This page graphs gives a breakdown of the Australian statistics of major developmental abnormalities grouped by systems.
The main objective in using Spina Bifida as a teaching model is to stress the main features in an integrated approach to the total care of the Spina Bifida patient.
See also the NHMRC Publication Dietry Folic Acid and Neural Tube Defects
Questions related to Spina Bifida
(a) Describe the possible processes involved in the abnormal development of the C.N.S. in Spina Bifida. At what time in development would these abnormal events occur?
(b) What is amniocentesis? Would this procedure be useful in the diagnosis of Spina Bifida? Give reasons for your answer.
(c) What is the effect of the lesion on the bladder, bowel and limbs? Describe the differences on these areas between lesions at the following levels:
(d) If the lesion is at higher thoracic levels, why would the prognosis for the patient be poor?
The malformations CLEFT LIP and palate and PIERRE ROBIN SYNDROME during the lecture series and demonstration materials will be provided during the practical class.
Cleft lip and palate develop between the 4th and 8th week of gestation and is dominated by changes resulting in the formation of the nose. Palatal development occurs between the 7th and 12th week of gestation and is divided into the formation of the primary palate (prolabium), premaxilla and cartilaginous septum) and formation of the secondary palate (hard and soft palate).
In the treatment and repair of cleft lip the following results are hopefully achieved:
(i) a symmetrical lip
(ii) a natural appearing philtral ridge and dimple
(iii) negligible scarring
(iv) a symmetrical nose and restoration of the nostril floor.
The major objectives of the repair of the cleft palate includes construction of a competent, functioning and watertight valve at the junction of the soft palate and pharynx; repair is performed early enough to allow the child to begin speech with a functioning velopharyngeal valve. Presentation of normal hearing must also be maintained along with normal development and bone growth in the central facial region along with a functional and attractive dentition.
Treatment. PDA is ligated simply and with little risk. The operation is always recommended even in the absence of cardiac failure. It can often be deferred until early childhood.
Treatment The surgical repair requires a cardiopulmonary bypass and is recommended in most cases of ostium secundum ASD, even though there is a significant risk involved. Ostium primum defects tend to present earlier and are often associated with endocardial cushion defects and defective mitral or tricuspid valves. In such cases, valve replacement may be necessary and the extended operation has a considerable chance of mortality.
Congenital Malformations Australia 1981-1992 P. Lancaster and E. Pedisich ISSN 1321-8352
Characterized by aorta arising from right ventricle and pulmonary artery from the left ventricle
Congenital Malformations Australia 1981-1992 P. Lancaster and E. Pedisich ISSN 1321-8352
Characterized by obstructive valvular and vascular lesion of the left side of the heart.
Congenital Malformations Australia 1981-1992 P. Lancaster and E. Pedisich ISSN 1321-8352
OESOPHAGEAL ATRESIA- with or without tracheo-oesophageal fistula
Oesophageal atresia as suggested by
(b) Reflex increase in salivation
(c) Holdup of the catheter confirmed by the X-ray appearance of the dilated blind proximal oesophagus. The fistula is confirmed by the presence of gas in the intestines.
1. Operative closure of the trachea end of the fistula.
2. Restoration of the continuity of the oesophagus
N.B. This is a serious malformation with significant risk of mortality
(a) Stratified squamous epithelium and columnar epithelia (mixtures of tracheal and oesophageal epithelial) are found in the trachea and oesophagus.
(b) This often occurs as one of a complex of malformations in a child. The origin is in early embryogenesis and often associated with
(i) cloacal malformation
(ii) cardiac septal defects
(iii) renal malformations
(a) The failure of what embryological process might give rise to this malformation?
(b) Why is there almost invariable association of tracheo oesophageal fistula with polyhydramnios?
(c) Why is there an early onset of pneumonia if the malformation is unrecognised?
(d) How might the defect possibly be corrected?
OMIM Database Entry- Lobar Emphysema
1. There is an overinflated left upper lobe
2. There is a collapsed lower lobe
3. The left lung is herniating across the mediastinum
Description of lesion - there is a congenital deficiency of cartilage in the left upper lobe bronchus. The anatomical nature of the lesion was demonstrated by autopsy specimens and usually reveals no abnormality other than cartilage deficiency throughout the lobe.
(a) Respiration is normal at first
(b) Once distress occurs overinflation is rapidly progressive and may kill by asphyxia.
