• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

1p36 Deletion Syndrome

Synonym: Monosomy 1p36 Syndrome
, MD
Stella Maris Clinical Research Institute for Child and Adolescent Neurology and Psychiatry
Calambrone (Pisa), Italy

Initial Posting: ; Last Update: June 6, 2013.

Summary

Disease characteristics. 1p36 deletion syndrome is characterized by typical craniofacial features consisting of straight eyebrows, deeply set eyes, midface retrusion, wide and depressed nasal bridge, long philtrum, pointed chin, large, late-closing anterior fontanel (77%), microbrachycephaly (65%), epicanthal folds (50%), and posteriorly rotated, low-set, abnormal ears. Other characteristic findings include brachy/camptodactyly and short feet. Developmental delay/intellectual disability of variable degree are present in all, and hypotonia in 95%. Seizures occur in 44%-58% of affected individuals. Other findings include structural brain abnormalities (88%), congenital heart defects (71%), eye/vision problems (52%), hearing loss (47%), skeletal anomalies (41%), abnormalities of the external genitalia (25%), and renal abnormalities (22%).

Diagnosis/testing. The diagnosis of 1p36 deletion syndrome is suggested by clinical findings and confirmed by detection of a deletion of the most distal band of the short arm of chromosome 1 (1p36). Conventional G-banded cytogenetic analysis, FISH, or chromosomal microarray (CMA) can all be used to detect deletions; however, the complexity of some deletions may be detected only by CMA.

Management. Treatment of manifestations: Rehabilitation/educational program with attention to speech/communication, use of sign language, motor development, cognition, and social skills; ACTH for infantile spasms; routine antiepileptic drugs (AEDs) for other seizure types; special feeding techniques and/or devices including gastrostomy tube for feeding difficulties; standard pharmacotherapy for non-compaction cardiomyopathy; standard care for eye/vision problems, skeletal anomalies, hearing loss, hypothyroidism, and renal abnormalities.

Surveillance: Systematic follow-up for adjustment of rehabilitation/education and medical treatment as needs change over time.

Genetic counseling. 1p36 deletion syndrome is caused by deletion of the 1p36 chromosome region by one of several genetic mechanisms. Approximately 52% of individuals with 1p36 deletion syndrome have a de novo terminal 1p36 deletion, approximately 29% have an interstitial deletion, approximately 12% have more complex chromosome rearrangements that may include more than one 1p36 deletion or a 1p36 deletion with a 1p36 duplication, and approximately 7% have a derivative chromosome 1 (in which the 1p telomeric region is replaced by another chromosome end). Risks to family members depend on the mechanism of origin of the deletion. Prenatal testing is possible for families who have had a child with 1p36 deletion syndrome or a family in which one parent is a known carrier of a chromosome rearrangement involving 1p36.

Diagnosis

Clinical Diagnosis

The diagnosis of 1p36 deletion syndrome is suggested by the characteristic facial appearance, hypotonia, psychomotor retardation, and poor or absent speech and is confirmed by detection of a deletion of the most distal band of the short arm of chromosome 1 (1p36).

Typical facial features. The facial appearance of individuals with 1p36 deletion syndrome remains easily recognizable over time [Battaglia et al 2008], representing a hallmark of the condition [Battaglia 2005] (see Figure 1). Facial features include straight eyebrows, deeply set eyes, midface retrusion, wide and depressed nasal bridge, long philtrum, and pointed chin. Other craniofacial features are microcephaly, brachycephaly, epicanthal folds, large (>3 cm at birth) and late-closing anterior fontanel, and posteriorly rotated, low-set, abnormally formed ears [Shapira et al 1997, Heilstedt et al 2003b, Battaglia et al 2008].

Figure 1

Figure

Figure 1. Two unrelated children showing microbrachycephaly, straight eyebrows, deeply set eyes, wide and depressed nasal bridge, midface retrusion, elongated philtrum, pointed chin, and hypotonic face

A. Girl age 9.5 years

B. (more...)

Developmental delay/intellectual disability of variable degree is present in all. Generalized hypotonia is observed in 95% of individuals [Battaglia et al 2008].

