Random Dermatology MCQ - LAMB syndrome

A 30-year-old woman presents with a history of multiple, darkly pigmented skin lesions since childhood and recurrent episodes of palpitations and syncope. Echocardiography reveals a left atrial mass. On cutaneous examination, she is noted to have dozens of small, blue-black macules and papules on her face and trunk, as well as several larger, tan, plaque-like lesions on her back. Which of the following is the most accurate description of the clinical syndrome and its underlying genetic basis?

A. LAMB syndrome, which is part of the spectrum of Carney complex and is associated with mutations in the PRKAR1A gene.
B. NAME syndrome, which is a distinct entity from Carney complex and has no known genetic basis.
C. McCune-Albright syndrome, caused by postzygotic GNAS1 mutations.
D. Neurofibromatosis type 1, caused by mutations in the NF1 gene.
E. Peutz-Jeghers syndrome, caused by mutations in the STK11 gene.

Correct Answer: A. LAMB syndrome, which is part of the spectrum of Carney complex and is associated with mutations in the PRKAR1A gene.

Answer and Explanation

The correct answer is A. This question describes a patient with the classic features of LAMB syndrome: Lentigines, Atrial Myxoma, and Blue nevi. The larger, tan plaque-like lesions are likely café-au-lait macules or other melanocytic lesions. LAMB syndrome, along with the similar NAME syndrome (Nevi, Atrial Myxoma, Myxoid neurofibromata, Ephelides), is now recognized as part of the phenotypic spectrum of Carney complex. Therefore, it shares the same underlying genetic basis: inactivating mutations in the PRKAR1A tumor suppressor gene on chromosome 17q.

Why the Other Options are Incorrect:

• B. NAME syndrome... has no known genetic basis: This is incorrect. While NAME syndrome was historically described separately, it is now understood to be a variant presentation of Carney complex and is therefore caused by the same PRKAR1A mutations. The distinction between LAMB and NAME is largely historical and phenotypic; they are not distinct genetic entities.

• C. McCune-Albright syndrome: This is characterized by polyostotic fibrous dysplasia, café-au-lait macules, and endocrine hyperfunction (e.g., precocious puberty). It is not associated with cardiac myxomas or blue nevi. The genetic defect is an activating mutation in GNAS1.

• D. Neurofibromatosis type 1: This is characterized by café-au-lait macules, axillary freckling, and neurofibromas. Blue nevi are not a typical feature, and cardiac myxomas are not part of the syndrome.

• E. Peutz-Jeghers syndrome: This features mucocutaneous melanotic macules (on lips, buccal mucosa) and gastrointestinal hamartomatous polyps. While lentigines are present, they are peri-orificial, and the syndrome is not associated with cardiac myxomas or blue nevi. It is caused by mutations in STK11.

Additional High-Yield Information for Exams:

• Integration into Carney Complex: Modern classification subsumes LAMB and NAME syndromes under Carney complex. The diagnostic criteria for Carney complex include the specific findings of spotty pigmentation (lentigines, blue nevi), cardiac myxoma, and endocrine overactivity, among others. Recognizing LAMB as a presentation of Carney complex is crucial for triggering appropriate genetic counseling and systemic surveillance.

• Key Cutaneous Features:

  • Lentigines: Small, dark brown to black macules, often on the central face, lips, conjunctiva, and genital mucosa. Their presence in non-sun-exposed areas is a clue.

  • Blue Nevi: Multiple, often epithelioid blue nevi. The presence of multiple blue nevi, especially in unusual locations, should raise suspicion for Carney complex.

  • Café-au-Lait Macules: Also common.

• Differential Diagnosis: The combination of cardiac myxoma and specific pigmented lesions primarily differentiates it from other lentiginosis syndromes (LEOPARD, Peutz-Jeghers) and other causes of cardiac tumors.

• Prognosis: The prognosis is heavily dependent on complications from cardiac myxomas, which can cause embolic stroke, heart failure, or sudden death. Endocrine tumors and rare malignancies (e.g., psammomatous melanotic schwannoma) also contribute to morbidity.

• Management & Rationale:

  • Rationale: The goal is to prevent mortality from cardiac myxoma-related complications and to screen for/manage associated endocrine and other tumors.

  • First-line/Obligatory Surveillance:

    • Annual Echocardiogram: For life, to detect cardiac myxomas. More frequent imaging may be needed post-resection or with a history of recurrence.

    • Endocrine Screening: Regular screening for Cushing's syndrome (from PPNAD), acromegaly, and thyroid cancer.

    • Genetic Counseling and Testing: For the patient and at-risk family members for PRKAR1A mutations.

  • Treatment: Prompt surgical excision of cardiac myxomas is indicated. Management of endocrine disorders is specific to the condition (e.g., adrenalectomy for PPNAD).