(c) This is called Lobar Emphysema due to congenital broncho-malacia (soft bronchi).
The affected lobe must be resected.
1. R.D.S. is normally treated conservatively with 02, intravenous bicarbonate and general supportive measures but the mortality rate is high in more premature infants. At autopsy the principle change to be seen is an eosinophilic hyaline membrane filling the alveoli.
2. If the child is treated with constant positive airway pressure this increases arterial 02 tension and helps prevent the collapse of alveoli which deficient surfactant otherwise causes. This increases the functional residual capacity of the lungs. This support system is effective in the nearly mature infants but the more premature still have a high mortality rate.
Failure of the pleuroperitoneal foramen (foramen of Bochdalek) to close allows viscera into thorax. Intestine, stomach or spleen can enter the pleural cavity, compressing the lung.
Common condition (0.5% of population). The right lung upper lobe expands either side of the posterior cardinal.
Condition is generally harmless.
I. INTESTINAL MALROTATION
What abnormal embryological processes could interfere with normal rotation and fixation of the gut?
II. SITUS INVERSUS VISCERA
Disturbance of the lateralisation of the liver may produce transposition of some or all of the foregut and its derivatives.
3. Duodenum - jejunum
Also in situs inversus the anatomical relations of the duodenum, pancreas, bile ducts and portal veins may be reversed or disordered.
OMIM Database Entry- Situs Invertus (about this entry)
III. MECKEL'S DIVERTICULUM
OMIM Database Entry- Meckel's Diverticulum (about this entry)
IV. HIRSCHSPRUNG'S DISEASE (INTESTINAL AGANGLIONOSIS)
V. GASTROINTESTINAL ABNORMALITIES, MULTIPLE
Note that upper G.I.T. obstruction is associated with POLYHYDRAMNIOS whereas failure of fetal micturition is associated with OLIGOHYDRAMNIOS with consequent firm uterine moulding on the fetus, leading to facial, locomotor and palatal deformities. The "figures" referred to below are on posters in the practical classroom.
(a) In the complete form the child is not viable and the child dies within a few days of birth.
(b) Features associated with this anomaly are:-
(ii) Amnion nodosum (small warty amnion with accretions of squamous cells on the inner wall). This is tangible evidence for oligohydramnios.
(iii) Facial deformities: This results from uterine moulding around the head.
(Figure 1). The ears are low slung and simple, the mandible is small, the nose flattened and the eyes exhibit Pre-epicanthic folds (Figure 2). This is a horseshoe shaped flap of skin from the upper lid to the cheek in front of the epicanthus. (Downs syndrome has an epicanthic fold). Note that the genesis is occasionally incomplete allowing survival (e.g.) Figure 2. Causal factors are largely unknown although there is some familial predisposition.
This is a diffuse cystic malformation of both kidneys with cystic malformations of the liver and lung etc. often being associated. There is often familial disposition with this malformation. There are TWO types
(i) Infantile (inconsistent with prolonged survival)
(ii) Adult (less severe and allows survival)
(i) This is non familial and is produced by atresia of a ureter
(ii) It is always unilateral
(iii) There is no functional kidney tissue present in the kidney
(iv) The kidney is replaced by a multiocular cyst.
1. (e.g.) Urethral valves (Figure 9) - This figure is a micturating urethrogram and shows a valve obstruction (arrow) with dilatation of the urethra between the valve and the bladder. This type of pre-natal obstruction produces gross hydronephrosis and hydroureter before birth. Figure 10 shows gross dilatation of the pelves and ureters. There is extensive destruction of renal tissue.
2. Congenital Hydronephrosis is usually due to partial obstruction at the pelvi-ureteric junction (Figure 11). The pelvis is shown to be grossly dilated and there is extensive renal damage before birth.
*This may be familial, may be lateral, and is most commonly an intrinsic defect in the wall of the ureter (structural or functional). The less severe cases may be salvaged by reconstruction of the pelvi-ureteric junction.
The Triad is
(i) Agenesis of abdominal wall muscles
(ii) Bladder outflow obstruction
(iii) Bilateral undescended testes
*The causes of this malformation are little known, but maternal therapy with Oestrogens in the first trimester has been implicated frequently.
Question: Does oestrogen possibly inhibit the development of the male bladder outflow and genital system?
In some cases there are vestiges of muscle in the abdominal wall and it is not known whether this represents
(a) destruction of muscle, or (b) failure of development of muscle
Figures 12 and 13 show a typical prune belly.
