Genetic Disorder Flashcards
Both sexes are equally affected, both sexes transmit to offspring, no skipped generation, every child has a parent with disorder except new or spontaneous mutation
Autosomal dominant (AD)
Both sexes are equally affected, both sexes can transmit a copy of mutated gene, and their risk to have affected child is 25%, the disorder may be seen in one or more sibling, not all generations are affected
Autosomal recessive (AR)
No male-to-male transmission, only females transmit the disease to their sons, daughters are obligate carriers
X-linked recessive
Maternal transmission from egg to zygote; both males and females are affected
Mitochondrial inheritance
Hypotonia, upslanted palpebral fissures, epicanthal folds, systolic murmur, single transverse creases in hands, brachydactyly, broad space between the first and second toe
Down syndrome (trisomy 21)
Screening for hypothyroidism in cases of Down syndrome is at what age?
Newborn screening after birth, at 6 and 12months, then annually if normal
Acute myeloid leukemia (AML) is a higher risk in the patient with Down syndrome at what age?
Acute lymphocytic leukemia (ALL) is a higher risk in the patient with Down syndrome at what age?
> 1year
Newborn with Down syndrome with no murmur on physical examination
Echocardiography (50% of children with Down syndrome have a cardiac defect)
The most common cardiac defects associated with Down syndrome
AV canal defects, ventricular septal defect, atrial septal defect, and tetralogy of Fallot
The most common gastrointestinal defects associated with Down syndrome
Duodenal atresia, Hirschsprung disease
Newborn with clenched fist with overriding fingers, rocker bottom feet, small head, eyes, and mouth with low-set malformed ears, micrognathia, prenatal and postnatal growth deficiency, hypotonia, and ventricular septal defect
Trisomy 18 (Edward syndrome)
Newborn with cleft lip, cleft palate, microcephaly, microphthalmia, cutis aplasia, and postaxial polydactyly
Trisomy 13 (Patau syndrome)
A 5-year-old boy with intellectual disability, large hands and feet, long face with large ears, large testicles, and hyperextensible joints
Fragile X syndrome
Newborn girl with microcephaly, ocular hypertelorism, prominent glabella, frontal bossing (Greek helmet face), beaked nose, hypotonia, and seizures
Wolf–Hirschhorn syndrome (4p-deletion)
Newborn with a cat-like cry, hypotonia, microcephaly, moon face, widely-spaced eyes, down-slanting palpebral fissures, high-arched palate, and wide-flat nasal bridge
Cri du chat syndrome (5p-deletion)
Newborn with microcephaly, atresia of the ear canal, deep-set eyes, depressed mid-face, protruded mandible, legs are flexed, externally rotated, and in hyperabduction (frog-like position)
De Grouchy syndrome
Newborn with profound hypotonia, small for gestational age, feeding problems, failure to thrive, bitemporal narrowing, thin upper lip, almond- shaped eyes, hypogonadism, bilateral cryptorchidism, and small penis
Prader–Willi syndrome (PWS) (paternally derived deletion 15q11–13)
Child with hypotonia, jerky ataxic movement, fair hair, large chin and mandible, inappropriate bouts of laughter, and severe intellectual disability
Angelman syndrome (maternally derived deletion 15q11–13)
Child with an intellectual disability, supravalvar aortic stenosis, hypercalcemia, friendly “cocktail party” personality, and strabismus
Williams syndrome
The most common cause of hypercalcemia in a child with Williams syndrome
Idiopathic
Wilms tumor, Aniridia, Genitourinary malformation, Retardation (intellectual disability), long face, upward-slanting palpebral fissures, ptosis, and a beaked nose, due to the absence of PAX6 and WT1 (Wilms tumor) genes
WAGR syndrome
Newborn with Coloboma, Congenital Heart defects, choanal Atresia, growth and Retardation (intellectual disability), GU anomalies (hypogonadism), and Ear anomalies
CHARGE syndrome (gene defect CHD7 on chromosome 8q)
Vertebral defects, Anal atresia, Cardiac defects, Tracheoesophageal fistula, and/or Esophageal atresia, Renal anomalies, and Limb defects
VACTERL/VATER association
The most common association with VATER/ VACTERL syndrome
Congenital heart defects
Jaundice, bile duct paucity with cholestasis, peripheral pulmonary stenosis, butterfly vertebrae, triangular face with a pointed chin, long nose with broad mid-nose, and posterior embryotoxon
Alagille syndrome (20p12)
Cleft palate, absent thymus, hypocalcemia, tetralogy of Fallot, interrupted aortic arch, recurrent infection, short stature, and behavioral problem
DiGeorge syndrome (22q11.2)
Cleft palate, micrognathia, glossoptosis, respiratory distress (airway obstruction caused by backward displacement of the tongue base), and feeding difficulties
Pierre–Robin sequence
Pierre–Robin sequence (cleft palate, glossoptosis, and micrognathia or retrognathia); severe myopia or other ocular abnormalities; sensorineural hearing loss; or skeletal abnormalities including hypermobility, scoliosis, or early arthritis
Stickler syndrome
Newborn with a disruptive cleft on the face and amputated digits
Amniotic band sequence
Preauricular pits, preauricular tags, microtia, hypoplastic cochlea, hearing loss, branchial fistula, and renal dysplasia or aplasia
Branchio-oto-renal syndrome
Newborn with underdeveloped mandibular and zygomatic bones, microtia, stenosis of the external ear canal, down-slanting palpebral fissures, coloboma, and conductive hearing loss