Testing

Cytogenetic analysis. The four classes of rearrangements identified in individuals with monosomy 1p36 are shown in Table 1 [Heilstedt et al 2003b, Gajecka et al 2007]:

  • An apparently "pure" terminal deletion
  • Interstitial deletion
  • More complex rearrangements including more than one deletion or deletions with duplications, triplications, insertions, and/or inversions
  • Derivative chromosome 1 resulting from an unbalanced translocation

Note: (1) No common breakpoint or deletion size is present in individuals with monosomy 1p36. (2) Determining whether a cytogenetically visible deletion is a true terminal deletion or a more complex rearrangement may be accomplished using specialized molecular cytogenetic techniques (see Molecular Genetic Testing).

Table 1. Chromosome Abnormalities Seen in 1p36 Deletion Syndrome

Chromosome Abnormality
Terminal deletionInterstitial deletionComplex rearrangement 1Derivative chromosome 2
Chromosome diagramImage del1p36FigA.jpgImage del1p36FigB.jpgImage del1p36FigC.jpgImage del1p36FigD.jpg
Proportion of 1p36 deletion syndrome 52%29%12%7%

Heilstedt et al [2003b], Gajecka et al [2007]

1. Including more than one deletion or deletions with duplications, triplications, insertions, and/or inversions affecting chromosome 1p36

2. The 1p telomeric region is replaced by another chromosome end.

Molecular Genetic Testing

Genes. Deletion of genes in the 1p36 critical region is the only known cause of 1p36 deletion syndrome.

Clinical testing

Table 2. Summary of Cytogenetic and Molecular Genetic Testing Used in 1p36 Deletion Syndrome

Test Method 1 Mutations DetectedMutation Detection Frequency by Test Method 2
Cytogenetic analysis 3 >5-Mb deletion of 1p36 4 ~25%
FISH 5>100-kb deletion of 1p36 4>95%
Deletion/duplication analysis by CMA 6, 7>95%

Mb = 106 DNA base pairs; kb = 103 DNA base pairs

1. MLPA is not a recommended method of detection of deletions of these sizes.

2. The ability of the test method used to detect a mutation that is present in the indicated gene

3. Conventional G-banded cytogenetic studies (routine and high-resolution)

4. Deletions greater than 5 Mb occur at approximately the same frequency as deletions smaller than 5 Mb.

5. FISH using at least two subtelomeric region-specific probes (Vysis 1p subtel probe, Vysis p58 probe; D1Z2 Oncor probe or CEB108/T7) can identify parental rearrangements and may detect terminal and interstitial deletions and derivative chromosomes.

6. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

7. Terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes can potentially be detected by CMA.

Testing Strategy

To confirm/establish the diagnosis in a proband. It is appropriate to test any individual suspected of having 1p36 deletion syndrome as follows:

  • Conventional cytogenetic studies to detect large deletions (i.e., >5 Mb) and more complex cytogenetic rearrangements (unbalanced chromosome translocations)
  • FISH with at least two subtelomeric region-specific probes (Vysis 1p subtel probe, Vysis p58 probe; D1Z2 Oncor probe or CEB108/T7) to detect unbalanced translocations and to identify parental chromosome rearrangements
  • Deletion/duplication analysis by CMA to detect smaller deletions (i.e., <5 Mb) or interstitial deletions or complex rearrangements

Notes: (1) Subtelomere FISH detects the presence/absence of the two probes used; thus, FISH (a) cannot detect an interstitial deletion proximal to the probes; (b) cannot distinguish between a "true" terminal deletion and a more complex rearrangement; or (c) cannot define the extent of the deletion. However, CMA has the potential to do all three. (2) MLPA, a type of deletion/duplication analysis, is not a recommended method for detection of deletions of these sizes.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies requires prior confirmation of the diagnosis of 1p36 deletion syndrome in the proband and/or balanced status of a parent.

Clinical Description

Natural History

The frequencies of the major clinical findings associated with 1p36 deletion syndrome are summarized in Table 3.

Table 3. Frequency of Major Clinical Findings in 1p36 Deletion Syndrome

FindingsFrequency
  • Distinctive facial features (see Clinical Diagnosis)
  • Intellectual disability
  • Poor/absent speech
  • Hypotonia
  • Brachycamptodactyly
  • Short feet
  • Brain abnormalities
>75%
  • Congenital heart defects
  • Eye/vision problems including visual inattention
  • Seizures
50%-75%
  • Skeletal anomalies
  • Sensorineural deafness
  • Gastrointestinal anomalies
  • Abnormalities of the external genitalia
  • Behavior disorders
25%-50%
  • Non-compaction cardiomyopathy
  • Renal anomalies
  • Anal anomalies
  • Hypothyroidism
<25%

Intellectual disability. Developmental delay and intellectual disability are hallmarks of the syndrome. Battaglia et al [2008] found that 25% of affected individuals can walk alone, with a broad-based gait, by age two to seven years. Approximately 90% have severe to profound intellectual disability, whereas 10% have mild to moderate cognitive impairment. Expressive language is absent in 75% and limited to a few isolated words or at the level of first word associations in the remainder. Comprehension seems to be limited to a specific context. Intention to communicate, limited in early years, tends to improve over time, with extension of the gesture repertoire.