Survival of the prune belly child depends on the number of functioning remaining nephrons at birth and the operability of the obstruction.
In the horseshoe kidney there is fusion of the lower poles of the kidney.During migration from the sacral region the two metanephric blastemas can come into contact as shown in Figure 14 mainly at the lower pole. The ureters pass in front of the zone of fusion of the kidneys. The kidneys and ureters usually function adequately but there is an increased incidence of upper urinary tract obstruction or infection.
Management of Bladder Exstrophy
The deformity is non-familial, of no known cause and is obvious at birth. This malformation produced incontinence. The surgical reconstruction is complex and requires simultaneous repair of the bony pelvis and covering of the bladder and bladder neck. The epispadiac urethra is reconstructed later. (Ref. Snell, Clinical Embryology, p. 215, fig. 15-16).
1. Normal growth and development of the limb requires (a) normal cell numbers; (b) normal locomotor elements, e.g. bone, joint, muscle; (c) normal blood and nerve supply.
2. Retardation of limb growth is produced by (a) deficient nerve supply; (b) impaired blood supply or (c) systemic abnormalities affecting the growth plate.
3. Increased limb growth is produced by some nerve malformations and by increased blood supply to the growth plate.
The "figures" referred to below are on posters in the practical classroom.
Introduction (Instability: 1:60 at birth; 1:240 at 1 wk: Dislocation untreated; 1:700).
(a) There is originally a congenital instability of the hip which later dislocates by muscle pulls or gravity if untreated.
(b) There is familial predisposition for this problem and female predominance.
(c) Growth of the femoral head, acetabulum and innominate bone are delayed until the femoral head fits firmly into the acetabulum.
Mechanisms of Production
(a) There is familial displasia of the hip.
(b) There is a relationship between placental transmission of material joint softening hormones (e.g. Relaxin) which are inhibited by androgens in the male foetus. When a and b are present there is instability of the hip.
(c) Dislocation is produced by the small head slipping out of the shallow acetabulum in the extended position of the hip and is inhibited by the abducted position of the hip.
Treatment must be instituted early to avoid a growth deformity of the hip. To ensure there is no instability, infants are tested at birth for hip stability and unstable hip children are nursed in the Frog Position (abducted hip posture).
Photo CDH1 Pawich Brace
Photo CDH2 Frog Plaster
Delay in treatment leads to frank dislocation of the hip (the femoral head comes out of joint), and there is a shallow acetabulum and a small femoral head. See Photo CDH3. If this condition is allowed to occur an operation may be necessary to produce a more horizontal roof to the acetabulum and produce hip stability. See Photo CDH4.
Posterior dislocation of the hip produces flexion deformities of the hip with compensatory Lordosis - exaggerated lumbar curvature. See Photo CDH5 (both female).
1. In CDH5 the smaller child on the right shows Trendelenberg's Sign - as she raises her right foot the right side of the pelvis lowers instead of raising. In the normal patient the hip rises when the ipsilateral foot is raised from the ground. What muscle is chiefly responsible for the normal tilting of the hip?
2. What conditions may give rise to Trendelenberg's Sign?
Severe cases are characterised by multiple deformities at birth with gross stiffening of joints and hypotonia or wasting of muscles.
Photo AG1. Such a stiff fetus frequently sustains fractures before or during delivery. AG1 has had a fractured right humerus.
Photo AG2 shows deformities originally thought to be joints, then joints and muscles then finally innervation was also implicated.
Photo AG3 shows normal and abnormal muscles in close proximity. Variations in the degree of severity of joint deformity are expressions of varying degrees of muscular and neurological abnormality.
