Monosomy 9p (also known as Alfi's Syndrome, 9p Minus or simply 9P-) is a rare chromosomal disorder in which some

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

is missing or has been deleted on the short arm region, "p", of one copy of

chromosome 9 Chromosome 9 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome, as they normally do with all chromosomes. Chromosome 9 spans about 138 million base pairs of nucleic acids (the building blocks of DN ...

(9p22.2-p23). This deletion either happens

de novo De novo (Latin, , used in English to mean 'from the beginning', 'anew') may refer to: Science and computers * ''De novo'' mutation, a new germline mutation not inherited from either parent * ''De novo'' protein design, the creation of a protei ...

or as a result of a parent having the

chromosome abnormality A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where the ...

. This rare chromosomal abnormality is often diagnosed after birth when developmental delay, irregular

facial feature The face is the front of the head that features the eyes, nose and mouth, and through which animals express many of their emotions. The face is crucial for human identity, and damage such as scarring or developmental deformities may affect ...

s, structural irregularities within the heart, and genital defects are observed. Treatments for this syndrome usually focus on fixing the

malformations A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities Disability is the experience of any condition that makes it more difficult for a person to do certain act ...

that are commonly associated with it. The cause of the syndrome was first discovered by Dr. Omar Alfi in 1973, when an analysis of the chromosomes of three infants with similar clinical abnormalities revealed that they all had a partial deletion of the short arm of Chromosome 9. Symptoms includ
micro genitalia

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

with

microcephaly Microcephaly (from Neo-Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it m ...

and

dysmorphic feature A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, genetic syndrome or birth defect. Dysmorphology is the study of dysm ...

Signs and symptoms

Psychomotor development delays

Psychomotor developmental delays are delays in the emergence of the psychomotor skills that naturally develop from birth through

adolescence Adolescence () is a transitional stage of human Developmental biology, physical and psychological Human development (biology), development that generally occurs during the period from puberty to adulthood (typically corresponding to the age o ...

, including

cognitive Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

, emotional,

motor An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy. Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power gene ...

, language, and

social skills A social skill is any competence facilitating interaction and communication with others where social rules and relations are created, communicated, and changed in verbal and nonverbal ways. The process of learning these skills is called socia ...

. The severity of these delays can vary.

Facial dysmorphism

Facial dysmorphism A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, Genetics, genetic syndrome or birth defect. Dysmorphology is the stud ...

s are abnormalities in facial structure, including a sloping forehead, a prominent protruding forehead,

hemifacial microsomia Hemifacial microsomia (HFM) is a congenital disorder that affects the development of the lower half of the face, most commonly the ears, the mouth and the mandible. It usually occurs on one side of the face, but both sides are sometimes affected. ...

(in which one side of the face is underdeveloped), and otocephaly (an absence of the mandible and a fusion of the ears under the chin).

Malformation of limbs

Congenital limb defects are the result of altered development of a

fetus A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic development, embryonic stage, the fetal stage of development takes place. Pren ...

's upper or lower limb, including absence of the limb, a failure of portions of the limb (commonly fingers and toes) to separate, duplication of digits, overgrowth, or undergrowth.

Genetics

Inheritance pattern

The

inheritance Inheritance is the practice of receiving private property, titles, debts, entitlements, privileges, rights, and obligations upon the death of an individual. The rules of inheritance differ among societies and have changed over time. Offi ...

pattern for monosomy 9p is inherited in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

inheritance pattern. This means that a single copy of the deletion is sufficient to cause the disease.

Mutation

The

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, ...

, which occurs in the form of a deletion of the short arm of chromosome 9, causes the cell to not express the gene products normally controlled by the

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s within the chromosome 9 deletion.

Genes involved

The 9p deletion causes a loss of genes that would normally be there. The signs, symptoms and severity of the condition depend on the specific genes that are lost. Most of the genes involved are associated with the development of tissues. There are many possible genes that can be deleted, but two particular genes,

DMRT1 Doublesex and mab-3 related transcription factor 1, also known as DMRT1, is a protein which in humans is encoded by the ''DMRT1'' gene. Function DMRT1 is a dose sensitive transcription factor protein that regulates Sertoli cells and germ cell ...

and DMRT2, are known to be involved. When DMRT1 and DMRT2 are deleted,

genital A sex organ, also known as a reproductive organ, is a part of an organism that is involved in sexual reproduction. Sex organs constitute the primary sex characteristics of an organism. Sex organs are responsible for producing and transporting ...

malformations and

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

are evident, but the direct mechanisms for these problems remain undefined.

Location

Geneticist A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic process ...

s originally had the syndrome narrowed down to the short arm region of chromosome 9. Now, the location of the deletion has recently been narrowed to 9p22.2-p23.

Diagnosis

Diagnoses can occur at any age. Most of the time chromosome 9p deletion syndrome is diagnosed after birth by the detection of symptoms via clinical evaluation. Common methods used to detect monosomy 9p after birth include the use of a

stethoscope The stethoscope is a medicine, medical device for auscultation, or listening to internal sounds of an animal or human body. It typically has a small disc-shaped resonator that is placed against the skin, with either one or two tubes connected t ...

X-ray An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...

, and EKG. Monosomy 9p is also diagnosed before birth by

ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...

amniocentesis Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ...

, and

chorionic villus sampling Chorionic villus sampling (CVS), sometimes called "chorionic ''villous'' sampling" (as "villous" is the adjectival form of the word "villus"), is a form of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus. It en ...

(CVS). Ultrasound can hint at the malformations of the face, limbs, and heart, while

and CVS both use fluid and tissue to perform chromosomal studies to identify chromosomal abnormalities. Finally,

karyotyping A karyotype is the general appearance of the complete set of chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is discerned by de ...

, a procedure used to examine a patient's chromosomes, can be used to diagnose monosomy 9p both before birth and after birth.

Management

Treatment of monosomy 9p focuses mainly on fixing the malformations. For example, to fix facial malformations, physicians can perform facial surgery to repair the facial malformations. This can open airways for the infant or patient, especially the nose-to-throat pathway. Similarly, to fix heart malformations, physicians can recommend surgery or medication to improve the efficiency of the pumping of the heart. Lastly

remedial education Remedial education (also known as developmental education, basic skills education, compensatory education, preparatory education, and academic upgrading) is assigned to assist students in order to achieve expected competencies in core academic sk ...

speech therapy Speech is the use of the human voice as a medium for language. Spoken language combines vowel and consonant sounds to form units of meaning like words, which belong to a language's lexicon. There are many different intentional speech acts, suc ...

, and

physical therapy Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

can be used to improve the developmental delay associated with the syndrome.

Epidemiology

Monosomy 9p occurs 1 in 50,000 births. Half of the cases occur sporadically, while the other half of the cases result from parent

translocations In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes "balanced" and "unbalanced" translocation, with three main types: "reciprocal", "nonreciprocal" and "Robertsonian" transloc ...

or the parent having deletion as well.

References

External links

{{Chromosomal abnormalities Autosomal monosomies and deletions