1p36 deletion syndrome is a

congenital A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...

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 chromosome abnormality. Although polygenic disorders ...

characterized by moderate to severe

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 ...

, delayed growth,

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but it is a potential manifestation of many different dis ...

, seizures, limited speech ability, malformations, hearing and vision impairment, and distinct facial features. The symptoms may vary, depending on the exact location of the chromosomal deletion. The condition is caused by a

genetic deletion In genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) (sign: Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is left out during DNA replication. Any number of nucleoti ...

(loss of a segment of DNA) on the outermost band on the short arm (p) of

chromosome 1 Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which a ...

. It is one of the most common deletion syndromes. The syndrome is thought to affect one in every 5,000 to 10,000 births.

Signs and symptoms

There are a number of signs and symptoms characteristic of monosomy 1p36, but no one individual will display all of the possible features. In general, children will exhibit

failure to thrive Failure to thrive (FTT), also known as weight faltering or faltering growth, indicates insufficient weight gain or absence of appropriate physical growth in children. FTT is usually defined in terms of weight, and can be evaluated either by a low ...

and global delays.

Developmental and behavioral

Most young children with 1p36 deletion syndrome have delayed development of speech and motor skills. Speech is severely affected, with many children learning only a few words or having no speech at all. Behavioral problems are also common, and include temper outbursts, banging or throwing objects, striking people, screaming episodes, and self-injurious behavior (wrist biting, head striking/banging). A significant proportion of affected people are on the

autism spectrum Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing d ...

, and many exhibit

stereotypy A stereotypy (, ) is a repetitive or ritualistic movement, posture, or utterance. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing, crossing and uncrossing of legs, and marching in place. They are foun ...

Neurologic

Most people with 1p36 deletion syndrome have some structural abnormality of the brain, and approximately half have

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

or other seizures. Almost all children exhibit some degree of

. Common structural brain abnormalities include

agenesis of the corpus callosum Agenesis of the corpus callosum (ACC) is a rare birth defect in which there is a complete or partial absence of the corpus callosum. It occurs when the development of the corpus callosum, the band of white matter connecting the two hemispheres ...

, cerebral cortical atrophy, gait abnormalities, and

ventriculomegaly Ventriculomegaly is a brain condition that mainly occurs in the fetus when the lateral ventricles become dilated. The most common definition uses a width of the atrium of the lateral ventricle of greater than 10 mm. This occurs in around 1 ...

Dysphagia Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or l ...

, esophageal reflux, and other feeding difficulties are also common.

Vision

The most common visual abnormalities associated with 1p36 deletion syndrome include

farsightedness Far-sightedness, also known as long-sightedness, hypermetropia, and hyperopia, is a condition of the eye where distant objects are seen clearly but near objects appear blurred. This blur is due to incoming light being focused behind, instead o ...

(hypermetropia),

myopia Myopia, also known as near-sightedness and short-sightedness, is an eye condition where light from distant objects focuses in front of, instead of on, the retina. As a result, distant objects appear blurry, while close objects appear normal. ...

(nearsightedness), and

strabismus Strabismus is an eye disorder in which the eyes do not properly align with each other when looking at an object. The eye that is pointed at an object can alternate. The condition may be present occasionally or constantly. If present during a ...

(cross-eyes). Less common but still recognized are

blepharophimosis Blepharophimosis is a congenital anomaly in which the eyelids are underdeveloped such that they cannot open as far as usual and permanently cover part of the eyes. Both the vertical and horizontal palpebral fissures (eyelid openings) are shortene ...

cataract A cataract is a cloudy area in the lens (anatomy), lens of the eye that leads to a visual impairment, decrease in vision of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or ...

s, ocular albinism, optic atrophy, optic disk pallor, and optic nerve coloboma.

Distinct facial features

The facial features of 1p36 deletion syndrome have been considered to be characteristic, although few patients have been diagnosed solely on the basis of facial appearance. These features may include

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 ...

(small head), which may be combined with

brachycephaly Brachycephaly (derived from the Ancient Greek '' βραχύς'', 'short' and '' κεφαλή'', 'head') is the shape of a skull shorter than average in its species. It is perceived as a cosmetically desirable trait in some domesticated dog and ...

