Term
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Definition
- Deletion of material on long arm of 13
Clinical features include:
- Developmental delay/ID
- Retinoblastoma & wide set eyes
- Brain/heart defects
- Renal abnormalities
- Delayed skeletal maturation
- Dysmorphic features (short nose, prominent philtrum and forehead)
- These children have a shortened lifespan but can live to adulthood
- Need cardiologist and retinoblastoma screening |
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Term
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Definition
- An additional chromosome 9 in some of the body's cells
- Highly variable depending on mosaicism
Clinical features include:
- Developmental delays/ID
- Heart defects
- Respiratory defects
- Feeding/gastric difficulties
- Renal issues
- JOINT ANOMALAIES
- Seizures
- Bulbous nose, small eyes, small jaw
- Limited survivability |
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Term
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Definition
- Also called Cri du Chat syndrome
- Deletion on chromosome 5, mostly de novo
Clinical features include:
- Distinctive cry (gone by 2)
- Intellectual disability
- Less expressive communication, spastic gait, coordination problems, friendly, hyperactive
- Round face, simian crease, epicanthal folds, other malformations possible
- Normal life expectancy |
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Term
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Definition
- Also called Wolf-Hischron Syndrome
- Most mutations sporadic
Clinical features include:
- "Greek helmet faces," micrognathia, cleft palate, missing teeth, wide set eyes, droopy eyelids
- Hearing loss
- Intellectual disability & developmental delay
- Seizures
- Hypotonia
- Other (cardiac, renal, skeletal) abnormalities
- 35% pass away within first two years of life, some live to 30s, 40s |
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Term
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Definition
- Highly variable phenotype correlating with size of the deletion
Clinical features include:
- Developmental delay & ID
- Wide, "carp like" mouth
- Hearing impairment
- Proximally placed thumbs
- Seizures, autism, vision problems
- High risk of early death but variation, can live into adulthood |
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Term
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Definition
- Two normal copies of chromosome 15 plus an additional isodicentric chromosome from mom
Clinical features include:
- Developmental delays/ID
- Autistic
- Epilepsy
- Hypotonia
- Normal life span, but risk of death from seizures |
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Term
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Definition
- Also called Patau Syndrome
Clinical Features: THINK MIDLINE ISSUES
- Severe intellectual disability
- Heart defects
- Holoprosencephaly (Forebrain fails to develop)
- Small eyes, cyclopia
- Polydactyly
- Low survival rate |
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Term
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Definition
- Edwards Syndrome
Clinical features:
- Developmental delay, profound ID
- Clenched hands
- Club feet
- Cardiovascular issues 90% of time
- Gastrointestinal issues
- 90-95% mortality first year |
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Term
| Osteogenesis Imperfecta Type II |
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Definition
- The most severe form of OI
- Considered prenatal/perinatal lethal
- Disease caused by mutation to collagen producing genes
- Usually de novo. Dominant lethal.
Clinical features:
- Skeletal abnormalities (wormian bones in skull, flat vertebrate)
- Signs of prenatal fracturing (beaded ribs, broken bones)
- Complications in pregnancy (hydrops fetalis, early birth)
- After birth, pulmonary and cardiac insufficiency and brittle bones
- These children usually die in the first few weeks of life |
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Term
| Congenital Adrenal Hyperplasia (CAH) |
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Definition
- A group of disorders that affects the adrenal glands. Because of this, levels of cortisol (stress hormone), aldosterone (salt and potassium levels), and androgens (testoterone) are unbalanced.
