1p36 deletion syndrome

1p36 deletion syndrome is a congenital genetic disorder characterized by moderate to severe intellectual disability, delayed growth, hypotonia, 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.[1]

1p36 deletion syndrome
Other names	Monosomy 1p36
A toddler showing facial symptoms of the syndrome.

The condition is caused by a genetic deletion (loss of a segment of DNA) on the outermost band on the short arm (p) of chromosome 1. It is one of the most common deletion syndromes. It is estimated that the syndrome occurs in 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 and global delays.[2]

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, and many exhibit stereotypy.[2][3]

Neurologic

Most people with 1p36 deletion syndrome have some structural abnormality of the brain, and approximately half have epilepsy or other seizures.[3][2] Almost all children exhibit some degree of hypotonia.[4] Common structural brain abnormalities include agenesis of the corpus callosum, cerebral cortical atrophy, gait abnormalities, and ventriculomegaly. Dysphagia, esophageal reflux, and other feeding difficulties are also common.[2]

Vision

The most common visual abnormalities associated with 1p36 deletion syndrome include farsightedness (hypermetropia), myopia (nearsightedness), and strabismus (cross-eyes). Less common but still recognized are blepharophimosis, cataracts, ocular albinism, optic atrophy, optic disk pallor, and optic nerve coloboma.[2]

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 (small head), which may be combined with brachycephaly (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.[3] Infants may have a large anterior fontanelle, or the anterior fontanelle may close late.[5]

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.[4]

Heart

Genitourinary and kidneys

Genetics

1p36 deletion syndrome is caused by the deletion of the most distal light band of the short arm of chromosome 1.[4]

Human chromosome 1

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 pairs from the telomere. 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 mutations. 20% of patients with 1p36 deletion syndrome inherit the disease from one parent who carries a balanced or symmetrical translocation.[3]

Diagnosis

1p36 deletion syndrome is usually suspected based on the signs and symptoms and confirmed by fluorescence in situ hybridization (FISH).[6] Chromosomal microarray or karyotype analysis may also be used to diagnose 1p36 deletion.[4]

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.[2]

Epidemiology

1p36 deletion syndrome is the most common terminal deletion syndrome in humans.[5] It occurs in between 1 in 5000 and 1 in 10000 live births.[3]

References

1. "Chromosome 1, 1p36 deletion syndrome". WrongDiagnosis. Retrieved 2009-05-25.
2. "Chromosome 1p36 deletion syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 19 September 2018.
3. "1p36 deletion syndrome". Genetics Home Reference. NIH.
4. Battaglia, Agatino (June 6, 2013), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "1p36 Deletion Syndrome", GeneReviews®, University of Washington, Seattle, PMID 20301370, retrieved 2019-02-20
5. "OMIM Entry - # 607872 - CHROMOSOME 1p36 DELETION SYNDROME". www.omim.org. Retrieved 19 September 2018.
6. "Chromosome 1p36 deletion syndrome". Genetics Testing Reference. Retrieved 2019-02-20.

Classification	D OMIM: 607872 MeSH: C535362 C535362, C535362 DiseasesDB: 34535