Genetics of FIPA
FIPA has two known genetic causes, mutations in the AH receptor-interacting protein (AIP) gene and duplications in chromosome Xq26.3 that include the GPR101 gene that also causes X-linked acrogigantism (X-LAG) syndrome. About 15-20% of FIPA families carry a germline AIP gene mutation or deletion, and the disease occurs as autosomal dominant with incomplete penetrance, meaning that about 20% of AIP mutation carriers will develop a pituitary adenoma. AIP mutation associated pituitary adenomas (either presenting as FIPA or as individual, non familial cases) are usually growth hormone-secreting (acromegaly) or prolactin-secreting (prolactinoma) adenomas that are large (macroadenomas) and often occur in children, adolescents and young adults. Daly and colleagues showed that acromegaly cases with AIP mutations occurred about 20 years before acromegaly cases without AIP mutations and these tumors are large and relatively treatment-resistant. Due to their young age at onset, AIP mutations are the most frequent genetic cause of pituitary gigantism (29% of cases).X-LAG is a rare syndrome of very early childhood onset pituitary tumors/hyperplasia that leads to growth hormone excess and severe overgrowth and pituitary gigantism. Three FIPA families with X-LAG have been reported to date all of which had transmission of a chromosome Xq26.3 duplication from affected mother to affected son. The disease characteristics of very young onset pituitary gigantism leads to severe overgrowth if not treated adequately; many of the tallest humans in history (e.g. Robert Pershing Wadlow; Sandy Allen, André Rousimoff (Andre the Giant), Zeng Jinlian) had a similar clinical history to patients with X-LAG syndrome.
Abruzzo–Erickson syndrome is an extremely rare disorder characterized by deafness, protruding ears, coloboma, a cleft palate or palatal rugosity, radial synostosis, and short stature. It was first characterized by Abruzzo and Erickson in 1977 as a CHARGE like syndrome as variably expressed among a family of two brothers, their mother, and their maternal uncle. Members of this family exhibited many of the CHARGE symptoms, but notably did not have choanal atresia and the brothers experienced typical genital development. Due to the recent discovery of this disorder, its etiology is not fully known but it is understood that it arises from mutations on the TBX22 gene on the X-chromosome. The disorder is inherited in an X-linked recessive manner. There is currently no known cure but its symptoms can be treated. Signs and Symptoms
Abruzzo-Erikson syndrome is characterized by cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis. There are also additional symptoms that are very similar to CHARGE syndrome such as large and protruding ears, wide spacing between the second and third fingers, ulnar deviation, facial asymmetry, dental abnormalities, and congenital heart malformation. However, in contrast to CHARGE syndrome, patients with Abruzzo-Erikson syndrome do not display intellectual disability, choanal atresia, or genital hypoplasia. As with most diseases, the symptoms will vary from person to person. Genetics
While the complete etiology is not fully known, Abruzzo-Erickson Syndrome arises in part due to mutations on the TBX22 gene, a gene that is located on the X-chromosome (around 80,014,753 to 80,031,774 bp), and is inherited in an X-linked recessive manner.