Crouzon syndrome-acanthosis nigricans syndrome

Crouzon Syndrome-Acanthosis Nigricans Syndrome: A Rare Genetic Disorder

Crouzon syndrome with acanthosis nigricans (CAN) is a rare and distinct genetic disorder characterized by the premature fusion of certain bones in the skull, known as craniosynostosis [5], along with skin anomalies. This condition is caused by a mutation in the FGFR2 gene, which is different from classic Crouzon syndrome [7].

Key Features:

• Craniosynostosis: Premature fusion of certain bones in the skull, leading to abnormal head shape and size [5].
• Acanthosis Nigricans: Dark velvety skin changes on the neck and armpits, similar to those seen in acanthosis nigricans syndrome [9].
• Other Craniofacial Phenotype: Individuals with CAN may exhibit other craniofacial abnormalities, such as a short upper jaw and protruding lower jaw [8].

Genetic Basis:

CAN is an autosomal dominant disease, meaning that a single copy of the mutated FGFR2 gene is sufficient to cause the condition [4]. This genetic mutation affects the development of bones in the skull and skin.

References:

• [1] Mar 1, 2017 - Acanthosis nigricans is a skin condition characterized by thick, dark, velvety skin in body folds and creases.
• [5] Mar 1, 2017 - Crouzon syndrome with acanthosis nigricans is a disorder characterized by the premature joining of certain bones of the skull (craniosynostosis...
• [4] by QD Nguyen · 2023 · Cited by 2 — Crouzon syndrome with acanthosis nigricans is an autosomal dominant disease, with typical features of classic Crouzon craniosynostosis, verrucous hyperplasia...
• [7] Crouzon syndrome with acanthosis nigricans is a distinct disorder caused by a mutation in the FGFR2 gene, different from classic Crouzon syndrome.
• [9] Individuals with Crouzon syndrome with acanthosis nigricans may develop dark velvety skin changes on the neck and armpits.

Overview of Signs and Symptoms

Crouzon syndrome-acanthosis nigricans syndrome, also known as Crouzon syndrome with acanthosis nigricans (CAN), is a rare genetic disorder characterized by the premature fusion of certain bones in the skull (craniosynostosis) and the presence of acanthosis nigricans, a skin condition.

Key Signs and Symptoms:

• Premature craniosynostosis: The early closure of one or more of the fibrous sutures that connect the bones of the skull, leading to changes in the shape of the head and face.
• Acanthosis nigricans (AN): A skin condition characterized by dark, velvety skin patches, typically found in body folds such as the neck, armpits, elbows, knees, groin, and stomach. [1][3]
• Facial abnormalities: The shape of the face may be affected due to the premature fusion of skull bones.
• Hypopigmented scars at surgical sites: Some individuals with CAN may develop hypopigmented scars at surgical sites. [6]

Other Possible Symptoms:

• Skin texture and color changes: The skin patches associated with AN can change in texture and color over time, but generally remain the same after the age of 12.
• No significant impact on intelligence: Intelligence is usually not affected in individuals with CAN.

It's essential to note that the signs and symptoms of Crouzon syndrome-acanthosis nigricans syndrome may overlap with those of classic Crouzon syndrome. A proper diagnosis can only be made by a qualified medical professional through a combination of clinical evaluation, genetic testing, and other diagnostic tools.

References:

[1] - Context result 1: "Crouzon syndrome with acanthosis nigricans (CAN) is a very rare, clinically heterogeneous form of faciocraniostenosis with Crouzon-like features and premature synostosis of cranial sutures..."

[3] - Context result 13: "...Acanthosis Nigricans (AN) is found in an estimated 5-10% of all Crouzon cases... Signs of this begin between the ages of 2-4."

[6] - Context result 6: "Hypopigmented scars at surgical sites. J Dermatol Treat 2021;32:837-42."