Behavior disorders, present in 50%, include poor social interaction, temper tantrums, self-biting of hands and wrists, a number of stereotypies, and, less frequently, hyperphagia.

Central nervous system defects, present in 88% of affected individuals, mainly include dilatation of the lateral ventricles and subarachnoid spaces; cortical atrophy; diffuse brain atrophy; and hypoplasia, thinning, and total or partial absence of the corpus callosum. Other reported anomalies are delay in myelination, multifocal hyperintensity areas in the white matter [Battaglia et al 2008], periventricular nodular heterotopia [Neal et al 2006, Descartes et al 2011], and polymicrogyria [Dobyns et al 2008].

Seizures occur in 44% to 58% of individuals with 1p36 deletion syndrome [Heilstedt et al 2001, Heilstedt et al 2003b, Bahi-Buisson et al 2008, Battaglia et al 2008]. Age at onset ranges from four days to two years, eight months. First seizures are either generalized (tonic, tonic-clonic, clonic, myoclonic) or partial (simple or complex). Almost 20% of all persons with the disorder have infantile spasms associated with hypsarrhythmia on EEG. Infantile spasms may either be the presenting seizure type or may follow other seizure types. Most seizure types are well controlled by standard pharmacotherapy. However, in one series [Bahi-Buisson et al 2008] nearly one third of persons developed drug-resistant epilepsy.

Of note, epileptic apneas can also occur in some children [Kanabar et al 2012]; and early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome) has also been reported in an individual [Paciorkowski et al 2011].

A variety of EEG abnormalities are present in nearly all affected individuals [Heilstedt et al 2001, Bahi-Buisson et al 2008, Battaglia et al 2008].

Feeding difficulties may be caused by hypotonia and/or oral facial clefts with related difficulty in sucking, poorly coordinated swallow with consequent aspiration, and/or gastroesophageal reflux and vomiting. Mild to severe oropharyngeal dysphagia has been observed on swallow studies in 72% of individuals [Heilstedt et al 2003b].

Congenital heart defects are noted in 43% to 71% of individuals. Structural heart defects reported are (in order of frequency) atrial and ventricular septal defects, valvular anomalies, patent ductus arteriousus, tetralogy of Fallot, coarctation of the aorta, infundibular stenosis of the right ventricle, and Ebstein anomaly [Heilstedt et al 2003b, Battaglia et al 2008]. Twenty-seven percent had a history of cardiomyopathy in infancy and childhood. Cardiomyopathy was of the non-compaction type in 23% and tended to improve over time [Battaglia et al 2008].

Opthalmologic abnormalities. Strabismus, nystagmus, refractive errors, and visual inattention are the most common ophthalmic manifestations of 1p36 deletion syndrome [Heilstedt et al 2003b, Battaglia et al 2008]. Cataract, retinal albinism, and optic nerve coloboma have occasionally been observed [Battaglia et al 2008].

Skeletal anomalies found in 40% of individuals with 1p36 deletion syndrome [Battaglia et al 2008] include delayed bone age, scoliosis, rib anomalies, and lower-limb asymmetry.

Hearing loss, mostly of the sensorineural type, can be detected in 47% to 82% of individuals with 1p36 deletion syndrome [Heilstedt et al 2003b, Battaglia et al 2008].

Genitourinary malformations can be seen in 22% of affected individuals and include unilateral renal pelvis with hydronephrosis of the upper pole, kidney ectopia with right kidney cyst, and unilateral pelvic ectasia [Battaglia et al 2008].

Cryptorchidism, hypospadias, scrotal hypoplasia, and micropenis are seen in a minority of males [Battaglia et al 2008].

Small labia minora and small clitoris, labia majora hypertrophy, and uterine hypoplasia have been reported in females [Battaglia et al 2008].

Hypothyroidism has been reported in 15% to 20% of persons of varied ages with deletion 1p36 syndrome in whom TSH and T4 levels were studied [Heilstedt et al 2003b, Battaglia et al 2008].

