Congenital anomalies

Question 1

What is CHARGE syndrome?

Answer 1

• mutation usually of CHD7 gene
• Coloboma of the eye – hole in one of the structures of eye.
• Heart defects – vary in severity, but can include ventricular septal defects and tetralogy of Fallot.
• Atresia of the choanae – one or both of the openings at the back of the nose are blocked by bone or tissue. Choanal atresia causes breathing difficulties.
• Retardation of growth and/or development – children with CHARGE syndrome may not grow and develop at the same rate as other children their age. Often, they do not start puberty without additional hormone treatment.
• Genital and/or urinary abnormalities – small penis and/or undescended testicles. The inner lips of the vagina may be very small.
• Ear abnormalities and deafness – most children with CHARGE syndrome have some level of hearing impairment, varying from mild to profound, along with underdeveloped or low-set ears.

Question 2

Patau syndrome (trisomy 13)

Answer 2

• most affected babies die in infancy
• most detected on antenatal USS (2nd tri) followed by chromosomal analysis
• Clinical features
  
  • _​_structural defect of brain
  • scalp defects
  • microphthalmia
  • other eye defects
  • cleft lip and palate
  • polydactaly
  • cardiac and renal malformations

Question 3

Edwards syndrome (trisomy 18)

Answer 3

• Clinical features
  
  • _​_LBW
  • prominent occiput
  • small mouth and chin
  • short sternum
  • flexed, overlapping fingers
  • ‘Rocker-bottom’ feet
  • cardiac and renal malformations

Question 4

NTDs

Answer 4

Cause: failure of fusion of neural plate to form the neural tube during first 28 days of conception. Folic acid supplementation = reduction in risk.

• high dose- those with previous NTD pregnancy periconceptually
• low dose- all pregnancies periconceptually

Anencephaly: failure of development of most of cranium. Still birth or die within hours of birth. Usually detected antenatally on USS - termination usually performed.

Encephalocele: extrusion of brain and meninges through a midline skull defect. Corrected surgically. Underlying cerebral malformations.

Spina bifida occulta: failure of fusion of vertebral arch. Incidental finding on XR or skin lesion: tuft of hair, lipoma, birth mark or small dermal sinus. Tethering of cord may be underlying.

Meningocele: good prognosis after surgical repiar.

Myelomeningocele: associated with variable paralysis of legs; muslce imbalance (may cause dislocation of hip/ talipes), sensory loss, bladder denervation (neuropathic bladder), bowel denevervation (neuropathic bowel), scoliosis, hydrocephalus (Chiari malformation)

Question 5

Features of ambiguous genitalia and management

Answer 5

• Y chromosome presence –> differentiation of gonad into a testis (production of testosterone and dihydrotestosterone result in development of male genitalia)
• Absence of Y–> gonads become ovaries and the genitalia female
• Most common cause of a disorder of sexual development is female virilisation from congenital adrenal hypoplasia
• Features:
  
  • ​abnormal genitalia- half way between male and female
• Management
  
  • ​if genitalia is abnormal infant sex must not be assigned
  • medical, surgical, psychological specialist involvement
  • birth registration delayed
  • karyotyping
  • adrenal and sex hormone measurements
  • USS of internal structures and gonads
  • females: corrective surgery within 1st year of life- definitive usually delayed until puberty
  • males (salt-losing): saline, dextrose, hydrocortisone IV
  • both (long-term): lifelong glucocorticoids, mineralocortoids (salt loss), monitoring of growth, skeletal maturity, plasma androgens and 17AH
  • additional hormone replacement during illness/ surgery (unable to mount a cortisol response)

Question 6

What is congenital adrenal hypoplasia?

Answer 6

• Autosomal recessive condition- disorder of adrenal steroid biosynthesis
  
  • 90% = deficiency of 21-hydroxylase (cortisol production)
  • 80% = loss of aldosterone leading to salt loss
  • Decrease in corticol stimulates pituitary to release adrenocorticotrophic hormone (ACTH) which drive the overproduction of adrenal androgens
• Features:
  
  • ​virilization in female infants: clitoral hypertrophy, fusion of labia
  • enlargement/ pigmentation of penis in males
  • 80% males = salt losers
    
    • 1-3 weeks of age
    • vomiting, weight loss, floppiness and circulatory collapse
  • 20% males = non-salt losers
    
    • tall stature
    • muscular build
    • adult BO
    • pubic hair
    • acne
    • precocious pubarche
• Diagnosis
  
  • _​_increased 17-alpha-hydroxyprogesterone
  • hyponatraemia
  • hyperkalaemia
  • metabolic acidosis
  • hypoglycaemia

Question 7

Inborn errors of metabolism associated with ambiguous genitalia

Answer 7

• androgen insensitivity syndrome
• 5-alpha reductase deficiency
• gonadotrophin insufficiency (Prader-Willi, congenital hypopituitarism)
• ovotesticular disorder of sexual development- hermaphroditism
  
  • ​rare
  • complex external phenotype
  • XX- and Y- containing cells

Question 8

Outline impact of renal abnormalities on developing fetus and newborn

Answer 8

• abnormalities identified in 1/ 200-400 births
• abnormal renal development and function
• predispose to postnatal infection
• urinary obstruction- requiring surgical intervention
• Abnormalities detectable on antenatal USS
  
  • _​_renal agenesis
    
    • severe oligohydramnios
    • results in Potter syndrome
  • multicystic dysplastic kidney (MDK)
    
    • failure of union of uteric bud with the nephrogenic mesenchyme
    • non-functioning structure
    • no renal tissue
    • no connection to bladder
    • 50% involute by 2 years of age
    • nephrectomy: HTN, large defect
    • Potter syndrome results if bilateral
  • autosomal recessive polysystic kidney
    
    • ​some/normal renal function
    • both kindeys affected
  • autosomal dominant polycystic kidney
    
    • ​some/normal renal function
    • both kindeys affected
    • HTN
    • haematuria
    • RF in late adulthood
    • cysts in liver/ pancreas/ cerebral aneurysms MV prolapse
• Potters syndrome: intrauterine compression of fetus from oligohydramnios caused by lack of fetal urine.
  
  • characteristic facies
  • lung hypoplasia
  • postural deformities (severe talipes)
  • still born
  • respiratory failure after birth (hrs)
• Other renal abnormalities
  
  • _​_pelvic/ horseshoe kidney
  • duplex system
  • bladder exotrophy
  • Prune-belly syndrome
    
    • absence of or severe deficiency of abdo wall mm, large bladder, dilated ureters and crytorchidism
  • obstruction in renal tract
  • neuropathic bladder
  • posterior urthethra
  • posterior urethral valves

NB poor liquor growth volume results in pulmonry hypoplasia. Newborn kidney has low GFR, low urine flow therefore may not present for a few days