- Autosomal recessive
Clinical Features include:
- Ambiguous genitalia in females
- Lack of cortisol causes blood pressure and blood sugar issues
- Lack of aldosterone causes blood pressure problems and low sodium
- Additional male sex hormones causes early puberty, hairiness, fertility issues
- In severe cases adrenal crisis can occur
- Without treatment adrenal crisis can cause vomiting, dehydration, shock and even death |
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Term
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Definition
- Micro-deletion syndrome (autosomal dominant)
Clinical characteristics:
- Cardiovascular disease (pumonary stenosis)
- Connective tissue abnormalities
- Intellectual disabilities
- Over friendliness and anxiety
- Star-like pattern in eyes, broad forehead, shorter
- Hearing loss, and sensitivity to noise
- Endocrine abnormalities (hypercalcemia, hypothyroidism)
- Risk of sudden death from heart defects |
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Term
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Definition
- AKA, 22q, velocardiofacial syndrome
- A micro-deletion syndrome
Characteristics include:
- Heart defects (tetrology of fallot, vsd, etc)
- Facial features (cleft palate, underdeveloped chin, wide-set eyes)
- Decreased immune system
- Delayed growth, ID
- Behavioral and emotional problems |
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Term
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Definition
- Monosomy X
- The majority of conceptions are lost prenatally
Clinical characteristics:
- Small stature, shield-like chest, webbed neck
- High functioning but maybe some learning differences
- Infertility
- Cardiac problems are common! |
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Term
| Ornithine Transcarbamylase (OTC) deficiency |
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Definition
- Inborn error of metabolism
- Urea cycle disorder. It results in the accumulation of ammonia in the blood since body can't remove nitrogen.
- X-linked
Clinical characteristics:
- Lethargy
- Seizures
- Vomiting
- Ongoing nerologic problems such as developmental delay, intellectual disability, ADHD
- Hyperammonemic coma (causes damage) and death possible
- Like other inborn errors of metabolism, can happen a few days after birth or be later onset. Often onset by stress.
- Protein restricted diet supplement essential amino acids |
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Term
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Definition
- A disease that alters the connective tissues in the body
- Fibrillin-1 point mutation
Clinical characteristics:
- Long arms, legs, fingers
- Sunken or protruding chests
- Flat feet
- Cardiac issues such as aortic root dilation (or dissection) or mitral valve prolapse
- Ectopia lentis (dislocated lenses) |
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Term
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Definition
- A disease that is characterized by spots on the skin
- Autosomal dominant, but 50% due to new mutations
Clinical characteristics:
- Dark spots on skin, small skin tumors called neurofibromas
- Lisch nodules, or benign growths in eyes
- Learning differences
- Malignancies happen about 10% of the time
- This disease is highly variable. For 2/3 of people it is a mild skin disorder. For about 1/12 it is life threatening. |
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Term
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Definition
- Inborn error of metabolism
- Autosomal recessive
Clinical characteristics:
- Hyperphenylalaneinemia (body can't break down phenylalanine, so there is a lot in the blood)
- Microcephaly
- Epilepsy
- Severe mental delays
- Urine will have a mousy smell
- Manage the protien diet and supplement essential amino acids |
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Term
| Osteogenesis Imperfecta (OI) |
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Definition
- A disease of improper bone formation
- Caused by mutations in the collagen forming genes
- Mostly autosomal dominant, some autosomal recessive
Clinical characteristics:
- Bones break easily
- Hearing loss
- Discolored sclerae (white part of the eye)
- A lot of variation, can be prenatal lethal or fairly mild |
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Term
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Definition
| Tumor suppressor genes involved in DNA repair. They help with “cell checkpoints” before replication. They are one of the major causes of hereditary breast cancer and ovarian cancer. They also cause a risk for prostate cancer and pancreatic cancer. However, we can’t actually give a hard number about how much having a mutation in these genes increases your risk. |
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Term
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Definition
A classic but rare hereditary cancer syndrome associated with the TP53 gene.
Autosomal dominant.
There is a 50% risk of cancer by 40, 90% by 60. These cancers are usually breast (frequent in women), and the kinds of cancers usually seen in children (like bone, soft tissue sarcomas, brain cancers, and leukemia).
Adrenocortical tumors are fairly specific to this syndrome as are malignant phyllodes tumors.
