and necessary protective clothing. Melatonin and the sleep aid clonidine can be prescribed if issues with inconsistent sleep patterns are not addressed by a change in routine. Some patients also require a gastrostomy or tracheostomy to assist with feeding or breathing difficulties.

Mild to severe mental retardation often associated with the condition cannot be treated with drugs, therapy, or surgery. That is not to say that the patients experiencing the milder version of the retardation cannot benefit from special education, speech therapy, and physical therapy.

Prevention & Prophylaxis

<html>
<p style="float:right; margin:10px;"></html>

SecurePHP: Permission error

<html>
</html>

Due to the hereditary nature of Hartsfield syndrome, the key to preventing the disease is found in genetic testing. Genetic testing can allow parents to have information about the risk that their child will have this condition. In autosomal recessive inheritance, in which both parents must pass the mutated gene on to the child, the risks are as follows:

  • 25% chance the child will be affected.
  • 50% chance the child will be an unaffected genetic carrier, showing no symptoms or signs.
  • 25% the child will be unaffected and not a carrier.
As research continues, more information about the mutation that causes Hartsfield syndrome is available. With the availability of genetic testing, the prevention of diseases like Hartsfield syndrome has become more possible.