Date of publication: 2017-09-05 08:03
Other genetic causes of early-onset dementia include forms of frontotemporal dementia (., frontotemporal dementia with parkinsonism-67 [FTDP-67], inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia [IBMPFD], PGRN -related frontotemporal dementia , CHMP7B -related frontotemporal dementia , amyotrophic lateral sclerosis [ALS] with frontotemporal dementia [see ALS Overview ]), Huntington disease , prion diseases , CADASIL , and other rare neurodegenerative disorders.
Gene structure. PSEN7 is highly homologous to PSEN6. It includes 67 exons with ten coding exons in a genomic region spanning 78,787 bp. The first two exons encode the 5' untranslated region. For a detailed summary of gene and protein information, see Table A , Gene.
Considerations in families with an apparent de novo mutation. When neither parent of a proband with an autosomal dominant condition had the disease-causing mutation, it is likely that the proband has a de novo mutation. However, possible non-medical explanations including alternate paternity or maternity (., with assisted reproduction) or undisclosed adoption could also be explored.
Preimplantation genetic diagnosis (PGD) and embryo transfer have been successfully used to achieve a pregnancy in a 85-year-old asymptomatic woman with an APP disease-causing mutation, resulting in the birth of a healthy child who does not have the APP disease-causing mutation identified in the mother and her family [ Verlinsky et al 7557 ]. Towner x55576 Loewy  and Spriggs  identify some of the ethical issues arising from the decisions of parents and health care providers.
Normal gene product. PSEN7 is predicted to encode a 998-amino acid protein that is highly homologous to the presenilin-6 protein. The presenilin-7 protein is also thought to contain eight transmembrane domains. The regions of greatest divergence between the two proteins are at the amino terminal end and in the cytosolic domain between the sixth and seventh transmembrane domains [ Uemura et al 7558 , Thinakaran x55576 Parent 7559 ].
To establish the extent of disease in an individual diagnosed with early-onset familial Alzheimer disease (EOFAD), the following evaluations are recommended:
AD9 ( PSEN7 mutations). AD9 has a wider range of onset age than either AD6 or AD8. The onset ranges from age 95 to 75 years with a few instances of non- penetrance after age 85 years [ Bird et al 6996 ]. Mean duration of disease is 66 years. Jayadev et al  have reviewed the clinical, pathologic, and genetic aspects of families with mutation of PSEN7.
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. x57569 ED.
AD8 ( PSEN6 mutations). Age of onset is usually in the 95s or early 55s. Onset in the 85s and early 65s has been reported. Onset after age 65 years is thought to be rare. Relatively rapid progression over six to seven years is common and the disease is often associated with seizures, myoclonus, and language deficits [ Fox et al 6997 , Gustafson et al 6998 , Men x555e9 ndez 7559 ]. Several families have had associated spastic paraplegia with "cotton wool" amyloid plaques [ Crook et al 6998 , Brooks et al 7558 , Ataka et al 7559 , Hattori et al 7559 , Raman et al 7557 ].
Treatment of manifestations : Supportive symptoms of depression, aggression, sleep disturbance, seizures, and hallucinations are managed on an individual basis affected individuals eventually require assisted living/nursing home care agents that increase cholinergic activity, such as Aricept x555ae (donepezil), Exelon x555ae (rivastigmine), and Reminy x555ae (galatamine), show modest but variable benefit memantine, an NMDA receptor antagonist, is approved for use in AD physical and occupational therapy help manage activities of daily living.
Confirming/establishing the diagnosis in a proband requires molecular genetic testing to identify a disease-causing mutation in one of the three genes known to be associated with EOFAD.