There is a risk of multiple primary cancers and a risk of radiation-related secondary cancers. Someone with this syndrome follows the “toronto protocol” of whole body MRI screening. |
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Term
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Definition
Rare hereditary cancer syndrome associated with the PTEN gene.
Autosomal dominant.
These cancers are usually mucocutaneous lesions. They can happen on the face, lips, tongue, or the oral mucosa. There is also a lifetime risk of breast cancer, thyroid cancer, endometrial cancer, and renal cancer. This is also a colon cancer syndrome.
To diagnose this, look out for macrocephaly and a history of breast cancer, thyroid cancer, and skin tags. Intellectual disability is also telling. |
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Term
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Definition
AUTOSOMAL RECESSIVE neurodegenerative syndrome that causes severe disability. They also have a high risk of radiation-induced cancer.
Being a carrier for the ATM gene is also a cancer syndrome.Female carriers have an elevated risk of breast cancer. There is not enough evidence to say radiation affects them similarly. |
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Term
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Definition
PALB2 stands for Partner and Localizer of BRCA2. It is autosomal dominant.
Causes an increased risk of breast cancer and pancreatic cancer. Really think about this gene with pancreatic families. |
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Term
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Definition
| CHEK2 stands for Checkpoint Kinase 2. It is part of the BRCA pathway. It causes an increased risk of breast cancer but is more like a risk factor/moderate penetrance. We know this because people can have two mutations. |
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Term
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Definition
An autosomal recessive hereditary cancer disorder that is tied into the BRCA pathway. You need to inherit two broken copies of BRCA1.
People with this disorder can have physical differences, such as short stature, and often have bone marrow failure or leukemia. |
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Term
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Definition
| Also called hereditary diffuse gastric cancer syndrome. It is associated with an increased risk of lobular breast cancer and gastric cancers. |
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Term
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Definition
Having two NBN mutations is associated with Nijmegan (pronounced knee-ma-gin) breakage syndrome.
This is an autosomal recessive disorder that causes growth retardation, immunosuppression, and cancer risk. Heterozygotes have an increased risk of breast cancer. |
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Term
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Definition
STK11 gene. Higher penetrance risk of breast cancer (50% lifetime risk) and GI hamartomas. Also a colon cancer syndrome.
This has characteristic pigmentation of the lips -- it looks like they have spots of blue-black ink. |
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Term
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Definition
Autosomal dominant neurodegenerative disease. Leads to problems with movement, emotion, and cognition.
Clinical features include:
- Jerky, involuntary movements
- Speech or swallowing difficulties
- Slowed thinking
- Irritibility, mania, OCD, anxiety, depression
Pre-symptomatic testing is available.
The disease is due to an unstable CAG repeat, which can expand in successive generations causing anticipation. More likely to anticipate when passed from fathers to children. |
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Term
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Definition
Autosomal recessive. A disease caused by excessive absorption of iron. Symptoms begin 40-60 (after menopause in women).
Clinical features include:
- Hepatomegaly (large liver)
- Cirrhosis of the liver
- Diabetes
- Arrhythmia
- Arthritis
- Skin pigmentation
Later stages can cause liver disease and heart failure. It can be treated by bleeding.
Carrier frequency in Caucasians 1/9 but penetrance varies. |
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Term
| Early-Onset Familial Alzheimer's Disease |
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Definition
To be considered early onset, under age 65. Autosomal dominant. Makes up to 3-10% of Alzheimers.
Clinical features include:
- Confusion
- Memory loss, language deficits
- Agitation, withdrawal
- Hallucinations
- Seizures
- Increased muscle tone
Brain findings show increased B-amyloid plaque formation and intraneuronal neruofibrillary tangles.
There are gene panels, molecular testing, and predictive testing. |
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Term
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Definition
Most common type of muscular dystrophy in adults. Autosomal dominant trinucleotide repeat disorder (has premutations and mutations, more common to inherit through mother).