(short head); small, deep-set eyes; straight eyebrows; epicanthal folds; a broad, flat nose and nasal bridge; underdevelopment of the midface (midface hypoplasia); a long philtrum; pointed chin; and abnormally shaped, rotated, low-set ears. Infants may have a large

anterior fontanelle The anterior fontanelle (bregmatic fontanelle, frontal fontanelle) is the largest fontanelle, and is placed at the junction of the sagittal suture, coronal suture, and frontal suture; it is lozenge-shaped, and measures about 4 cm in its ant ...

, or the anterior fontanelle may close late.

Other congenital defects

Skeletal

Short feet, brachydactyly (short fingers), and camptodactyly (permanent flexion of a finger), fifth finger clinodactyly (abnormal curvature) and other skeletal anomalies are sometimes found in conjunction with 1p36 deletion.

Heart

These patients may have congenital heart defects ranging from cardiac septal defects to valvular anomalies and tetralogy of Fallot. In particular, some of the patients may have LV noncompaction a form of dilated cardiomyopathy. This form of LV noncompaction cardiomyopathy is thought to be related to the deletion of the gene CASZ1, this gene in mice leads to ventricular noncompaction.

Genitourinary and kidneys

Genetics

1p36 deletion syndrome is caused by the deletion of the most

distal Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position provi ...

light band of the short arm of

The breakpoints for 1p36 deletion syndrome have been variable and are most commonly found from 1p36.13 to 1p36.33. 40 percent of all breakpoints occur 3 to 5 million

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

s from the

telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see #Sequences, Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In ...

. The size of the deletion ranges from approximately 1.5 million base pairs to greater than 10 million. Most deletions in chromosome 1p36 are

de novo mutation A de novo mutation (DNM) is any mutation or alteration in the genome of an individual organism (human, animal, plant, microbe, etc.) that was not inherited from its parents. This type of mutation spontaneously occurs during the process of DNA repl ...

s. 20% of patients with 1p36 deletion syndrome inherit the disease from one parent who carries a balanced or symmetrical translocation.

Diagnosis

1p36 deletion syndrome is usually suspected based on the signs and symptoms and confirmed by

fluorescence in situ hybridization Fluorescence ''in situ'' hybridization (FISH) is a molecular cytogenetic technique that uses fluorescent probes that bind to only particular parts of a nucleic acid sequence with a high degree of sequence complementarity. It was developed by ...

(FISH). Chromosomal microarray or

karyotype 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 ...

analysis may also be used to diagnose 1p36 deletion.

Treatment

There is no cure for 1p36 deletion syndrome, and treatment is focused on relieving symptoms of the disease. Of particular importance are appropriate medication for endocrine and neurologic manifestations, such as anti-seizure medications. Feeding difficulties can be managed with specialized assistive devices or with a gastrostomy (feeding) tube.

Epidemiology

1p36 deletion syndrome is the most common terminal deletion syndrome in humans. It occurs in between 1 in 5000 and 1 in 10000 live births. Only 100 cases have been reported between 1981 and 2015. The Genetic and Rare Disease Information Center at the

National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

reports "fewer than 200,000 people in the United States are living with this disorder."

References

External links

{{Medical resources , ICD11 = , ICD10 = , ICD10CM = , ICD9 = , ICDO = , OMIM = 607872 , OMIM_mult = {{OMIM, 616975 , MeshID = C535362 , DiseasesDB = 34535 , SNOMED CT = 699306003 , Curlie = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , PatientUK = , NCI = , GeneReviewsNBK = , GeneReviewsName = , NORD = , GARDNum = 6082 , GARDName = 1p36 deletion syndrome , RP = 56295 , AO = , WO = , OrthoInfo = , Orphanet = 1606 , Scholia = Q3297103 , OB = Autosomal monosomies and deletions Syndromes with intellectual disability Syndromes with seizures Syndromes with craniofacial abnormalities Genetic anomalies Syndromes affecting the eye Syndromes with microcephaly Syndromes affecting the heart Syndromes affecting hearing