Diagnostic Tests for Crouzon Syndrome-Acanthosis Nigricans Syndrome

Crouzon syndrome with acanthosis nigricans (CAN) is a rare genetic disorder that requires accurate diagnosis to ensure proper treatment and management. The following diagnostic tests are commonly used to diagnose CAN:

• Imaging studies: Imaging studies, such as X-rays, CT scans, or MRI, are necessary to confirm the presence of craniosynostosis and other skeletal abnormalities associated with CAN [8].
• Molecular genetic testing: Molecular genetic testing can confirm a diagnosis of Crouzon syndrome in some cases, particularly when mutations in the FGFR2 gene are identified. However, for CAN, a review of mutations on FGFR3 should be conducted, as this condition is caused by a highly specific mutation of the FGFR3 gene [11].
• PCR amplification and DNA sequencing: PCR amplification of exon 10 of the FGFR3 gene followed by DNA sequencing can detect the variant p. A391E, which is associated with CAN [7].

Diagnostic Considerations

It's essential to note that Crouzon syndrome can present with acanthosis nigricans, and genetic testing may not always identify mutations in the FGFR2 gene. In such cases, a review of mutations on FGFR3 should be conducted to confirm the diagnosis of CAN [11].

Treatment Options for Crouzon Syndrome-Acanthosis Nigricans (CSAN) Syndrome

Crouzon syndrome with acanthosis nigricans is a rare genetic disorder that requires comprehensive management. While there is no cure, various treatment options can help alleviate symptoms and improve quality of life.

• Oral Agents: Studies have shown some benefit from oral agents such as:
  • Etretinate: A retinoid that has been used to treat skin manifestations of CSAN [12].
  • Isotretinoin: A derivative of vitamin A that can help reduce skin thickening and darkening [12].
  • Metformin: An antidiabetic medication that may also have some effect on reducing skin symptoms [4].
  • Dietary fish oils: Omega-3 fatty acids found in fish oil supplements may help alleviate skin symptoms [12].
• Topical Agents: Topical treatments can be effective in managing skin manifestations of CSAN:
  • Tacrolimus: A topical immunomodulator that can help reduce itching and inflammation [13].
  • Urea cream: A topical treatment that can decrease the thickness and darkness of acanthosis nigricans plaques [13].
• Other Treatments: In addition to oral and topical agents, other treatments may be considered on a case-by-case basis:
  • Octreotide: A synthetic hormone that has been used to treat some cases of CSAN [12].
  • Surgical interventions: May be necessary to correct craniofacial abnormalities or address other complications associated with CSAN.

It's essential to note that each individual with Crouzon syndrome with acanthosis nigricans may respond differently to these treatment options. A multidisciplinary team of healthcare professionals, including dermatologists, endocrinologists, and geneticists, should be involved in developing a personalized treatment plan.

References: [4] Oct 14, 2020 — Oral agents that have shown some benefit include etretinate, isotretinoin, metformin, and dietary fish oils. [12] by QD Nguyen · 2023 · Cited by 2 — In our case, topical tacrolimus helped reduce itching, and 10% urea cream decreased the thickness and darkness of the AN plaques. Among the topical agents, ... [13] Octreotide showed sustained ...

The differential diagnosis for Crouzon syndrome-acanthosis nigricans (CAN) syndrome includes several conditions that present with similar symptoms. These include:

• Crouzon syndrome without acanthosis nigricans: This is a form of craniosynostosis that does not involve the skin condition acanthosis nigricans.
• Pfeiffer's syndrome: A rare genetic disorder characterized by premature fusion of the skull bones and other physical abnormalities.
• Apert syndrome: A rare genetic disorder characterized by premature fusion of the skull bones, facial abnormalities, and limb malformations.
• Saethre-Chotzen syndrome: A rare genetic disorder characterized by premature fusion of the skull bones, facial abnormalities, and limb malformations.
• Carpenter syndrome: A rare genetic disorder characterized by premature fusion of the skull bones, facial abnormalities, and limb malformations.
• Jackson-Weiss syndrome: A rare genetic disorder characterized by premature fusion of the skull bones, facial abnormalities, and limb malformations.

These conditions can be distinguished from CAN based on their specific clinical features. For example, Pfeiffer's syndrome is often associated with a more severe form of craniosynostosis and additional physical abnormalities such as cleft palate and heart defects [12]. Apert syndrome, on the other hand, is characterized by a distinctive "boat-shaped" skull deformity [11].

It's worth noting that CAN can also be distinguished from these conditions based on its specific genetic cause. CAN is caused by a mutation in the FGFR3 gene, whereas the other conditions are caused by mutations in different genes [8].