Other. Other abnormalities reported in a few individuals with 1p36 deletion syndrome include the following:

Genotype-Phenotype Correlations

To explain the phenotypic variability of 1p36 deletion syndrome, investigators have searched for correlations between size of the 1p deletion and severity of clinical manifestations.

Wu et al [1999] and Heilstedt et al [2003b] suggested a complete genotype-phenotype correlation, identifying the critical regions for certain features and considering 1p36 deletion syndrome as a contiguous gene deletion syndrome. However, Gajecka et al [2007] found no correlation between deletion size and number of observed clinical features in a large cohort; even individuals with small (<3 Mb) deletions of 1p36 presented with most of the features commonly associated with the syndrome.

Redon et al [2005] hypothesized that the features associated with 1p36 deletion syndrome may result from a position effect rather than a contiguous gene deletion.

Prevalence

The prevalence of 1p36 deletion syndrome is estimated at between 1:5,000 and 1:10,000 births, with a 2:1 female to male ratio [Shapira et al 1997, Slavotinek et al 1999, Heilstedt et al 2003a, Battaglia et al 2008].

Differential Diagnosis

The clinical phenotype and the facial gestalt of 1p36 deletion syndrome are characteristic. However, some individuals may be misdiagnosed because of features that overlap with the following disorders:

  • Rett syndrome is an X-linked dominant disorder that in girls is characterized by normal birth and apparently normal psychomotor development during the first six to 18 months of life followed by a short period of developmental stagnation and then by rapid regression in language and motor skills. The hallmark of the disease is the loss of purposeful hand use and its replacement with repetitive stereotyped hand movements. Autistic features, panic-like attacks, bruxism, episodic apnea and/or hyperpnea, gait ataxia and apraxia, tremors, and acquired microcephaly also occur. The disease becomes relatively stable, but girls are likely to develop dystonia and foot and hand deformities as they grow older. Seizures occur in 50% of females with Rett syndrome; generalized tonic-clonic seizures and partial complex seizures are the most common. The incidence of sudden, unexplained death is increased. Males with a 46,XY karyotype may have such severe neonatal encephalopathy that they die before their second year. The diagnosis rests on clinical diagnostic criteria established for the classic syndrome and/or molecular testing of MECP2.
  • Angelman syndrome (AS) is characterized by severe developmental delay/intellectual disability, severe speech impairment, gait ataxia and/or tremulousness of the limbs, and a unique behavior with an inappropriate happy demeanor that includes frequent laughing, smiling, and excitability. Microcephaly and seizures are common. The diagnosis rests on a combination of clinical features and molecular genetic testing and/or cytogenetic analysis. Consensus clinical diagnostic criteria for AS have been developed. Analysis of parent-specific DNA methylation imprints in the 15q11.2-q13 chromosome region detects approximately 78% of individuals with AS, including those with a deletion, uniparental disomy, or an imprinting defect; fewer than 1% of individuals have a cytogenetically visible chromosome rearrangement (i.e., translocation or inversion). UBE3A sequence analysis detects mutations in an additional approximately 11% of individuals. Accordingly, molecular genetic testing (methylation analysis and UBE3A sequence analysis) identifies alterations in approximately 90% of individuals. The remaining 10% of individuals with classic phenotypic features of AS have a presently unidentified genetic mechanism and thus are not amenable to diagnostic testing.
  • Prader-Willi syndrome (PWS) is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity (unless it is externally controlled). All individuals have some degree of cognitive impairment, with delay in motor milestones and language development. A specific behavior phenotype with temper tantrums, stubbornness, rigidity, stealing, lying, manipulative behavior, and obsessive-compulsive characteristics is common. Hypogonadism, present in both males and females, manifests as genital hypoplasia, incomplete pubertal development, and, in most, infertility. Short stature with small hands and feet is common; characteristic facial features, strabismus, and scoliosis are often present, and non-insulin-dependent diabetes mellitus often occurs in obese individuals. Consensus clinical diagnostic criteria have been developed, but the mainstay of diagnosis is DNA-based methylation testing to detect abnormal parent-specific imprinting within the Prader-Willi critical region (PWCR) on chromosome 15. This testing determines whether the region is maternally inherited only (the paternally contributed region is absent) and detects more than 99% of affected individuals. Methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially those who have atypical findings or are too young to manifest sufficient features to make the diagnosis on clinical grounds.
  • Smith-Magenis syndrome (SMS) is characterized by distinctive facial features, developmental delay, cognitive impairment, and behavioral abnormalities. The facial appearance is characterized by a broad square-shaped face, brachycephaly, prominent forehead, synophrys, mildly upslanting palpebral fissures, deep-set eyes, broad nasal bridge, midfacial retrusion (formerly known as midfacial hypoplasia), short, full-tipped nose with reduced nasal height, micrognathia in infancy changing to relative prognathia with age, and a distinct appearance of the mouth, with fleshy everted vermilion of the upper lip. Individuals with SMS have a wide degree of variability in cognitive and adaptive functioning, with the majority of individuals with SMS functioning in the mild-to-moderate range of intellectual disability. The behavioral phenotype includes significant sleep disturbance, stereotypies, and maladaptive and self-injurious behaviors. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping or need to be awakened for feeds, and generalized lethargy. SMS is caused by either detection of an interstitial deletion of 17p11.2 or by molecular genetic testing of RAI1. A visible interstitial deletion of chromosome 17p11.2 can be detected in all individuals with the common deletion by a routine G-banded analysis provided the resolution is adequate (550 band or higher). Molecular genetic testing of RAI1, the only gene in which mutation or deletion is known to account for a majority of features in SMS, is performed for individuals in whom a FISH- or aCGH-detectable deletion has been excluded.
  • Aicardi syndrome (AIS) is characterized by a triad of features: agenesis of the corpus callosum, distinctive chorioretinal lacunae, and infantile spasms. However, it is now well recognized that several other important findings are typically present in girls with Aicardi syndrome. Neurologic examination can reveal microcephaly, axial hypotonia, and appendicular hypertonia with spasticity. Moderate to severe global developmental delay and intellectual disability are expected. Many girls with Aicardi syndrome develop seizures prior to age three months, and most before age one year. Ongoing medically refractory epilepsy with a variety of seizure types develops over time. Costovertebral defects are common and can lead to marked scoliosis in up to one third of affected individuals. Other signs include characteristic facial features, gastrointestinal difficulties, small hands, vascular malformations and pigmentary lesions of the skin, increased incidence of tumors, lower growth rate after ages seven to nine years, and precocious or delayed puberty. Survival is highly variable, with the mean age of death about 8.3 years and the median age of death about 18.5 years.

Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to Image SimulConsult.jpg, an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with 1p36 deletion syndrome, the following evaluations are recommended:

  • Measurements of growth parameters and plotting on standard growth charts
    Note: No growth charts are available specifically for 1p36 deletion syndrome.
  • Physical and neurologic examination
  • Evaluation of cognitive, language, and motor development and social skills
  • Examination of the heart (auscultation, electrocardiogram, echocardiography) in infancy
  • Waking/sleeping video-EEG-polygraphic studies (mainly in infancy) to detect infantile spasms with hypsarrhythmia
  • Evaluation for feeding problems and gastroesophageal reflux with referral to a dysphagia team
  • Ophthalmology consultation in infancy or at diagnosis even in the absence of overt anomalies
  • Physical examination for skeletal anomalies (e.g., scoliosis, lower-limb asymmetry); if anomalies are present, referral for orthopedic and physical therapy evaluation
  • Comprehensive otolaryngologic evaluation and audiologic screening (brain stem auditory evoked responses) as early as possible to allow appropriate interventions
  • Renal function testing and renal ultrasonography in infancy to detect structural renal anomalies
  • Periodic thyroid function screening
  • Medical genetics consultation

Treatment of Manifestations

Intellectual disability. Enrollment in a personalized rehabilitation program with attention to motor development, cognition, communication, and social skills is appropriate [Battaglia et al 2008]. Use of sign language enhances communication skills and does not inhibit the appearance of speech. Early intervention and, later, appropriate school placement are essential.

Seizures. Up to 25% of persons with 1p36 deletion syndrome develop infantile spasms associated with a hypsarrhythmic EEG; the spasms are responsive to ACTH.

In most individuals, all seizure types are well controlled by standard antiepileptic drugs (AEDs), provided that the first-choice drug is started as early as possible.

Feeding difficulties. Feeding therapy with attention to oral motor skills is appropriate. Special feeding techniques or devices, e.g., the "Haberman feeder," can be used for feeding a hypotonic infant/child without a cleft palate or those with an unrepaired cleft palate. Gavage feeding is recommended for those with poorly coordinated swallow. Gastroesophageal reflux should be addressed in a standard manner. In one study, a few individuals with 1p36 deletion syndrome were managed with gastrostomy [Heilstedt et al 2003b].

