Bone: McCune-Albright syndrome: practice question

A Pathology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pathology · Bone: McCune-Albright syndrome

Sample item

A 9-year-old girl has precocious puberty, large café-au-lait macules with irregular borders and polyostotic bone lesions. Radiographs show ground-glass lesions and a shepherd's crook deformity of the femur. Which molecular defect explains the multi-system disease?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

A. Post-zygotic activating mutation of GNAS (Gs alpha), producing a mosaic state

McCune-Albright syndrome is due to a post-zygotic activating GNAS mutation, so only some cells carry constitutive Gs alpha activity. The result is polyostotic fibrous dysplasia, café-au-lait macules with a coast-of-Maine border and autonomous endocrine hyperfunction such as precocious puberty. It is not inherited because a germline mutation would be lethal.

Option by option

  • A. Post-zygotic activating mutation of GNAS (Gs alpha), producing a mosaic state (correct)

    Correct. A mosaic activating GNAS mutation explains bone, skin and endocrine features.

  • B. NF1 mutation, causing neurofibromatosis type 1

    NF1 gives café-au-lait spots with smooth borders and neurofibromas, but not fibrous dysplasia and precocious puberty.

  • C. Activating mutation of the PTH receptor, causing Jansen metaphyseal chondrodysplasia

    PTH receptor activation gives metaphyseal chondrodysplasia with hypercalcaemia and not fibrous dysplasia.

  • D. Germline inactivating mutation of GNAS, causing Albright hereditary osteodystrophy

    Germline inactivating GNAS mutation causes Albright hereditary osteodystrophy with short stature and pseudohypoparathyroidism.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pathology question

What is the answer to this Pathology question?

The best answer is A, Post-zygotic activating mutation of GNAS (Gs alpha), producing a mosaic state. McCune-Albright syndrome is due to a post-zygotic activating GNAS mutation, so only some cells carry constitutive Gs alpha activity.

Why is "NF1 mutation, causing neurofibromatosis type 1" not the answer?

NF1 gives café-au-lait spots with smooth borders and neurofibromas, but not fibrous dysplasia and precocious puberty.

Why is "Activating mutation of the PTH receptor, causing Jansen metaphyseal c…" not the answer?

PTH receptor activation gives metaphyseal chondrodysplasia with hypercalcaemia and not fibrous dysplasia.

Why is "Germline inactivating mutation of GNAS, causing Albright hereditary o…" not the answer?

Germline inactivating GNAS mutation causes Albright hereditary osteodystrophy with short stature and pseudohypoparathyroidism.

What concept does this question test?

It tests Bone: McCune-Albright syndrome in Pathology. The result is polyostotic fibrous dysplasia, café-au-lait macules with a coast-of-Maine border and autonomous endocrine hyperfunction such as precocious puberty. It is not inherited because a germline mutation would be lethal.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Bone: McCune-Albright syndrome?

Learn each disease as a bundle: cause, key histology, markers, and the clinical hallmark. Then use the flashcards and the other Pathology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.