Congenital Anomalies

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Malformations

Malformations: A primary structural defect arising from a localized error in morphogenesis, resulting in the abnormal formation of a tissue or organ.

Dysplasia

Dysplasia: Refers to an abnormal organization of cells into tissues.

Malformation Sequence

Malformation sequence: A single, local tissue morphogenetic abnormality that produces a chain of subsequent defects. Example: Potter sequence (oligohydramnios, pulmonary hypoplasia, Potter facies, and joint contracture).

Malformation Syndrome

Malformation syndrome: The appearance of multiple malformations in unrelated tissues without an understandable unifying cause. Examples: DeGeorge syndrome, Down syndrome, Edward syndrome.

Deformation

Deformation: An abnormal form, shape, or position of a part of the body that results from mechanical forces. Intrauterine compression resulting from oligohydramnios can produce an equinovarus foot or clubfoot. Deformations often involve the musculoskeletal system.

Disruption

Disruption: Results from the extrinsic breakdown of, or interference with, an originally normal developmental process. Examples: Amniotic fluid bands causing amputation, interruption of blood supply causing infarction.
Deformations and disruptions are secondary effects that result from forces generated extrinsic to the affected tissue or organ.

Syndrome

Syndrome: A group of anomalies occurring together and having a specific common cause. This term indicates that a diagnosis has been made and that the risk of recurrence is known.

Association

Association: The non-random appearance of two or more anomalies occurring together more frequently, but whose cause has not been determined. Example: VACTERL (Vertebral, Anal, Cardiac, Trachea, Esophageal, Renal, and Limb abnormalities).
The most sensitive time for risks of birth defects is the embryonic period during the third to eighth weeks.
During the fetal period, the risk for gross structural defects being induced decreases, but organ systems may still be affected. For example, the brain continues to differentiate during the fetal period, such that toxic exposures may cause learning disabilities or mental retardation.

Teratogens

Teratogens: A factor that has an adverse effect on the conceptus, from fertilization till birth. The term is usually limited to environmental agents like drugs and viruses. Examples: Thalidomide, diphenylhydantoin (phenytoin), valproic acid, etc.
The most susceptible period is between the 3rd and 8th week of gestation.

Teratogens and Their Effects on the Fetus
Teratogen	Effect on Fetus
ACE inhibitors	Renal damage
Alkylating agents	Absent digits, multiple anomalies
Aminoglycosides	CN VIII toxicity
Carbamazepine	Neural tube defects, craniofacial defects, developmental delay, IUGR
Diethylstilbestrol (DES)	Vaginal clear cell adenocarcinoma, cervical cancer
Folate antagonists	Neural tube defects
Lithium	Ebstein’s anomaly (atrialized right ventricle)
Phenytoin	Fetal hydantoin syndrome: microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR, mental retardation
Tetracyclines	Discolored teeth
Thalidomide	Limb defects: amelia and meromelia (total or partial absence of extremities)
Valproate	Inhibits maternal folate absorption

Chromosomal Abnormalities

Determined at conception
Examples: Down Syndrome, Patau Syndrome, Edward Syndrome

Single Gene Defects

Usually inherited
Examples: Phenylketonuria, Tay-Sachs disease

Multifactorial Influences

Combination of genetic factors and teratogens

Mental retardation can be eliminated by supplementation of salt or water with iodine.
Placing women with diabetes and phenylketonuria under strict metabolic control prior to conception reduces the incidence of birth defects in their offspring.
Folate supplementation lowers the incidence of neural tube defects.
Avoidance of alcohol and other drugs during all stages of pregnancy.

