FaCD Online Syndrome Fact Sheet

Last updated: 13 May 2010

Name: Alpha-Fetoprotein, Hereditary Persistence of

Synonym: HPAFP

Mode of Inheritance: AD

Genes

AFP, mapped to 4q11-q13

Tumor features (possible)

non-seminoma
seminoma

Non-tumor features

increased/persistent serum AFP

Comment

This disorder is characterized by the persistence of high AFP, due to a mutation in the AFP gene[1;2;7]. Staples et al.[3] reported high serum AFP in a 23-year-old man with a testicular seminoma as well as in his 3 sisters, mother and maternal aunt. He also had hereditary spherocytosis. Hart et al.[4] and Cochran et al.[5]. reported a yolk sac tumor in a 20-year-old male and a 20-month-old male with HPAFP, respectively. Although the association is probably purely coincidental, it is important to stress that HPAFP may confuse management in patients with a testicular or liver tumors, or other conditions where AFP levels are of diagnostic or screening importance. If HPAFP is not recognized in these conditions, then this may lead to inappropriate medical decisions. HPAFP has been observed in familial testicular cancer cases[6]. Testing parental levels of AFP has been advised for cases where persistent (mild) elevation of AFP following resection of localized germ cell tumors has been observed, before deciding on chemotherapy[5].

References

[1] McVey JH, Michaelides K, Hansen LP, Ferguson-Smith M, Tilghman S, Krumlauf R, Tuddenham EG. A G-->A substitution in an HNF I binding site in the human alpha- fetoprotein gene is associated with hereditary persistence of alpha-fetoprotein (HPAFP). Hum Mol Genet 1993; 2(4):379-384.
[2] Schefer H, Mattmann S, Joss RA. Hereditary persistence of alpha-fetoprotein - Case report and review of the literature. Ann Oncol 9[6], 667-672. 1998.
[3] Staples J. Alpha-fetoprotein, cancer and benign conditions. Lancet 1986; II:1277.
[4] Hart PS, Nanton JR, Vlaservich AC, Berry MN, Chauvenet A. Hereditary persistence of alpha-fetoprotein and testicular cancer in a 20 month old male. Am J Hum Genet 1997; 61(4):A68.
[5] Cochran PK, Chauvenet AR, Hart PS, de Graaf SSN, Cushing B, Kroovand L, Wofford MM. Misleading leads. Hereditary persistence of alpha-fetoprotein in a child with testicular germ cell tumor. Med Pediatr Oncol 32, 436-437. 1999.
[6] Platini C. [Hereditary persistence of alpha-fetoprotein: report of a case]. La Revue de médecine interne 2002; 23(2):182-8.
[7] Li X, Alexander S. Hereditary persistence of alpha-fetoprotein. Pediatr Blood Cancer. 2009 Mar;52(3):403-5.