Genetic counseling: 1p36 Deletion Syndrome-1

1p36 Deletion Syndrome

Introduction

 * Introduce myself and acknowledge that I will be involved in their visit today.
 * Let them know that Counselor1 and Dr. Doktour will also be visiting with them today.
 * Small talk while walking to the room.
 * "What are your main concerns or questions that you would like addressed today?"

Interim History

 * Explain that all of their concerns will be addressed later in the session, but that I would like to update the medical and developmental history from her last visit in February.
 * Who is her pediatrician? Any other physicians?
 * Any serious illnesses, hospitalizations or surgeries since February?
 * Current Medications?
 * Immunizations up to date?

Review of Systems

 * Any diet or feeding concerns?
 * Any changes in skin pigmentation or birth marks?
 * Any heart concerns? (cardiologist found none)
 * Any bladder problems?
 * Any concerns about her hearing? Ear infections? PE tubes?
 * Any concerns with her behavior or sleep?
 * Any bowel problems? Constipation?
 * Any allergies?
 * Any concerns about vision or eyes?
 * Any concerns about seizures? Starring spells or repetitive behaviors?
 * Any other medical concerns (difficulty breathing)

Developmental Assessment

 * Language
 * How many words does she have in her vocabulary?
 * Is she learning to sign? How many signs does she know?
 * Does she combine words into two word sentences?
 * Does she follow one or two step commands?
 * Can she point to any body parts?
 * How well is she able to indicate her wants?
 * Gross Motor
 * Is she standing independently?
 * Is she cruising?
 * Is she walking? Up stairs?
 * Visual Motor
 * How well does she hold and manipulate a crayon?
 * Drink from a cup?
 * Uses a spoon to feed? Started using a fork?
 * Can she help undress or dress herself?
 * Social
 * Imitates housework?
 * Behavior? (Rocking)


 * How do you feel her development compares with other children?
 * Do you feel she is making progress?

Early Intervention

 * Ask about OT, PT and speech therapy.
 * How often?
 * Where is she receiving services?
 * What are they working on and what are the goals?
 * Is insurance covering these costs?
 * How do you think she is progressing?

Psychosocial Assessment

 * Are all your other children living at home?
 * Things must be really hectic attending all her appointments and services on top of having ____ other children at home. How does it all work out?
 * Do you have help from other family members or others?
 * Do you have contact with any other families with 1p36 deletion syndrome?

Etiology of 1p36 deletion syndrome (monosomy 1p36)

 * Caused by deletion of the most distal band of the short arm of chromosome1.
 * Most clinical manifestations are probably caused by the absence of one copy of a dose-sensitive gene and it is not possible to replace missing genes from chromosomes at this time.
 * Prevalence of this deletion is estimated to be 1 in 10,000 to as high as 1 in 5,000 (making it the most common terminal deletion)
 * Most cases result from sporadic deletions and are not inherited
 * 1p36 deletion syndrome is usually diagnosed through recognition of the symptoms and characteristics as well as lab testing. This is done using high resolution chromosome analysis, or FISH with a chromosome 1-specific subtelomeric probe. The deletion often doesn't show up clearly with standard cytogenetic banding techniques. (In one group studied, about half were missed with chromosome analysis)
 * Patients with a 1p36 deletion have different sized pieces of the chromosome missing and may result in phenotype variability
 * Severity of associated disorders varies, but the physical features are very similar
 * Degree of MR and ability to acquire complex speech is somewhat dependent on deletion size
 * Most deletions affect the chromosome inherited from the mother (68%), but there doesn't seem to be differences in the clinical manifestations based on whether the deletion is on the paternal or maternal chromosome.
 * Those with paternally derived deletions tend to have larger deletions than those with maternally derived deletions
 * Mechanism causing chromosome breakage is unknown

Characteristics

 * Children with 1p36 deletion syndrome are all unique individuals, but do have some common characteristics.
 * Distinct facial features including: small and pointed chin, flat nasal bridge, low-set ears, ear asymmetry, thickened ear helices, small head, deep-set eyes, large anterior fontanel, clinodactyly and/or short fifth finger
 * Most patients have mental retardation
 * Most patients have delayed growth and/or difficulty gaining weight. Some have difficulty with sucking and swallowing while others may not grow well even though they eat well. Some older children may become obese.
 * Most young children with 1p36 deletion syndrome have delayed development.
 * They sit up, walk and talk later than typical children.
 * Speech is severely affected with many patients learning only a few words
 * Other medical problems: hypotony (which may explain delayed motor skills), hearing loss, seizures, eye/vision problems, hypothyroidism, increased risk for neuroblastoma, heart defects (which have included cardiomyopathy, ductus arteriosus, tetralogy of Fallot, VSD), and orofacial clefting abnormalities,

Recurrence Risk for next pregnancy

 * The majority of patients with 1p36 deletion syndrome are isolated cases resulting from a de novo deletion. There have been reports of patients with 1p36 deletion syndrome whose parents have a balanced translocation.
 * Parents should be tested for chromosomal rearrangements because about 6% of parents with an affected child have a balanced translocation
 * Translocation increases the chances of having another child with a 1p36 deletion.
 * If no translocation is found the chances of having another child with a 1p36 deletion are very small

Prenatal Diagnosis

 * In 1999 a case was reported in which a 1p36 deletion in a fetus was detected when an amniocentesis was performed due to detection of multiple malformations on ultrasound
 * Another case was picked up prenatally because of the presence of elevated maternal serum alpha-fetoprotein (no abnormal sign seen on ultrasound).
 * Another was diagnosed prenatally because the mother was known to have a balanced translocation between the short arms of chromosome 1 and 20 that was picked up after their first child had inherited an unbalanced product. (no abnormal sign seen on ultrasound)

Medical Treatment

 * Seizures can usually be controlled with medication
 * Medical interventions and feeding therapy may be needed to manage feeding issues
 * Early Intervention for developmental delay
 * Surgery may be necessary to correct heart defects, cleft lip, cleft palate if present
 * A urine screen for neuroblastoma should be performed every 6 months
 * Physical examinations should involve palpating the abdomen for lumps which might be neuroblastomas
 * There are no clear indications on whether they should continue to be followed by a cardiologist or whether the cardiomyopathy is limited to a congenital form.

Psychosocial Issues

 * Initially parents may experience denial about how severe the developmental delay and mental retardation will be
 * Blaming of self or partner may occur
 * Stress of having a child with developmental delays and mental retardation
 * Stress associated with having a child with serious medical problems especially if they have heart malformations or seizures
 * Fear that the child might develop a neuroblastoma or seizures
 * Time commitment involved with early intervention services (OT, PT, speech therapy)

Patient Resources

 * Chromosome Deletion Outreach
 * MUMS