Review – Kaplan Pediatrics: Genetic / Dysmorphology

Dec 4, 2019 admin NHI KHOA 0

Review – Kaplan Pediatrics: Genetic / Dysmorphology

Trisomy 21 (Down Syndrome)

  • 94% full trisomy 21(nondisjunction); 4–6% with translocation
  • Findings
    • Upward slanting palpebral fissures; speckling of iris (Brushfield spots); inner epicanthal folds
    • Small stature, mouth open with tongue protrusion; mild microcephaly, short neck, flat occiput, short metacarpals and phalanges; single palmar crease
    • Hypotonia
    • Hearing loss (sensorineural, conductive, and mixed)
    • Primary gonadal deficiency
    • Cardiac anomaly—ECD > VSD > PDA, ASD; also MVP
    • Gastrointestinal anomalies: duodenal atresia, Hirschprung
    • Atlanto-axial instability
    • Hypothyroidism
    • Acute lymphocytic leukemia
    • Mental retardation, variable

ASD: atrial septal defect; ECD: endocardial cushion defect; MVP: mitral valve prolapse; PDA: patent ductus arteriosus; TOF: tetralogy of Fallot; VSD: ventricular septal defect

Trisomy 18 (Edwards Syndrome)

  • Mental retardation
  • Low-set, malformed ears; microcephaly, micrognathia; prominent occiput
  • Clenched hand—index over third; fifth over fourth
  • Short sternum
  • VSD, ASD, PDA, cyanotic lesions
  • Rocker-bottom feet, hammer toe
  • Omphalocele

Trisomy 13 (Patau Syndrome)

  • Holoprosencephaly and other CNS defects
  • Severe mental retardation
  • Microcephaly; microphthalmia
  • Severe cleft lip, palate, or both
  • Scalp defects in parietal-occipital area (cutis aplasia)
  • Postaxial polydactyly
  • VSD, PDA, ASD, cyanotic lesions
  • Single umbilical artery

Aniridia–Wilms Tumor Association (WAGR syndrome)

  • WAGR syndrome: deletion of 11p13; Wilms + aniridia + GU anomalies + MR

Klinefelter Syndrome (XXY)

  • Genetics; most common findings manifested at puberty
  • Mental retardation (average IQ 85-90)
  • Long limbs (decreased upper:lower segment ratio); arm span > height
  • Slim (weight/height ratio low)
  • Hypogonadism and hypogenitalism (testosterone replacement at 11-12 years of age) = hypergonadotrophic hypogonadism (increased FSH and LH, and decreased testosterone)
  • Gynecomastia

Turner Syndrome (XO)

  • Small-stature female
  • Gonadal dysgenesis–streak ovaries in XO
  • Average IQ 90
  • Congenital lymphedema, residual puffiness over dorsum of fingers and toes
  • Broad chest, wide-spaced nipples
  • Low posterior hairline; webbed posterior neck
  • Cubitus valgus (elbow) and other joint problems
  • Horseshoe kidney, and other renal defects
  • Cardiac:
    • Bicuspid aortic valve (number 1 cardiac anomaly)
    • Coarctation
    • Aortic stenosis, mitral valve prolapse
    • Hypertension common, even without cardiac or renal disease
  • Primary hypothyroidism, mostly autoimmune, and other autoimmune diseases (celiac disease)
  • May increase height by 3–4 cm with growth hormone (GH) and anabolic steroids

 Fragile X Syndrome

  • Fragile site on long arm of X
  • X-linked dominant
  • Mild to profound mental retardation; learning problems
  • Large ears, dysmorphic facial features, large jaw, long face
  • Large testes—mostly in puberty (macroorchidism)

Beckwith-Wiedemann Syndrome

  • Macrosomia
  • Macroglossia—may need partial glossectomy
  • Pancreatic beta cell hyperplasia—excess islets → hypoglycemia; hypoglycemia may be refractory; glucose control most important initial management
  • Umbilical abnormalities, diastasis recti, omphalocele
  • Hemihypertrophy → increased risk of abdominal tumors (Wilms)
  • Management—obtain ultrasounds and serum AFP every 6 months through 6 years of age to look for Wilms tumor and hepatoblastoma