Maternal Serum Screening

Alpha-fetoprotein (AFP)
- ↑ in amniotic fluid and maternal serum in cases of neural tube defects and several other abnormalities, including omphalocele, gastroschisis, bladder exstrophy, amniotic band syndrome, sacrococcygeal teratoma, and intestinal atresia.
- ↓ in Down syndrome, trisomy 18, sex chromosome abnormalities, and triploidy. These conditions are also associated with lower serum concentrations of human chorionic gonadotropin (hCG) and unconjugated estriol.
Amniocentesis
- AFP and acetylcholinesterase
- Fetal cells for karyotyping
Chorionic Villus Sampling
- Chorionic tissue analyzed for genetic characterization
Ultrasound
- Fetal age and growth
- Presence of gross anomalies
- Placental position
- Umbilical blood flow
- Presence of multiple gestation

Indications for Prenatal Diagnosis

Advanced maternal age (35 years and older)
Previous family history of a genetic problem, such as the parents having had a child with Down syndrome or a neural tube defect
The presence of maternal disease, such as diabetes
Abnormal ultrasound or serum screening test

Pyloric Stenosis (IHPS)

Hypertrophy and hyperplasia of muscle layers of pylorus causing functional gastric outlet obstruction
Common cause of nonbilious vomiting
More common in males, whites, and those with blood group O and B
Mothers are more likely to pass the condition to their descendants (20% to sons, 10% to daughters) than fathers
Cause remains unknown, not congenital

Clinical Manifestation

Typically presents in the 3rd week (range: 1st week – 5th month)
Nonbilious postprandial vomiting; may or may not be projectile
Baby immediately wants to feed again
Signs of dehydration, weight loss, hypochloraemic metabolic alkalosis
Normal K+

Diagnosis

Diagnosis is mainly clinical
Palpation of a firm to hard mobile mass in the mid epigastrum while baby feeds
Visible gastric peristalsis progressing from left to right after baby feeds
Ultrasound (USS): pyloric thickness >4mm, pyloric length >14mm
Barium meal: “shoulder sign”, “double tract sign”

Differential Diagnosis

Antral web
GERD
Congenital adrenal hyperplasia (salt-losing)
Sepsis
Inborn errors of metabolism
Pyloric atresia
Gastric duplication
Gastric volvulus

Treatment

Rehydrate until bicarbonate levels decrease to < 30meq/L
K+ correction as needed
Ramstedt pyloromyotomy procedure

Intestinal Obstruction

Obstruction can be complete or partial, simple or strangulating
Obstructing lesions can be intrinsic (e.g., atresia, stenosis, meconium ileus, aganglionic megacolon) or extrinsic (e.g., malrotation, constricting bands, intra-abdominal hernias, duplications)
Polyhydramnios associated with high intestinal obstruction. Gastric aspiration of 15-20ml bile-stained fluid is suggestive
Atresia refers to complete obstruction of the bowel lumen, while stenosis refers to a partial block of luminal contents
Intestinal atresia is common in the duodenum, jejunum, and ileum, and rare in the colon
Affects males and females with equal frequency

Pathophysiology

Details about pathophysiology can be elaborated here if needed

Clinical Presentation

Depends on the cause, level of obstruction, and time of presentation:

Vomiting
Abdominal distension
Obstipation

Diagnosis

History, especially prenatal ultrasound (USS)
Symptomatology
Supine, erect, or decubitus radiographs
CT Scan
Water-soluble contrast studies
FBC, blood culture, E, U & Cr

Treatment

Fluid resuscitation
Nasogastric decompression
Surgical repair

Duodenal Atresia

Thought to arise from failure to recanalize the lumen after the solid phase of intestinal development in the 4th and 5th week of gestation
Half of patients are preterm
Associated with other congenital anomalies:
- Malrotation (20%)
- Esophageal atresia (10–20%)
- Congenital heart disease (10–15%)
- Anorectal and renal anomalies (5%)
- Down syndrome (20-40%); 8% of babies with Down syndrome have duodenal atresia

Clinical Manifestation

Polyhydramnios
Bilious vomiting in the first day of life without abdominal distension

Supine frontal radiograph of the abdomen demonstrates the double bubble sign: an enlarged stomach (S) and proximal duodenum (D) in a neonate with duodenal atresia.