Congenital heart defects are usually not complex and are amenable to repair. "Non-compaction" cardiomyopathy responds well to the standard pharmacotherapy (e.g., furosemide, captopril, digoxin) [Battaglia et al 2008].

Ophthalmologic abnormalities are treated in the standard manner. Visual inattentiveness, reported in up to 64% of individuals with 1p36 deletion syndrome, can be treated with an appropriate rehabilitation program [Bolognini et al 2005, Battaglia et al 2008].

Skeletal abnormalities (e.g., scoliosis, lower-limb asymmetry) need to be addressed on an individual basis. Early treatment (both physical therapy and surgery) is suggested.

Hearing loss is treated with a trial of hearing aids.

Other. Structural anomalies (e.g., gastrointestinal, renal) should be addressed in a standard manner. Hypothyroidism is treated in a standard manner.

Surveillance

Systematic follow-up allows for adjustment of rehabilitation and treatment as skills improve or deteriorate and medical needs change [Battaglia et al 2008].

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

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. —ED.

Mode of Inheritance

1p36 deletion syndrome can be the result of an inherited or de novo chromosome abnormality.

Risk to Family Members

Parents of a proband

Sibs of a proband

Offspring of a proband. No individual with 1p36 deletion syndrome is known to have reproduced.

Other family members of a proband. If a parent carries a chromosome rearrangement, his or her family members are also at risk of carrying the rearrangement.

Carrier Detection

If a parent of the proband has a balanced chromosome rearrangement, at-risk family members can be tested by the method used to identify the rearrangement in the parent (i.e., chromosome analysis or subtelomeric FISH analysis).

Related Genetic Counseling Issues

Specific counseling issues. Specific empiric risks for translocations involving 1p and another chromosome are unknown.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are known to be or at risk of being carriers of a chromosome rearrangement.

Prenatal Testing

High-risk pregnancy. Prenatal testing is possible for families who have had a child with 1p36 deletion syndrome and in families in which one parent is known to be a carrier of a chromosome rearrangement. Cells obtained by chorionic villus sampling (CVS) at approximately ten to 12 weeks' gestation or amniocentesis usually performed at approximately 15 to 18 weeks' gestation can be analyzed by a combination of cytogenetic methods (G-banding, FISH, and whole chromosome painting) depending on the specific findings in the proband and parent.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Preimplantation genetic diagnosis (PGD) may be an option for some couples at risk of having a pregnancy with 1p36 deletion syndrome caused by inherited chromosome rearrangement.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Chromosome Disorder Outreach (CDO)
    PO Box 724
    Boca Raton FL 33429-0724
    Phone: 561-395-4252 (Family Helpline)
    Email: info@chromodisorder.org
  • Unique: The Rare Chromosome Disorder Support Group
    PO Box 2189
    Caterham Surrey CR3 5GN
    United Kingdom
    Phone: +44 (0) 1883 330766
    Fax: +44 (0) 1883 330766
    Email: info@rarechromo.org; rarechromo@aol.com

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A. 1p36 Deletion Syndrome: Genes and Databases

Gene SymbolChromosomal LocusProtein Name
Not applicable1p36Not applicable

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B. OMIM Entries for 1p36 Deletion Syndrome (View All in OMIM)

607872CHROMOSOME 1p36 DELETION SYNDROME

Molecular Genetic Pathogenesis

No genes have been conclusively determined to be associated with the clinical features that characterize 1p36 deletion syndrome.

