Howel Evans Syndrome

Question 1

What is the inheritance pattern of Howel-Evans Syndrome?

Answer 1

Autosomal dominant; RHBDF2 on 17q25; fully penetrant skin changes

RHBDF2 gene mutation is linked to the syndrome.

Question 2

How can prenatal diagnosis of Howel-Evans Syndrome be performed?

Answer 2

DNA analysis if mutation known in family

This allows for early detection in at-risk pregnancies.

Question 3

What is the incidence of Howel-Evans Syndrome?

Answer 3

Rare; less than 1 in 1,000,000; M = F

The condition affects both males and females equally.

Question 4

At what age does keratoderma typically present in Howel-Evans Syndrome?

Answer 4

Late onset (age 5-15 years)

The initial skin symptoms usually appear in childhood.

Question 5

What type of cancer is associated with Howel-Evans Syndrome and when does it typically occur?

Answer 5

Esophageal carcinoma after third decade

This cancer develops significantly later in life.

Question 6

What does the RHBDF2 gene encode?

Answer 6

Rhomboid protein RHBDL6, a serine protease

This protein regulates epidermal growth factor receptor (EGFR) and mitochondria.

Question 7

What are key skin features of Howel-Evans Syndrome?

Answer 7

Focal, on weight-bearing areas of friction, symmetric, non-transgrediens, nonepidermolytic, PPK (tylosis); digital clubbing in advanced cases; follicular hyperkeratosis

These features are critical for diagnosis.

Question 8

What gastrointestinal symptoms are associated with Howel-Evans Syndrome?

Answer 8

White, polypoid (2-5 mm) hyperkeratosis throughout esophagus; esophageal squamous cell carcinoma (ESCC); dysphagia, odynophagia, anorexia, hoarseness

These symptoms can significantly affect quality of life.

Question 9

What oral manifestation is commonly seen in Howel-Evans Syndrome?

Answer 9

Oral leukoplakia in many

This condition may indicate a risk for malignancy.

Question 10

What is a differential diagnosis for Howel-Evans Syndrome?

Answer 10

PPK with esophageal carcinoma (acquired)

This helps distinguish it from other conditions.

Question 11

What laboratory data is recommended if PPK presents with family gastrointestinal cancer history?

Answer 11

Endoscopy

This procedure is crucial for early detection of potential malignancies.

Question 12

What is the management protocol for Howel-Evans Syndrome if a mutation and/or family history is confirmed?

Answer 12

Referral to gastroenterologist—periodic endoscopic evaluation, oral cavity examination

Ongoing surveillance is important for cancer prevention.