Fusion of fingers or toes. This may be single or multiple and may affect
(i) Skin only
(ii) Skin and soft tissues
(iii) Skin, soft tissues and bone
See Knock out Mouse Reference
The condition is unimportant in toes but disabling in fingers and requires operative separation. This is frequently inherited as an autosomal dominant. Photo
OMIM Database Entry- Syndactyly I
OMIM Database Entry- Syndactyly II
OMIM Database Entry- Syndactyly III
OMIM Database Entry- Syndactyly IV
OMIM Database Entry- Syndactyly V
Database Entries- Syndactyly List
This is involved with assymetric growth impairment of the
vertebral bodies. There is lateral deviation of the spine
with a 3-fold deformity: Photos: Sco 1: Shows Scoliosis Sco 2: Rotational deformity producing rib hump when the
child bends Sco 3: X-ray of spine The deformity is compensated by movement of the vertebral
column above and below the affected region producing a
primary and two secondary curves. This deformity progresses
rapidly in adolescence and becomes fixed once bone growth is
completed. Questions Why does the deformity progress rapidly in early
adolescence? Thalilomide was the most celebrated limb reducing insult
in humans which produced other deformities as well. There
was probably a primary neuronal deprivation. There are two
elements in the production of limb reduction defects. (b) Mechanisms - Limb reduction defects may be due to
loss of blood supply to part of the limb or to defects in
innervation at the spinal or cerebral level. Also there
are a number of as yet undefined mechanisms involved. Limb reduction defects may be apical (congenital
amputation) or pre- or post-axial (absence of radius and
lateral digits; ulnar and medial digits). Photo LRD 1 and 2 shows a limb reduction defect and the
accompanying X-ray. Questions What area is missing in the reduced limb? What will be the relative growth rates of the right and
left humeri in this child? Other examples of limb reduction defects are shown by
:- Photos: LRD 3:A reduction defect, largely preaxial
hemimelia LRD 4: An apical defect LRD 5: A severe apical defect, the lobster claw foot. Question What problems would a patient with the lobster-claw foot
defect encounter when walking? Self Assessment Questions What are the major causes and consequences of congenital
dislocation of the hip and scoliosis?
(a) Agents - Many substances have been found
capable of producing limb reduction defects in
experimental animals but few have been related to humans.
This is involved with assymetric growth impairment of the vertebral bodies. There is lateral deviation of the spine with a 3-fold deformity:
Sco 1: Shows Scoliosis
Sco 2: Rotational deformity producing rib hump when the child bends
Sco 3: X-ray of spine
The deformity is compensated by movement of the vertebral column above and below the affected region producing a primary and two secondary curves. This deformity progresses rapidly in adolescence and becomes fixed once bone growth is completed.
Why does the deformity progress rapidly in early adolescence?
Thalilomide was the most celebrated limb reducing insult in humans which produced other deformities as well. There was probably a primary neuronal deprivation. There are two elements in the production of limb reduction defects.
(b) Mechanisms - Limb reduction defects may be due to loss of blood supply to part of the limb or to defects in innervation at the spinal or cerebral level. Also there are a number of as yet undefined mechanisms involved.
Limb reduction defects may be apical (congenital amputation) or pre- or post-axial (absence of radius and lateral digits; ulnar and medial digits).
Photo LRD 1 and 2 shows a limb reduction defect and the accompanying X-ray.
What area is missing in the reduced limb?
What will be the relative growth rates of the right and left humeri in this child?
Other examples of limb reduction defects are shown by :-
Photos: LRD 3:A reduction defect, largely preaxial hemimelia
LRD 4: An apical defect
LRD 5: A severe apical defect, the lobster claw foot.
What problems would a patient with the lobster-claw foot defect encounter when walking?
Self Assessment Questions
What are the major causes and consequences of congenital dislocation of the hip and scoliosis?
Relate to lifestyle, environment and nutrition. Some examples of this form of abnormality are the impact of excess alcohol on neural development (Fetal alcohol syndrome), viral infection (rubella) at a critical stage of development, inadequate dietry folate intake (neural tube defects), effects of prescription drugs (Thalidomide- limb development) and even maternal endocrine function (thyroid development).
In addition to these obvious maternally-derived abnormalities, there is growing evidence that the interuterine environment has a strong influence on later postnatal health. This theory is based on the early statistical analysis of disease/longevity in babies with low birth weights in England by Barker, and has been called the "Barker Hypothesis". (More? Barker Hypothesis)
Each section of the notes covering early development and specific systems contain references to specific abnormalities (on Page 2 of each notes section). The best source for Australian statistical data is the Australian Institute of Health and Welfare National Perinatal Statistics Unit, UNSW which publishes "Congenital Malformations Australia" every 2 years. Be aware that some congenital abnormalities, by their nature, affect multiple systems. In the USA, the Center for Disease Control (CDC) keeps and publishes relevant statistical information. A very difficult issue in abnormal development are the many different Ethical implications.
This current page is a link to Normal and Abnormal Development and Population Data.
You should look at normal development. Development Notes
Alternatively, go on to look at Systematic Development of organs and tissues.
For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.
The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.