Hirschsprung Disease

Aganglionic Megacolon
Common form of intestinal pseudo-obstruction
Hirschsprung disease is a developmental disorder of the enteric nervous system characterized by the absence of ganglion cells in the distal colon, resulting in a functional obstruction
Should be considered in any newborn who fails to pass meconium within 24-48 hours after birth
Although contrast enema is useful in establishing the diagnosis, full-thickness rectal biopsy remains the criterion standard
Aganglionosis begins with the anus, which is always involved, and continues proximally for a variable distance
Both the myenteric (Auerbach) plexus and the submucosal (Meissner) plexus are absent, resulting in reduced bowel peristalsis and function
The precise mechanism underlying the development of Hirschsprung disease is unknown
Male:Female ratio is 4:1
At diagnosis, there is usually an enterocolitis which increases mortality
Positive family history in 10% of patients

Clinical Manifestation

Delayed passage of meconium
Chronic constipation
Abdominal distention
Poor feeding
Failure to thrive (FTT)
Diarrhea in patients with enterocolitis (10%); can progress to colonic perforation
On examination: distended abdomen, anal spasm

Diagnosis

Rectal biopsy

Treatment

PSARP: Posterior sagittal anorectoplasty

Spinal Dysraphism

Neural tube defects (NTDs) account for most congenital anomalies of the central nervous system (CNS) and result from failure of the neural tube to close spontaneously between the 3rd and 4th week of in utero development
Major neural tube defects include:
- Spina bifida occulta
- Meningocele
- Myelomeningocele
- Encephalocele
- Anencephaly
- Dermal sinus
- Tethered cord
- Syringomyelia
- Diastematomyelia
- Lipoma involving the conus medullaris and/or filum terminale

Implicated Factors

Hyperthermia
Drugs: carbamazepine, valproic acid, methotrexate
Malnutrition
Chemicals: Al, Co, agent orange
Maternal obesity or diabetes
Genetic mutations in folate-dependent pathways
Exposure of mother to radiation before conception

Review Embryology of the Neural Tube: Normally, the rostral end of the neural tube closes on the 23rd day and the caudal neuropore closes by a process of secondary neurulation by the 27th day of development, before the time that many women realize they are pregnant.

Spina Bifida Occulta

Midline defect of the vertebral bodies without protrusion of the spinal cord or meninges
Usually occurs at L5 – S1
No neurological signs in most cases
Patches of hair, a lipoma, discoloration of the skin, or a dermal sinus in the midline of the lower back suggests a more significant malformation of the spinal cord
Occasionally associated with more significant developmental abnormalities of the spinal cord, including syringomyelia, diastematomyelia, and a tethered cord. These are best identified with MRI

Spina bifida oculta

Myelomeningocele

Most severe form of dysraphism involving the vertebral column
Cause is unknown
Genetic predisposition exists; the risk of recurrence after one affected child increases to 3–4% and increases to ≈10% with two previous abnormal pregnancies
Nutritional and environmental factors play a role in etiology
Maternal periconceptional use of folic acid supplementation reduces the incidence of neural tube defects in pregnancies at risk by at least 50%
To be effective, folic acid supplementation should be initiated before conception and continued until at least the 12th week of gestation when neurulation is complete

Clinical Manifestation

Dysfunction in skin, skeleton, gastrointestinal tract (GIT), urogenital system (UGS), and peripheral nervous system
75% located at the lumbosacral region
Degree of neurological deficit depends on location:
- Low sacral: bowel and bladder incontinence, perianal anesthesia
- Mid-lumbar: cystic swelling leaking CSF, paraplegia, absent deep tendon reflexes, anesthesia, high incidence of lower extremity deformities (clubfeet, hip subluxation), bowel and bladder incontinence, neurogenic bladder
- Upper thoracic or cervical: minimal neurologic deficit and most do not have hydrocephalus
Hydrocephalus in association with a type II Chiari defect develops in at least 80% of patients

Management

In-utero surgical closure
Multidisciplinary approach
Surgery: closure + shunting procedure
Long-term management:
- Urogenital system (UGS)
- Bowel
- Physiotherapy

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