autosomal dominant Wolfram syndrome

Autosomal Dominant Wolfram Syndrome

Autosomal dominant Wolfram-like syndrome (WFSL) is a rare genetic disorder characterized by the clinical triad of congenital progressive hearing impairment, diabetes mellitus, and optic atrophy [1]. This condition is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the disease.

Key Features:

• Congenital progressive hearing impairment
• Diabetes mellitus (insulin-dependent)
• Optic atrophy (progressive loss of vision)

Other features may include:

• Deafness
• Diabetes insipidus
• Progressive loss of vision

Autosomal dominant Wolfram syndrome is a rare and severe condition that affects multiple systems in the body. It is caused by a mutation in one of the genes responsible for the disease, which is inherited from an affected parent.

References:

[1] Congenital progressive hearing impairment, diabetes mellitus, and optic atrophy are key features of autosomal dominant Wolfram-like syndrome (WFSL) [1]. [7] Autosomal dominant Wolfram syndrome is a genetic disorder characterized by progressive hearing loss, diabetes mellitus, and optic atrophy. It is caused by a mutation in one of the genes responsible for the disease [7].

Based on the provided context, here are the signs and symptoms of autosomal dominant Wolfram syndrome:

• Deafness [5]
• Optic atrophy [4][7]
• Diabetes mellitus [4][7]
• Diabetes insipidus [7]

Note that these symptoms may not be exhaustive, as the context mentions "other reported symptoms" but does not specify them. However, based on the information provided, the above-mentioned symptoms are associated with autosomal dominant Wolfram syndrome.

References: [5] - Autosomal dominant mutations in the WFS1 gene have however been implicated in Wolfram-like syndrome, characterized by deafness, optic atrophy ... [4] - Classical WS features are childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus, neurological signs, and other ... [7] - Additional manifestations include diabetes insipidus, hypogonadism, optic atrophy and neural deafness.

Based on the provided context, it appears that diagnostic testing for autosomal dominant Wolfram syndrome involves genetic screening and sequencing.

• Genetic screening can confirm the diagnosis of autosomal dominant Wolfram syndrome by identifying mutations in the WFS1 gene [5].
• Sanger sequencing-based genetic testing of the WFS1 gene is a common method used to confirm the diagnosis, which usually identifies recessive mutations in the majority of patients [5].
• Diagnostic testing must be carried out within a laboratory environment working to standards compliant with the ISO 15189 [9].
• Genetic tests, such as exome sequencing and genome sequencing-based diagnostic methods, are valuable tools to confirm or rule out the diagnosis of WS1 [13].

It's worth noting that autosomal dominant Wolfram syndrome is a rare form of the condition, and some cases may have an autosomal recessive inheritance pattern. However, in cases where it is suspected due to childhood-onset diabetes mellitus and optic atrophy, diagnostic testing can be used to confirm the diagnosis [14].

References: [5] Sanger sequencing-based genetic testing of the WFS1 gene usually confirms the diagnosis. [9] Diagnostic testing must be carried out within a laboratory environment working to standards compliant with the ISO 15189. [13] Genetic tests, such as exome sequencing and genome sequencing-based diagnostic methods, are valuable tools to confirm or rule out the diagnosis of WS1. [14] Diagnosis is suspected in cases of childhood-onset diabetes mellitus and optic atrophy, and this visual impairment is not due to the diabetes.

Based on the available information, it appears that there are no specific drug treatments mentioned for autosomal dominant Wolfram syndrome.

However, research suggests that chemical chaperones such as 4-phenylbutyric acid and tauroursodeoxycholic acid may be beneficial in mitigating ER stress, which is a key feature of Wolfram syndrome [1][2]. These drugs work by rescuing or stabilizing misfolded proteins, thereby reducing the burden on the endoplasmic reticulum.

It's also worth noting that gene therapy using adeno-associated viral (AAV) systems has been proposed as a potential approach to treating Wolfram syndrome [3]. This involves delivering healthy copies of the WFS1 or CISD2 genes to cells, which could potentially restore normal function and alleviate symptoms.

Unfortunately, there is no specific mention of drug treatments for autosomal dominant Wolfram syndrome in the available information. However, research into chemical chaperones and gene therapy may provide some hope for future therapeutic options.

References:

[1] by F Urano · 2016 · Cited by 277 — Thus, targeting drugs known to maintain ER calcium levels during ER stress presents a novel therapeutic target for Wolfram syndrome. [2] by D Abreu · 2019 · Cited by 52 — Chemi- cal chaperones, such as 4-phenylbutyric acid and tauroursodeoxycholic acid, are drugs that are known to mitigate. ER stress by rescuing or stabilizing ... [3] by D Abreu · 2019 · Cited by 52 — One of the approaches to provide a cure to Wolframs syndrome could be via gene therapy. Using adeno-associated viral (AAV) systems, wild-type ...

The differential diagnosis for autosomal dominant Wolfram syndrome includes several conditions that present with similar symptoms. Some of these conditions are:

• Mitochondrial disorders: These can include maternally inherited diabetes-deafness syndrome (MIDD) and Leber Hereditary Optic Neuropathy, which can cause deafness, optic atrophy, and other systemic problems [1][8].
• Autosomal dominant optic nerve atrophy: This is a condition that affects the optic nerves and can cause progressive vision loss. It is often associated with other systemic problems, including diabetes insipidus and deafness [3][8].
• Diabetic papillopathy: This is a condition that causes changes in the retina of people with diabetes, which can be mistaken for other conditions such as optic atrophy.
• Cerebellar atrophy with superior vermian predominance: This is a rare condition that affects the cerebellum and can cause problems with coordination and balance. It is often associated with other systemic problems, including optic atrophy [6].

It's worth noting that the differential diagnosis for autosomal dominant Wolfram syndrome is complex and requires careful consideration of multiple factors. A thorough medical evaluation and diagnostic testing are necessary to accurately diagnose this condition.

References: [1] by F Urano · 2016 · Cited by 277 [3] Another name for the syndrome is DIDMOAD, which is an acronym for diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. [6] by MT Pallotta · 2019 · Cited by 119 [8] by F Urano · 2016 · Cited by 277