MORM syndrome is an

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

congenital disorder A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

characterized by

mental retardation Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signific ...

, truncal obesity, retinal dystrophy, and

micropenis Micropenis is an unusually small penis. A common criterion is a dorsal (measured on top) penile length of at least 2.5 standard deviations smaller than the mean human penis size (stretched penile length less than 9.3 cm (3.67 in) in adults). ...

". The disorder shares similar characteristics with

Bardet–Biedl syndrome Bardet–Biedl syndrome (BBS) is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized by rod/cone dystrophy, polydactyly, central obesity, hypogonadism, and kidney dysfunction in som ...

and

Cohen syndrome Cohen syndrome (also known as Pepper syndrome or Cervenka syndrome) is a very rare autosomal recessive genetic disorder with varied expression, characterised by obesity, intellectual disability, distinct craniofacial abnormalities and potential ocu ...

, both of which are autosomal recessive genetic disorders. MORM syndrome can be distinguished from the above disorders because symptoms appear at a young age. The disorder is not dependent on sex of the offspring, both male and female offspring are equally likely to inherit the disorder. The syndrome is caused by a mutation in the

INPP5E 72 kDa inositol polyphosphate 5-phosphatase, also known as phosphatidylinositol-4,5-bisphosphate 5-phosphatase or Pharbin, is an enzyme that in humans is encoded by the ''INPP5E'' gene. Function INPP5E is a phosphatidylinositol (3,4,5)-trispho ...

gene which can be located on chromosome 9 in humans. Further mapping resulted in the identification of a MORM syndrome locus on chromosome 9q34.3 between the genetic markers D9S158 and D9S905.

Presentation

For individuals with MORM syndrome, symptoms do not appear until about one year of age. From conception to birth, individuals with MORM syndrome appear asymptotic, with no abnormal characteristics. Vision is negatively affected within the first year of life, particularly night vision. Individuals with MORM syndrome experience decreased

visual acuity Visual acuity (VA) commonly refers to the clarity of vision, but technically rates an examinee's ability to recognize small details with precision. Visual acuity is dependent on optical and neural factors, i.e. (1) the sharpness of the retinal ...

, meaning their ability to see distinct sharp lines decreases. Vision quality continues to deteriorate until age three. Any further reduction in vision acuity is not observed until the individual is between the ages thirty to forty. Delayed

sentence processing Sentence processing takes place whenever a reader or listener processes a language utterance, either in isolation or in the context of a conversation or a text. Many studies of the human language comprehension process have focused on reading of s ...

and

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

is associated with individuals with MORM syndrome, primarily observed at age four. Individuals continue to develop and grow until they are five to twelve years old. During this age bracket, truncal obesity can develop, characterized by the buildup of fat around one's trunk or torso as opposed to the person's extremities. Males enter puberty at around age twelve and develop normally, except for their penis, which will remain at the prepubescent size, resulting in a

. Both the life span and fertility of individuals with MORM syndrome is unclear .

Genetic

MORM syndrome is associated with the gene INPP5E. INPP5E is a gene whose function is not well understood. It is hypothesized to play a role in primary cilia stability. A

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

in the INPP5E gene, on chromosome 9q34, is the cause for MORM syndrome. The mutation causes a homozygous transition in the last

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

of the INPP5E gene. This transition results in the

DNA bases Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic b ...

changing from a cytosine residue to a thymine residue. The resulting protein will then have an altered amino acid sequence. In unaffected individuals this specific

codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...

(region of DNA bases) is supposed to code for the amino acid glutamine. In cases of MORM syndrome this codon codes for a termination sequence, which prematurely stops the production of the protein. In unaffected individuals the protein is evenly disbursed throughout the

cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...

axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axonem ...

, which stabilizes the cilia, which are antenna like structures which protrude from the extracellular surface of the cell. They play an important role in extracellular signalling/communication between cells and their environment. When the INPP5E gene is mutated, the protein is damaged and is unable to spread out along the cilia axoneme or interact with other stabilizing proteins. This inability to stabilize one's cilia axoneme results in MORM syndrome. The exact mechanism as to how the mutation in the INPP5E gene causes cilia instability is still not well understood.

Diagnosis

MORM syndrome is a

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

obtained through

inheritance Inheritance is the practice of receiving private property, Title (property), titles, debts, entitlements, Privilege (law), privileges, rights, and Law of obligations, obligations upon the death of an individual. The rules of inheritance differ ...

. The main method for testing individuals showing symptoms of MORM syndrome is

sequence analysis In bioinformatics, sequence analysis is the process of subjecting a DNA, RNA or peptide sequence to any of a wide range of analytical methods to understand its features, function, structure, or evolution. Methodologies used include sequence alignm ...

of the entire

coding region The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to no ...

. When performing a sequence analysis of the entire coding region the gene INPP5E is targeted. Sequence analysis is the

biotechnological Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used by ...

process in which the structure and sequence of DNA,

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

, or

protein sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthesi ...

is determined through the use of technology. This sequence can be analyzed to determine

s or abnormalities in that particular region. When testing for MORM syndrome, sequence analysis of the region of the genome which contains the gene INPP5E is targeted and examined to look for mutations.

Management

References

External links

{{Medicine, state=collapsed Autosomal recessive disorders Congenital disorders Rare syndromes