Clinical features:
- Myotonia is sustained muscle contraction, so inability to loosen grasp
- Cataracts
- Fatigue, pain
- Cardiac complications
- Lower IQ
- Hypersomnia
- Anxiety, depression
- Inverted V -shaped upper lip, droopy eyelids
Prenatal and molecular testing available. |
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Term
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Definition
MELAS stands for Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Mitochondrial inborn error of metabolism.
Clinical features include:
- Seizures
- Recurrent headaches
- Stroke-like episodes (can lead to loss of motor skills or intellectual disability)
- Lactic acidosis
- Abdominal pain, vomiting
- Exercise intolerance, muscle weakness
- Difficulty breathing
- RAGGED RED FIBERS
Mutation in mitochondrial DNA, disrupts respiratory chain. Therefore, mitochondrial inheritance.
Variety due to HETEROPLASMY |
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Term
| Young Onset Parkinson's Disease |
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Definition
If Parkinson's disease occurs before 50 it is considered young onset. In this case it is less likely to be multifactorially inherited and more likely to be due to a causative gene. These causative genes are numerous and can have any mode of inheritance.
Clinical features include:
- Motor symptoms like tremors, muscle rigidity, slow movement, involuntary movement
- Cognitive features like mood disorders, problems focusing, or hallucinations
- Other symptoms like pain, loss of sense of smell, or urinary urgency
- People with young onset Parkinsons will generally have more involuntary movement and fewer cognitive symptoms
Can be treated with replacement dopamine medication and therapies. Direct to consumer tests are available. |
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Term
|
Definition
Stands for mitochondrial neurogastrointestinal encephalopathy.
Clinical features include:
- Gastrointestinal issues (pain, vomiting)
- Neuropathy (numbness, pain in extremities)
- Hearing loss
- Leukoencephalopathy (white brain matter disease)
- Droopy eyelids
Even though this is a mitochondrial disease it is AUTOSOMAL RECESSIVE. It is caused by not being able to break down thymidine, which builds up and hurts mitochondria.
To test for it, you can test for Thymidine Phosporylase Enzyme Activity or the level of thymidine. |
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Term
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Definition
Stands for Cerebral Autosomal Dominant Arteriopathy Subcortical Infaracts Leukoencephalopathy.
Clinical features include:
- Recurrent strokes
- Cognitive impairment
- Migraine with aura
- Psychiatric disturbances
Gene mutation causes smooth muscle cells on the walls of the arteries to break down. Progressive damage to blood vessels in the brain causes stroke and other symptoms.
Autosomal dominant, varies greatly. Genetic testing available. |
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Term
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Definition
A neural tube defect in the formation of the spine. Leads to a protrusion of spinal fluid or the spinal chord.
Considered a major birth defect.
Clinical features include:
- Neurologic deficit
- Areas without sensation
- Muscle weakness
- Secondary complications like hydrocephaly
Lifelong complications include:
- Paraplegia
- Bladder/fecal incontinence
- Skeletal deformation
- Occasionally metal impairment
Multifactorial condition. See risk tables for recurrence risk.
Risk can be decreased by taking folate. Risk is increased with fever early in pregnancy or anti-seizure medication.
Can be picked up by ultrasound or an increased AFP. |
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Term
| Polycistic Kidney Disease |
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Definition
Can be autosomal dominant or autosomal recessive. Autosomal recessive more severe, discussed here. Liver and kidney related morbidity.
Clinical features include:
- Enlarged kidneys, cysts in kidneys, kidney failure
- Liver and spleen issues like enlarged liver and spleen
- Pulmonary hypoplasia
- Facial features like low set ears, flattened nose, or micrognathia
Ciliary disease. Survival decreased. Prenatal diagnosis available. |
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Term
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Definition
A short-limb dwarfism syndrome. Lethal in the perinatal period.
