Lentiginoses Syndromes

Question 1

What does LEOPARD syndrome stand for?

Answer 1

Lentigines

ECG defects

Ocular hypertelorism

Pulmonic stenosis

Abnormal genitalia

Retardation of growth

Deafness-sensorineural

Question 2

What are the mutations and mode of inheritance seen in LEOPARD syndrome?

Answer 2

Missense mutations in PTPN11/SHP2 (90%), RAF1 mutations (3%)

AD

Question 3

What are the cutaneous findings of LEOPARD syndrome?

Answer 3

• Lentigines involving the face, neck, and upper trunk are
  the most common presenting feature (86%) and develop at 4–5 years of age as pinpoint to 5-mm brown-black macules
• Café noir spots larger and more pigmented
• Numerous café-au-lait macules
• Abnormal dermatoglyphics

Question 4

What are the extracutaneous findings associated with LEOPARD syndrome?

Answer 4

Hypertrophic cardiomyopathy (71%)

Facial dysmorphism

Genital abnormalities - gonadal hypoplasia, cryptorchidism, delayed puberty and hypospadias

• Skeletal–mandibular prognathism and short stature

and joint hyperextensibility

Granular cell myoblastomas

Question 5

What are the two other names within the Carney complex?

Answer 5

NAME and LAMB

Question 6

What does NAME and LAMB stand for?

Answer 6

Nevi

Atrial -

Myxomas

Ephelids

Lentigines

Atrial -

Myxomas

Blue

Nevi

Question 7

What is the mutation involved and the mode of ineheritance in the Carney complex (NAME and LAMB)?

Answer 7

PRKAR1A (50%)

Some can have changes @ chromosome 2p16

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Question 8

What are the clinical findings in Carney complex (NAME and LAMB)?

Answer 8

Epithelioid blue nevi (Very important and SPECIFIC)

Periorificial lentigines are seen in 77%; fade with time

Blue nevi are seen in 43%; fade with time

(highly specific) Cutaneous myxomas

Café au lait macules

Skin myxomas involving the eyelids, ear, nipple, breast, and mucosa are seen in 33%

Question 9

Extracutaneous findings in Carney complex (NAME and LAMB)?

Answer 9

Cardiac myxomas (50%–80%; may embolize), Endocrine neoplasms, especially primary pigmented adrenocortical disease (26%–45%) Sertoli cell tumor seen in 33%
Thyroid nodules/carcinoma
- Psammomatous melanotic schwannoma

• Breast ductal carcinoma

Question 10

What is the mutation and mode of inheritance in Peutz-Jeghers syndrome?

Answer 10

Serine/Threonine kinase (STK11/LBK1) [70%]

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Question 11

What is the clinical appearance of Peutz-Jeghers syndrome?

Answer 11

Pigmented macules on lips, buccal mucosa, digits, and other mucosa are seen in 50%–60% by age 20

• May fade with time
• No relationship between severity of pigmentation and polyps

Question 12

Extracutaneous findings in Peutz-Jeghers syndrome?

Answer 12

GI polyps, most common in the jejunum and ileum: These can lead to intussusception (most common), GI bleeding, anemia, and vomiting

• 93% develop cancer before age 65: GI most common (small intestine, stomach, esophagus, colon or pancreas), lung, and breast

Adenocarcinoma seen in younger patients

Question 13

What is the clinical presentation of Laugier-Hunziker?

Answer 13

Pigmented macules on lips, buccal mucosa, genitals, and other mucosa
Melanonychia in ~50%

Question 14

Is there an increased risk of cancer in Laugier-Hunziker?

Answer 14

No

Question 15

What are the clinical manifestations of Cronkhite-Canada syndrome?

Answer 15

Lentigines of hands, feet, and buccal mucosa
- Nail dystrophy
- Alopecia

Question 16

Extracutaneous findings in Cronkhite-Canada?

Answer 16

Intenstinal Polyposis

Question 17

What is the gene and inheritance pattern in Centrofacial lentiginosis (Touraine’s syndrome)?

Answer 17

Gene unknown

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Question 18

Cutaneous findings in Centrofacial lentiginosis (Touraine’s syndrome)?

Answer 18

Lentigines in the first year of life, especially on nose adn cheeks

• Sacral hypertrichosis

Question 19

Extracutaneous findings in Centrofacial lentiginosis (Touraine’s syndrome)?

Answer 19

Developmental delay, congenital mitral valve stenosis, seizures, absent middle incisors, skeletal abnormalities, Dwarfism, Endocrine dysfunction

Question 20

What is the gene and mode of inheritance for Bannayan-Riley Ruvalcaba syndrome?

Answer 20

PTEN

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Question 21

What cutaneous findings are seen in Bannayan-Riley Ruvalcaba syndrome?

Answer 21

Lipomas

Penile lentigines

Question 22

Extracutaneous findings in Bannayan-Riley Ruvalcaba syndrome?

Answer 22

Macrocephaly

Vascular anomalies–deep, high flow

Developmental delay

Intestinal polyps

Macrodactyly

Pseudopapilledema

Hashimoto thyroiditis

Increased risk of malignancy