Prader-Willi Syndrome

  • Paternal chromosome responsible
  • Obesity—onset from 6 months to 6 years
  • Mild to severe mental retardation
  • Food-related behavioral problems (binge eating)
  • Small hands and feet, puffy; small genitalia
  • Hypothalamic—pituitary dysfunction (growth, thyroid, adrenal) hypogonadotrophic-hypogonadism

Angelman Syndrome (Happy Puppet Syndrome)

  • Severe MR
  • Paroxysms of inappropriate laughter
  • Absent speech or <6 words (100%); most can communicate with sign language
  • Ataxia and jerky arm movements resembling a puppet’s movements (100%)

Robin Sequence (Pierre Robin)

  • Micrognathia
  • Retroglossia → possible airway obstruction
  • Cleft soft palate and other abnormalities

Achondroplasia/Hypochondroplasia

  • Short stature (increased upper-to-lower segment ratio; short-limbed dwarfism)
  • Proximal femur shortening
  • Megalocephaly, small foramen magnum (may have hydrocephalus), small cranial base, prominent forehead
  • Lumbar lordosis

Marfan Syndrome

  • Tall stature with long, slim limbs and little fat
  • Arachnodactyly
  • Joint laxity with kyphoscoliosis

Ehlers-Danlos Syndrome

  • Droopy ears
  • Hyperextensible skin, fragile, easy bruisability, poor wound healing
  • Joint hyperlaxity; tendency toward hip, shoulder, knee, and clavicular dislocation
  • MVP, tricuspid valve prolapse, aortic root dilatation; dissecting aneurysm, ASD
  • Blue sclera, myopia, glaucoma, ectopia lentis, retinal detachment
  • Intracranial aneurysm

Fetal Alcohol Syndrome (FAS)

  • Alcohol—most common teratogen to which fetus can be exposed
  • Findings—variable
  • Pre- (symmetric IUGR) and postnatal growth deficiency (short stature)
  • Mental retardation, microcephaly
  • Fine motor dysfunction
  • Irritability in infancy, hyperactivity in childhood
  • Behavioral abnormalities
  • Mid-face dysmorphism (abnormal frontal lobe development), short palpebral fissures, maxillary hypoplasia, short nose, smooth philtrum, thin and smooth upper lip
  • Joint abnormalities—abnormal position and/or function
  • Cardiac anomalies: VSD > ASD, tetralogy of Fallot

Fetal hydantoin syndrome

  • Similar features with prenatal exposure to carbamazepine, valproate, primidone, and phenobarbital
  • No dose-response relationship has been
  • Growth deficiency
  • Borderline to mild mental retardation
  • Dysmorphic facial features; short neck; abnormal palmar crease
  • Rib abnormalities
  • •      Hirsutism
  • Cupid’s-bow lips

 Fetal valproate syndrome

  • Midface hypoplasia; cleft lip
  • Cardiac defects
  • Long, thin fingers and toes; convex nails
  • Meningomyelocele

Retinoic acid embryopathy (from isotretinoin)

  • Mild facial asymmetry; bilateral microtia/anotia (ear); facial nerve paralysis ipsilat- eral to ear; narrow, sloping forehead; abnormal mottling of teeth
  • Conotruncal malformations
  • CNS malformations
  • Decreased intelligence
  • Thymic and parathyroid abnormalities
  • No problems if stopped before 15th postmenstrual day
  • Pregnancy test required prior to treatment with isotretinoin

Potter Sequence

  • Renal agenesis/dysgenesis or other type of urinary tract defect must occur prior to 31 days’ gestation → oligohydramnios (also from chronic leakage)
    • Leads to fetal compression (mid-face, ears)
    • Lack of alveolar sac development → pulmonary hypoplasia
  • Pulmonary hypoplasia
  • Potter facies—hypertelorism, epicanthal folds, low-set flattened ears, microgna- thia, compressed flat nose

VACTERL Association

Nonrandom association of

  • V = Vertebral defects
  • A = Anal atresia (imperforate anus)
  • C = Cardiac defects (VSD and others)
  • T = TE fistula
  • E = Esophageal atresia
  • R = Renal defects
  • L = Limb defects (radial)

CHARGE Association

Nonrandom association of

  • C = Coloboma (from isolated iris to anophthalmos; retinal most common)
  • H = Heart defects (TOF, PDA, and others)
  • A = Atresia choanae
  • R = Retardation of growth and/or development
  • G = Genital hypoplasia (in males)
  • E = Ear anomalies and/or deafness

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