Woodhouse-Sakati Syndrome - An Overview

Introduction

People with Woodhouse-Sakati syndrome experience hypogonadism, which is characterized by unusually low levels of the hormones that control sexual development. Affected people do not grow pubic hair, more breast tissue, a deeper voice, or other secondary sexual traits without hormone replacement medication. Females with Woodhouse-Sakati syndrome may instead have underdeveloped tissue clumps called streak gonads in place of functional ovaries. In affected females, the uterus may also be tiny or nonexistent. Males with this condition have testes that little or never generate sperm. People with Woodhouse-Sakati syndrome typically are unable to conceive as a result (of infertility).

What Is the Etiology Behind Woodhouse-Sakati Syndrome?

Mutations in the DCAF17 gene lead to Woodhouse-Sakati syndrome. The body's tissues and organs that contain the protein include the brain, skin, and liver. Most of the DCAF17 gene mutations found in individuals with Woodhouse-Sakati syndrome cause a protein that is unusually short and degrades quickly or whose normal function is compromised. Although it is unclear how a lack of this protein causes hormone imbalances and the other indications and symptoms, it is likely that loss of DCAF17 protein function accounts for the characteristics of Woodhouse-Sakati syndrome.

What Are the Symptoms Associated With Woodhouse Sakati Syndrome?

• Hypogonadism - Causes delayed puberty and a lack of secondary sexual characteristics in all affected people. Defining the nature of hypogonadism has been challenging because neither hyper- nor hypogonadotropic hypogonadism fits either group. Both conditions have been reported in roughly 30 percent of affected people. A normal sense of smell.

• Amenorrhea is a common condition in women. More than 50 of the women documented in the literature underwent thorough endocrine examinations, which often revealed drastically diminished or missing estradiol and elevated follicle-stimulating hormone and luteinizing hormone, which is consistent with hypogonadotropic hypogonadism. The follicle-stimulating and luteinizing hormones are not as high as predicted, given the extent of ovarian failure, suggesting that the hypothalamic-pituitary axis is less sensitive.

• By laparotomy, laparoscopy, or autopsy, the ovaries are not visible because they are streaky or undeveloped. An ovarian biopsy revealed fibrous tissue devoid of any discernible oocysts.

• Compared to women, males have moderately low levels of testosterone and unacceptably low levels of gonadotropins, which are consistent with hypogonadotropic hypogonadism, which may have a central or central and peripheral origin. Azoospermia may be discovered through semen analysis.

• The testes are normal size, but spermatogenesis is decreased, with more sertoli cells than Leydig cells, according to a testicular biopsy.

• The affected individual has low levels of insulin-like growth factor 1 (IGF-1). In women, IGF-1 reduction is more noticeable. Low-sex steroids due to hypogonadism may be reflected in the low IGF-1 levels.

• Sixty-six percent of the population and 96 percent of people over the age of 25 were found to have type 2 diabetes, whether it is insulin-dependent or not.

• In 30 percent of people, usually, at approximately the age of 20, peripheral hypothyroidism was discovered. This means that it was primary, and there was no sign of autoimmune etiology.

• Alopecia - Primarily, frontotemporal alopecia and thin, sparse scalp hair are present in all affected people. Alopecia totalis frequently develops at the age of the third or fourth decade. However, hair loss can start as early as childhood. Lack of or insufficient lashes and brow hair. Men have little to no facial hair.

• Some affected people also have other distinctive facial characteristics, such as a long, triangular face, widely spread eyes (hypertelorism), and a prominent nose bridge.

Neurological issues affect more than half of those with Woodhouse-Sakati syndrome.

• Affected people frequently have dystonias, a set of movement disorders that typically start in youth or young adulthood. These aberrant movements may involve twisting of particular bodily components like arm and leg or involuntary tensing of the muscles (muscle contractions).

• Other neurological traits include moderate intellectual incapacity and trouble speaking or swallowing (dysarthria).

• The hearing loss is brought on by abnormalities in the inner ear (sensorineural hearing loss). Hearing issues appear after learning the spoken language (post-lingual), typically in adolescence.

Imaging tests have revealed aberrant iron deposits in the brains of some affected people.

What Is the Genetics Behind Woodhouse-Sakati Syndrome?

Woodhouse-Sakati syndrome is thought to be brought on by mutations in the C2orf37 gene, which may be found in human chromosome 2q22.3-q35. The condition is inherited autosomally recessively. This indicates that one defective gene copy is inherited from each parent, making a total of two copies necessary for a person to be born with the disorder. An autosome (chromosome 2) contains the faulty gene that causes the illness. One copy of the defective gene is present in both parents of a person with an autosomal recessive disorder, but they typically do not exhibit any signs or symptoms of the condition.

How Is Woodhouse-Sakati Syndrome Diagnosed?

1. Iron buildup in the brain is identified using a T2-sequence MRI.

2. A blood test can also find low insulin-like growth factor 1.

3. Genetic testing of the DCAF17 gene is necessary for the diagnosis of Woodhouse-Sakati syndrome because it looks for two specific gene alterations.

4. Sequence analysis is the first step in the testing process, followed by deletion and duplication analysis if no changes are discovered.

The outcome of brain MRI neuroimaging

1. A little pituitary gland and a relatively empty sella.

2. Frontoparietal or periventricular white matter lesions that are advancing.

3. Buildup of iron in the globus pallidus and, to a lesser degree, in the substantia nigra and red nucleus.

4. Rarely, the corpus callosum's splenium may have large perivascular gaps and diffusion restrictions.

What Are the Treatment Modalities for Treating Woodhouse-Sakati Syndrome?

Treatment of Manifestations:

• Hormone replacement therapy is necessary for hypogonadism in order to promote bone health and secondary sex characteristics at the typical age of puberty.

• Alopecia is only treated with symptomatic medicine for aesthetic purposes.

• Dystonia is often treated with oral medicines, followed in some cases with Botulinum toxin injections and/or deep brain stimulation.

• A speech therapist's advice is frequently helpful for those with dysarthria.

• To maintain caloric intake, people with dysphagia frequently need to take steps to minimize oral secretions, use thickened liquids and pureed foods to prevent aspiration, and finally undergo a gastrostomy.

• Standard care for intellectual impairment, hypothyroidism, diabetes mellitus, and hearing loss.

Observation for Endocrine Abnormalities is Advised Starting at the Following Ages:

• Hypogonadism starts at 12 to 14 years of age.

• Diabetes mellitus and hypothyroidism, starting at 20 years of age.

• Serum IGF-1 every three to five years after diagnosis.

• Dystonia, starting with an annual neurologic assessment.

• Dysarthria and dysphagia, starting at an annual speech and language assessment.

Conclusion

The body's network of glands that produce hormones is known as the endocrine system, and the neurological system are the two main areas of the body affected by the Woodhouse-Sakati syndrome. Almost all people with Woodhouse-Sakati syndrome have hypogonadism, which becomes apparent throughout puberty and increasing childhood-onset hair thinning that frequently develops into alopecia totalis in adulthood. Progressive extrapyramidal movements (dystonic spasms with dystonic posturing with dysarthria and dysphagia), minor intellectual disability, and moderate bilateral postlingual sensorineural hearing loss affect more than half of the population. For Woodhouse-Sakati syndrome, there is no specific treatment. Symptom relief is the goal of treatment.