References

Literature Cited

  1. Anderson J, Kempski H, Hill L, Rampling D, Gordon T, Michalski A. Neuroblastoma in monozygotic twins--a case of probable twin-to-twin metastasis. Br J Cancer. 2001;85:493–6. [PMC free article: PMC2364085] [PubMed: 11506485]
  2. Bahi-Buisson N, Gutierrez-Delicado E, Soufflet C, Rio M, Cormier Daire V, Lacombe D, Heron D, Verloes A, Zuberi SM, Burglen L, Afenjar A, Moutard LM, Edery P, Dulac O, Nabbout R, Plouin P, Battaglia A. Spectrum of epilepsy in terminal 1p36 deletion syndrome. Epilepsia. 2008;49:509–15. [PubMed: 18031548]
  3. Battaglia A. Del 1p36 syndrome: a newly emerging clinical entity. Brain Dev. 2005;27:358–61. [PubMed: 16023552]
  4. Battaglia A, Hoyme HE, Dallapiccola B, Zackai E, Hudgins L, McDonald-McGinn D, Bahi-Buisson N, Romano C, Williams CA, Braley LL, Zuberi SM, Carey JC. Further delineation of deletion 1p36 syndrome in 60 patients: a recognizable phenotype and common cause of developmental delay and mental retardation. Pediatrics. 2008;121:404–10. [PubMed: 18245432]
  5. Biegel JA, White PS, Marshall HN, Fujimori M, Zackai EH, Scher CD, Brodeur GM, Emanuel BS. Constitutional 1p36 deletion in a child with neuroblastoma. Am J Hum Genet. 1993;52:176–82. [PMC free article: PMC1682134] [PubMed: 8434586]
  6. Bolognini N, Rasi F, Coccia M, Ladavas E. Visual search improvement in hemianopic patients after audio-visual stimulation. Brain. 2005;128:2830–42. [PubMed: 16219672]
  7. Descartes M, Mikhail FM, Franklin JC, McGrath TM, Bebin M. Monosomy1p36.3 and trisomy 19p13.3 in a child with periventricular nodular heterotopia. Pediatr Neurol. 2011;45:274–8. [PubMed: 21907895]
  8. Dobyns WB, Mirzaa G, Christian SL, Petras K, Roseberry J, Clark GD, Curry CJR, McDonald-McGinn D, Medne L, Zackai E, Parsons J, Zand DJ, Hisama FM, Walsh CA, Leventer RJ, Martin CL, Gajecka M, Shaffer LG. Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36, 2p16.1-p23.1, 4q21.21-q22.1, 6q26-q27, and 21q2. Am J Med Genet A. 2008;146A:1637–54. [PMC free article: PMC2801020] [PubMed: 18536050]
  9. Gajecka M, Mackay KL, Shaffer LG. Monosomy 1p36 deletion syndrome. Am J Med Genet C Semin Med Genet. 2007;145C:346–56. [PubMed: 17918734]
  10. Gajecka M, Saitta SC, Gentles AJ, Campbell L, Ciprero K, Geiger E, Catherwood A, Rosenfeld JA, Shaikh T, Shaffer LG. Recurrent interstitial 1p36 deletions: evidence for germline mosaicism and complex rearrangement breakpoints. Am J Med Genet A. 2010;152A:3074–83. [PMC free article: PMC3058890] [PubMed: 21108392]
  11. Haimi M, Iancu TC, Shaffer LG, Lerner A. Severe lysosomal storage disease of liver in del(1)(p36): a new presentation. Eur J Med Genet. 2011;54:209–13. [PubMed: 21145995]
  12. Halpern AV, Bansal A, Heymann WR. Pemphigus vulgaris in a patient with 1p36 deletion syndrome. J Am Acad Dermatol. 2006;55 Suppl 5:98–9. [PubMed: 17052548]
  13. Heilstedt HA, Ballif BC, Howard LA, Kashork CD, Shaffer LG. Population data suggest that deletions of 1p36 are a relatively common chromosome abnormality. Clin Genet. 2003a;64:310–6. [PubMed: 12974736]
  14. Heilstedt HA, Ballif BC, Howard LA, Lewis RA, Stal S, Kashork CD, Bacino CA, Shapira SK, Shaffer LG. Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome. Am J Hum Genet. 2003b;72:1200–12. [PMC free article: PMC1180272] [PubMed: 12687501]
  15. Heilstedt HA, Burgess DL, Anderson AE, Chedrawi A, Tharp B, Lee O, Kashork CD, Starkey DE, Wu YQ, Noebels JL, Shaffer LG, Shapira SK. Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome. Epilepsia. 2001;42:1103–11. [PubMed: 11580756]
  16. Kanabar G, Boyd S, Schugal A, Bhate S. Multiple causes of apnea in 1p36 deletion syndrome include seizures. Seizure. 2012;21:402–6. [PubMed: 22425009]
  17. Kawashima H, Kinjo N, Uejima H, Ioi H, Takekuma K, Nagae I, Ishii K, Itoi T, Numabe H. A case of 1p36 deletion syndrome accompanied with anomalous arrangement of the pancreaticobiliary duct. Pancreas. 2011;40:171–3. [PubMed: 21160384]