Ultrasound findings to diagnose with:
- Increased NT, shortened long bones
- Narrow thoracic cage with short ribs
- Growth deficiency
- Cloverleaf skill
Lethal due to respiratory insufficiency. Long term survival is rare. |
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Term
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Definition
The bowel -- typically the intestines -- are exposed through the abdominal wall, usually to the right of the cord.
These are not covered by an abdominal sac and are exposed to amniotic fluid. They are often seen in first pregnancies, especially teenagers.
About 15% associated with additional genetic anomalies. Considered multifactorial. |
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Term
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Definition
The bowel -- typically the organs and liver -- are exposed through a herniation in the umbilical chord. They are covered by a sac.
This is more likely to be seen in older women.
More than half of these babies have other birth defects. Smaller omphalocele are more indicative.
This is considered multifactorial. |
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Term
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Definition
X-linked recessive
A skin disorder that affects males. Caused by an INBORN ERROR OF METABOLISM. Often associated with Kallmann syndrome (they are next to each other on the X-chromosome).
Clinical features include:
- Brownish scales on trunk, back, arms
- Undescended testes, increased risk of malignancies,
- Comma-shaped corneal opacities (doesn't affect vision)
Caused by a deficiency of steroid sulfatase, which metabolizes cholesterol sulfate. This accumulates and the skin sticks together.
Diagnosed prenatally by low uE3, unconjugated estriol. Mothers may experience delay in labor. |
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Term
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Definition
X-linked recessive
The main feature of this syndrome is a delay or absence of puberty. Often associated with X-linked ichthyosis (they are next to each other on the X chromosome).
Clinical characteristics include:
- Delayed/absent puberty
- Anosmia (no sense of smell)
- Micropenis
- Undescended testes
- Facial abnormalities like cleft lip
- Disproportionately long arms
- Decreased muscle mass
- Deafness
- Movement of one hand mirrored in the other
Caused by a deficiency in gonadotropin-releasing hormone.
Diagnosed prenatally through ultrasound or when puberty doesn't occur. |
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Term
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Definition
Causes the loss of motor neurons in the spinal cord. Autosomal recessive inheritance.
Clinical features include:
- Muscle weakness leading to paralysis
- Hypotonia
- Twitching of the tongue
- Scoliosis
- Bell-shaped chest
- Sucking, breathing, or swallowing problems
Only 2% de novo rate. The later the symptoms onset, the milder the course of the disease.
Caused by a mutation in the SMN1 gene. There is a SMN2 gene too as a backup -- the more SMN2 you have the milder the disease. |
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Term
| Familial Adenomatous Polyposis (FAP) |
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Definition
The penetrance for adenomas for people with this condition is 100%. “Carpeted” with polyps. Autosomal dominant.
High colon cancer risk if polyps not dealt with. Also have a risk of other GI cancers, thyroid, and brain cancers.
One clinical sign of this syndrome is CHRPE.
Management is to do a sigmoidoscopy from age 10 until polyps develop, then switch to colonoscopy to remove. Might get a colectomy. |
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Term
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Definition
A subtype of FAP. It is later onset and there are fewer adenomatous polyps.
It is also not associated with CHRPE. Makes up 10% of FAP.
Tend to have mutations at end of the APC gene or a complete deletion. They tend to get about 30 adenomatous polyps. Management is colonoscopy every 2-3 years. |
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Term
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Definition
A variant of FAP. They have the features of FAP (including CHRPE) plus extraintestinal lesions.
They get desmoid tumors (tumors from the soft tissue), osteomas (jaw bone tumors), and skin tumors.
They also tend to have extra teeth. |
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Term
| Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) |
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Definition
| A pigmented lesion on the retina. Does not interfere with vision, but can be a marker for familial adenomatous polyposis (FAP). |
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Term
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Definition
A founder mutation of the Ashkenazi Jews (about 6%).
It creases a hypermutable area in the APC gene (the one associated with FAP). It causes a 2-fold increases in colorectal cancer risk, but it’s phenotype is the same as sporadic colorectal cancer. Does not look like other FAP. |
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Term
| MUTYH-Associated Polyposis (MAP) |
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Definition
Not as many polyps as FAP, but between 15 and 100. Many are adenomatous and some are hyperplastic. Autosomal recessive.
