CONGENITAL MALFORMATIONS
Congenital malformations are defined as “anatomical or structural defects, present at birth, with/without functional impairment.quot; Although used interchangeably, the term congenital anomaly has wider connotation, i.e.
structural, functional, biochemical or physiological disorders of prenatal origin.Structural malformations may be broadly divided into major malformations with significant functional impairment, e.g. CHDs or neural tube defects; and minor malformations without direct functional implications, e.g. pre-auricular skin tags.
Incidence: Congenital malformations are third commonest cause of perinatal mortality in India, estimated to be present in ~2.5% of newborns at birth and incidence may rise to 4-5% by 5 years, as many defects manifest in later life.
Etiology: Over 60% of congenital malformations are idiopathic, rest due to various intrinsic (genetic) defects or extrinsic (environmental) factors (Table 12.59). Term teratogens is applied to those environmental influences, which are known to have definite exposure-risk relationship with a congenital anomaly, e.g. maternal infections, drugs, radiation and alcohol/ smoking. Only 10% malformations are due to recognizable teratogens. Classification: Congenital malformations may be single primary defects or multiple malformation syndromes.
TABLE 12.59: Common causes of congenital malformations
• Idiopathic (~60%)
• Intrinsic or inherited (~ 25-30%)
- Chromosomal: Down syndrome, Turner syndrome
- Single gene: Achondroplasia, Holt-Oram syndrome
- Polygenic: Cleft palate, neural tube defects, CHDs
• Extrinsic or environmental (~10-15%)
- Maternal infections: Rubella, CMV, toxoplasmosis
- Maternal diseases: Diabetes, iodine deficiency
- Drugs/toxins: Antiepileptics, alcohol, hormones
- Maternal smoking, irradiation
- Maternal malnutrition, e.g.
folic acid deficiency- Uterine anomalies or oligohydramnios
Depending on the etiology and secondary effects, various terms are used to denote these defects, as follows:
• Malformation, i.e. a single morphological defect due to intrinsic error in embryogenesis and organ differentiation, e.g. cleft lip or CHD.
• Deformation, i.e. abnormal shape/position of normally-formed body part due to abnormal uterine pressure/posture, e.g. congenital dislocation of hip or congenital talipes equinovarus. Abnormal posture may be due to extrinsic uterine pressure, e.g. oligohydramnios, or intrinsic fetal hypotonia, e.g. neuromuscular disorders.
• Disruption, i.e. destruction of a normally-formed body part in late gestation, due to: (a) tearing/ amputation of a structure by floating strands of amnion, e.g. amniotic band syndrome, loss of a digit or limb, etc.; or (b) interruption of blood supply due to infection, trauma or other teratogens, leading to distal infarct, necrosis or resorption, e.g. intestinal atresia, porencephaly, etc.
• Dysplasia denotes abnormal organization of constituent cells in a structure, leading to abnormal growth. Dysplasias may be localized, e.g. hemangioma, or generalized, e.g. skeletal dysplasia. Being growthdependent, clinical appearance in these defects tend to change with age, e.g. hemangiomas may regress or skeletal dysplasias may deteriorate, postnatally.
• Sequence denotes a spectrum of multiple malformations due to cascading effect of a single primary defect in morphogenesis. Depending on the primary error, a sequence is further classified as malformation, deformation or disruption sequence. Some common sequences include:
- Robin malformation sequence, with primary defect of mandibular hypoplasia, leading to macroglossia, glossoptosis and high-arched palate.
- Breech deformation sequence due to abnormal uterine pressure in breech position, leading to abnormal skull shape, facial asymmetry, torticollis, CDH and CTEV.
Similar abnormalities are also seen Potter's sequence, due to oligohydramnios.- Amniotic band disruption sequence, due to disruption of normally formed amniotic membrane, leading to defects, e.g. cleft lip, limb defects, aplasia cutis, etc. Sequences need to be differentiated from multiple malformation syndrome, as the recurrence risk in them depends on the primary defect.
• Multiple malformation syndrome denotes presence of one or more development abnormality involving at least two different systems, due to an established cause. Most of these defects are chromosomal or polygenic in origin, e.g. Down syndrome, though others may be due to single gene defects or environmental factors, e.g. intrauterine exposure to
TABLE 12.60: Diagnostic clues for congenital malformations
History
• Family history of malformed parents/sibling
• Parental consanguinity
• Elderly mother or father
• Teratogens: Infections, drugs, alcohol
• Maternal diseases, e.g. diabetes
• Oligo-/poly-hydramnios
• Abnormal fetal movements/presentation
Clinical examination
• External appearance
• Patency test/orifice count at birth
• Single umbilical artery
• Stigmata, e.g. spinal hair tuft, auricular tags
• Systemic examination, e.g. CHDs
infection/drugs (congenital rubella syndrome, fetal hydantoin syndrome, etc.).
• Association denotes a non-random (more than by chance) occurrence of multiple malformations in a combination, not explained by a common etiological basis, i.e. syndrome or sequence. Two common associations are:
- VATER association (Vertebral anomalies, Anal atresia, Tracheoesophageal fistula, Esophageal atresia and Renal/Radial defects).
- CHARGE association (Coloboma, Heart disease, Choanal Atresia, growth/mental Retardation with/ without CNS anomalies, hypoGonadism and Ear anomalies or deafness.
Diagnosis: Although most congenital malformations are obvious at birth, some may be easily missed in early life. Early diagnosis of major malformations is essential for survival, appropriate management and prevention of late complications.
Important clinical clues about presence of a congenital malformation or etiological diagnosis are given in Table 12.60, though confirmation may require relevant investigations. Genetic studies are indicated in select cases with intrinsic cause of malformation, to assess the risk of recurrence and prenatal diagnosis. Diagnosis and management of individual congenital malformations has been discussed in related chapters.BIBLIOGRAPHY
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