Treacher-Collins syndrome (mandibulofacial dysostosis type 1)
Short stature below third percentile, short length of the proximal segment of upper arms and legs (rhizomelic shortening), trident hands, stenosis of the foramen magnum, macrocephaly, flat nasal bridge and mid-face
Achondroplasia
The most common cause of death in children younger than 4years with achondroplasia
Brain stem compression
Child, with multiple bruises, blue sclera, recurrent fractures, hyperextensible joints, and had delayed closure of fontanelle
Osteogenesis imperfecta (type I is the most common)
Adolescent, tall, the lens is dislocated upward, high-arched palate, pectus carinatum, aortic dilatation, and lumbosacral ectasia
Marfan syndrome
Adolescent with hyperextensible skin, hypermobile joints, kyphoscoliosis, easy bruising, skin scarring, mitral valve prolapse, and abnormal capillary fragility test
Ehler–Danlos syndrome
Eight café-au-lait spots, freckling of the axilla, Lisch nodules, optic glioma, and pseudarthrosis of the fibula
Neurofibromatosis type I
An 18-year-old boy with a family history of eighth cranial nerve masses presents with hearing loss, tinnitus, loss of balance, blurring of vision, and posterior subcapsular lens opacities on eye examination
Neurofibromatosis type II
Adolescent presents with facial acne that is not responding to treatment, has ash leaf (hypopigmented macules), facial angiomas (adenoma sebaceum), nail fibroma, pitting of dental enamel, and renal angiomyolipomas
Tuberous sclerosis
Infantile spasm is commonly associated with
Tuberous sclerosis
Helpful sign to assist in early diagnosis of tuberous sclerosis
Ash leaf spots (hypopigmented macules)
Most common cardiac finding in infants with tuberous sclerosis
Cardiac rhabdomyomas
Newborn with long eyelashes, hirsutism, low hairline, downward- turned mouth, intrauterine growth restriction (IUGR), thin upper lip, micromelia, and syndactyly
Cornelia De Lange syndrome
Child with partial albinism, white forelock, premature gray hair, iris heterochromia, cleft lip, and cochlear deafness
Waardenburg syndrome
Child with a history of hypoglycemia and omphalocele at birth, coarse facial features, large tongue, earlobe creases, posterior auricular pits, Wilms tumor, and cryptorchidism
Beckwith–Wiedemann syndrome
Infant with macrodactyly, hemihypertrophy, lipoma, hemangioma, soft-tissue hypertrophy, and accelerated growth
Proteus syndrome
Newborn large for gestational age, macrocephaly, prominent forehead, hypertelorism, intellectual disability, large hands and feet
Soto syndrome
Brachycephaly, frontal bossing, wormian bones, hypoplastic or absent clavicles, delayed eruption of deciduous teeth, and joint laxity
Cleidocranial dysostosis
Early fusion of sagittal suture, and the head is long and narrow
Scaphocephaly (the most common type of craniosynostosis)
Newborn with craniosynostosis, brachycephaly, strabismus, hypertelorism maxillary hypoplasia, beaked nose, proptosis, syndactyly, single nail, broad thumb
Apert syndrome
Craniosynostosis, short stature, deviated nasal septum, malocclusion, malposed teeth, no limb defects
Crouzon syndrome
Craniosynostosis, broad thumb and toes
Pfeiffer syndrome
Tower or clover-leaf skull due to multiple fused sutures, preaxial polydactyly, obesity
Carpenter syndrome
Genetic counseling requires
A specific diagnosis with known inheritance mechanism
Indications for obtaining a karyotype: examples
Unusual appearance, multiple congenital anomalies, and/or possible mental disability
Child has a routine karyotype that reveals 47, XX+21. Appropriate counseling for the parents is
To explain that their child has Down syndrome due to aneuploidy and that they do not need to have their chromosomes checked
Cytogenetic nomenclature for embryonic germ cells from a female fetus with the trisomy form of Down syndrome would be
47, XX+21
A couple desires prenatal diagnosis because the woman is 39years old. They want the safest and most reliable form of prenatal testing
Amniocentesis
Child has obesity, compulsive overeating, and underdeveloped genitalia, which make you suspect Prader–Willi syndrome. You recall that FISH testing for a chromosome 15 submicroscopic deletion may be diagnostic. The best approach for obtaining a laboratory diagnosis
Obtain a green-top (heparinized) tube for the harvest of white cells with the indication of routine karyotype, including FISH for microdeletion 15
Chorionic villus sampling is performed at which weeks of pregnancy?
10–12weeks of pregnancy
Amniocentesis is performed at which weeks of pregnancy?
12–16weeks of pregnancy
Male with tall stature, speech and language delay, learning disabilities, cystic acne in adolescence, no facial dysmorphology, normal intelligence
47, XYY syndrome
Female with tall stature; speech/language delay; learning disabilities; normal intelligence, sexual development, and fertility
47, XXX syndrome “triple X syndrome”
Male infant with short webbed neck, low posterior hairline, edema of hands and feet, mild intellectual disability mutation of PTPN11 gene
Noonan syndrome
A 10-year-old boy with progressive motor disability, cognitive decline, and psychiatric disturbances; his father had the same condition at age 40years, died at age of 60
Juvenile Huntington disease (because of CAG trinucleotide repeat expansion, clinical onset can occur in childhood) AD