Two common mutations but over 80 are reported. Carriers have a 2-fold risk of colorectal cancer, but there are no specific screening recommendations. |
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Term
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Definition
A rare hereditary cancer syndrome. Causes adenomatous polyps and primary brain tumors.
Usually described as dominant, sometimes described as recessive.
Can be caused by an APC mutations (FAP).
This is associated with medulloblastomas (brain cancer). Can also be caused by PSM2/MLH1 (Lynch) mutations, which is associated with glioblastomas (another brain cancer). |
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Term
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Definition
A hamartomatous polyp condition (more risk than hyperplastic, less than adenomatous). Autosomal dominant.
Genes are Smad4 and BMPRIA.
It is considered Juvenile Polyposis if you have 5 juvenile polyps, polyps throughout the GI tract, or a family history of juvenile polyposis.
50 fold increase in colon cancer risk and an increase in GI cancer risk. Can be associated with Hereditary hemorrhagic telangiectasia (HHT). |
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Term
| Peutz-Jeghers Syndrome (colon) |
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Definition
A hamartomatous polyp condition (more risk than hyperplastic, less than adenomatous). Autosomal dominant.
Remember, this is the breast cancer syndrome that has the characteristic lip pigmentation that looks like blue ink. As well as being a breast cancer risk factor, Peutz-Jegher Syndrome can also cause GI cancers and a moderate amount of (less than 100) hamartomatous polyps. By 20 half of patients have symptoms such as GI bleeding, abdominal pain, and obstruction. Also associated with intussusception. |
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Term
| PTEN Hamartoma Tumor Syndrome (aka Cowden) (colon) |
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Definition
Considered a hamartomatous polyp condition (more risk than hyperplastic, less than adenomatous).
High risk of GI polyps of various kinds, an increased risk for colon cancer (about 9%). |
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Term
| Hereditary Mixed Polyposis Syndrome |
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Definition
| Increased risk of colon cancer due to a variety of polyp types including juvenile polyps (hamartomas), adenomatous polyps, hyperplastic polyps, inflammatory polyps, and more. Autosomal dominant inheritance. |
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Term
| Sessile Serrated Polyposis Syndrome |
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Definition
| Sessile (flat) polyps that have a “serrated” look to them. To be diagnosed these people need large polyps (two larger than 10 mm), a family history, or many polyps (more than 20). |
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Term
| Oligodontia-colorectal cancer syndrome |
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Definition
Autosomal dominant syndrome.
A various number of adenomatous polyps. Also characterised by missing adult teeth. Can also have abnormal sweating and sparse hair. |
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Term
| Lynch Syndrome (AKA Hereditary non-polyposis colorectal cancer, HNPCC) |
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Definition
Autosomal dominant. Usually MLH1 and MSH2, sometimes MSH6 or PMS2 or EPCAM.
Does have some polyps but not as many. Often early age of colorectal cancers (ie, under 45) and on the right side.
Also involved other cancers such as endometrial, ovary, stomach, urinary tract, small bowel, skin, brain, etc. Often get multiple cancers.
Look for colon and endometrial -- these are indicative of lynch syndrome.
Colonoscopies are so good colectomy is not recommended until the first cancer appears. |
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Term
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Definition
A variant of Lynch syndrome. Associated with the MSH2 and MLH1 genes.
Has dermatological features. Sebaceous gland tumors on the face and scalp and tumors from hair follicles. |
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Term
| Constitutional Mismatch Repair Deficiency (CMMR-D) |
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Definition
A brain tumor and polyposis syndrome. Features include early onset colon cancer, leukemia, childhood brain tumors, and cafe au lait macules.
Autosomal recessive. Cuased by mutations in both lynch syndrome genes (PMS2 usually). |
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