  18. Keppler-Noreuil KM, Carroll AJ, Finley WH, Rutledge SL. Chromosome 1p terminal deletion: report of new findings and confirmation of two characteristic phenotypes. J Med Genet. 1995;32:619–22. [PMC free article: PMC1051636] [PubMed: 7473653]
  19. Laureys G, Speleman F, Opdenakker G, Benoit Y, Leroy J. Constitutional translocation t(1;17)(p36;q12-21) in a patient with neuroblastoma. Genes Chromosomes Cancer. 1990;2:252–4. [PubMed: 2078517]
  20. Minami K, Boshi H, Minami T, Tamura A, Yanagawa T, Uemura S, Takifuji K, Kurosawa K, Tsukino R, Izumi G, Yoshikawa N. 1p36 deletion syndrome with intestinal malrotation and annular pancreas. Eur J Pediatr. 2005;164:193–4. [PubMed: 15717182]
  21. Neal J, Apse K, Sahin M, Walsh CA, Sheen VL. Deletion of chromosome 1p36 is associated with periventricular nodular heterotopia. Am J Med Genet A. 2006;140:1692–5. [PubMed: 16835933]
  22. Okamoto N, Toribe Y, Nakajima T, Okinaga T, Kurosawa K, Nonaka I, Shimokawa O, Matsumoto N. A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy. J Hum Genet. 2002;47:556–9. [PubMed: 12376748]
  23. Paciorkowski AR, Thio LL, Rosenfeld JA, Gajecka M, Gurnett CA, Kulkarni S, Chung WK, Marsh ED, Gentile M, Reggin JD, Wheless JW, Balasubramian S, Kumar R, Christian SL, Marini C, Guerrini R, Maltsev N, Shaffer LG, Dobyns WB. Copy number variants and infantile spasms: evidence for abnormalities in ventral forebrain development and pathways of synaptic function. Eur J Hum Genet. 2011;19:1238–45. [PMC free article: PMC3230360] [PubMed: 21694734]
  24. Redon R, Rio M, Gregory SG, Cooper RA, Fiegler H, Sanlaville D, Banerjee R, Scott C, Carr P, Langford C, Cormier-Daire V, Munnich A, Carter NP, Colleaux L. Tiling path resolution mapping of constitutional 1p36 deletions by array-CGH: contiguous gene deletion or "deletion with positional effect" syndrome? J Med Genet. 2005;42:166–71. [PMC free article: PMC1735995] [PubMed: 15689456]
  25. Reish O, Berry SA, Hirsch B. Partial monosomy of chromosome 1p36.3: characterization of the critical region and delineation of a syndrome. Am J Med Genet. 1995;59:467–75. [PubMed: 8585567]
  26. Shapira SK, McCaskill C, Northrup H, Spikes AS, Elder FF, Sutton VR, Korenberg JR, Greenberg F, Shaffer LG. Chromosome 1p36 deletions: the clinical phenotype and molecular characterization of a common newly delineated syndrome. Am J Hum Genet. 1997;61:642–50. [PMC free article: PMC1715949] [PubMed: 9326330]
  27. Slavotinek A, Shaffer LG, Shapira SK. Monosomy 1p36. J Med Genet. 1999;36:657–63. [PMC free article: PMC1734434] [PubMed: 10507720]
  28. Wang BT, Chen M. Redundant skin over the nape in a girl with monosomy 1p36 caused by a de-novo satellited derivative chromosome: a possible new feature? Clin Dysmorphol. 2004;13:107–9. [PubMed: 15057128]
  29. Wu YQ, Heilstedt HA, Bedell JA, May KM, Starkey DE, McPherson JD, Shapira SK, Shaffer LG. Molecular refinement of the 1p36 deletion syndrome reveals size diversity and a preponderance of maternally derived deletions. Hum Mol Genet. 1999;8:313–21. [PubMed: 9931339]

Chapter Notes

Author History

Agatino Battaglia, MD (2008-present)
Lisa G Shaffer, PhD, FACMG; Signature Genomic Laboratories (2008-2013)

Revision History

  • 6 June 2013 (me) Comprehensive update posted live
  • 1 February 2008 (me) Review posted to live Web site
  • 24 August 2007 (ab) Original submission
Copyright © 1993-2014, University of Washington, Seattle. All rights reserved.

For more information, see the GeneReviews Copyright Notice and Usage Disclaimer.

For questions regarding permissions: ude.wu@tssamda.

Bookshelf ID: NBK1191PMID: 20301370
PubReader format: click here to try

Views

Tests in GTR by Condition

Related information

  • MedGen
    Related information in MedGen
  • OMIM
    Related OMIM records
  • PMC
    PubMed Central citations
  • PubMed
    Links to pubmed

Related citations in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...