Micrognathia - the mandible is small

Retrognathia - mandible size is essentially normal but is retrognathic (posterior-placed) because the cranial base angle is larger than normal

Cleft palate - defect in palate (primary or secondary)

Glossoptosis - tongue is not actually larger than normal, but because of the micro/retrognathia, is large for the airway and therefore causes varying degrees of obstruction

Interestingly, when Dr. Pierre Robin first described the sequence, his triad consisted of: micrognathia, glossoptosis, and respiratory distress. Only later was cleft palate added to the list of anomalies.

Many now state that the three essential elements of Robin sequence are:
(1) micrognathia or retrognathia, (2) Cleft palate, and (3) Glossoptosis, often accompanied by airway obstruction.

The case definition of Robin sequence thus still varies. That being said, all definitions seem to acknowledge the fact that virtually all patients have mandibular deficiency of some form, whereas cleft palate and/or airway obstruction are highly variable in severity and may be absent in some cases.

Robin sequence is a series of anomalies all initiated by one developmental problem, which is considered to be the mandibular deficiency. Restricted growth/posterior positioning is thought to result in impaction of the tongue between the palatal shelves, preventing their elevation and eventual fusion. It also results in glossoptosis relative to small/retrognathic mandible, with airway obstruction caused by the tendency of the tongue to retract with velum against posterior pharyngeal wall, especially when supine and with neck flexion.

The mandibular deficiency results from deformation, malformation, or connective tissue dysplasia.

Isolated cases of Robin Sequence (40-75% of all causes) are thought to be primarily deformational - from intrauterine forces acting on the mandible, which restrict its growth. Some deformational cases of Robin sequence have been associated with oligohydramnios, but this is not a prerequisite. In most such cases, mandibular catch-up growth is expected after birth once intrauterine forces are removed (unless severe).

Cases of malformation are considered mostly syndromic, such as that seen in 22q11.2 microdeletion (15% of all syndromic causes) and Treacher-collins syndrome. Connective tissue dysplasia is also often syndromic, and Stickler syndrome is an example - comprising 25% of all syndromic cases of Robin sequence. Syndromic cases are often referred to as "Robin complex", due to the fact that the Robin sequence is often only a part of a complex of anomalies caused by a chromosomal aberration.

Up to 1/3 of all cases of Robin sequence do not have an identified specific syndrome but are associated with multiple other anomalies.

Other than the obvious facial anomalies and associated airway obstruction, one of the other ways such infants may present is with feeding difficulties - but not considered essential feature.

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Gary, this question is correct, but probably not at the level of a student. This would not be considered core knowledge; definitely core for a resident.

Ketamine is the only listed medication that is not associated with hypotension, and may in fact can increase BP. Therefore, it is usually used in combination with a neuromuscular blocking agent +/- atropine or other sedating medications prior to RSI in hemodynamically unstable patients.

Ketamine can be given IV @ 1-2 mg/kg. It is a dissociative anesthetic with analgesic properties. It also inhibits catecholamine reuptake in the neuromuscular junction. It is lipophilic, has a rapid onset, lasts for 15-60 mins. Its benefits are that it has limited respiratory depression, may increase BP/HR/cardiac output, and has some bronchodilatory properties (making it a preferred drug in patients with asthma), in addition to the fact that it often provides some amnesia of the events. Side effects include HTN, increased laryngospasm and airway secretions, and emergence reactions (hallucinations during recovery from dissociative state). In severely ill patients who are catecholamine-deplete, inhibition of catecholamine reuptake may lead to myocardial depression.

Propofol can be given IV 2-3 mg/kg. It is a non-barbituate useful as an anesthetic induction agent, or as a short-acting sedative, but is a pure sedative/amnestic with NO analgesic effect. Its benefits are that it has a rapid onset of action (<1 min) and because is highly lipid soluble, has a short duration of action (3-10 mins), with no active metabolites. Its biggest side effects are respiratory and cardiovascular depression, leading to decreased blood pressure and heart rate, especially in those who are hypovolemic. Propofol is contraindicated in patients with allergies to soybean or eggs.

Fentanyl can be given at 2-4 mcg/kg IV. As it is an opioid, it provides analgesia, anxiolysis, and mild sedation. It does not induce amnesia of any significance. It is typically coadministered with benzodiazepines for added sedation, anxiolysis, and amnesia. Fentanyl is a very potent opioid that rapidly crosses the blood-brain barrier and thus has a rapid onset of analgesia (<90 s). Rapid tissue redistribution limits duration of action to about 30-60 minutes.
Like all other opioids, its side effects are hypotension and respiratory depression, which are potentiated when used in combination with benzodiazepines. However, it does cause less histamine release and CV depression in comparison with other opioids, so would have been the next best answer in this case of hemodynamic compromise.

Last, midazolam can be used IV @ 0.1-0.2 mg/kg. It is a (BDZ) benzodiazepine with unique lipophilic (at pH>4) and hydrophilic properties. Its lipophilic properties allow it to easily cross blood-brain barrier, with onset in < 5 minutes (fastest of its class), duration 30-60 mins. As it is a BDZ it potentiates GABA, produces sedation, amnesia, anxiolysis but has NO analgesic properties. Its most significant adverse effect is respiratory and cardiovascular depression, resulting in hypotension and hypoxemia. It also potentiates such effects of nacrotics. Also, children may have a paradoxical disinhibition and increased agitation at low doses.

This is a common question that parents ask about, and the answer provided below is based on the CPS guidelines for nutrition in a term infant. Obviously, breast milk is still recommended as sole nutrition for first 6 months of life wherever possible.

It is estimated that 20% of infants on infant formulas take soy protein-based formulas, and presumably most are chosen because of a perceived or true allergy to cow's milk protein. However, routine indications for appropriate use are limited to just 2 settings - infants with galactosemia, or those being fed vegan diets (a diet which in actuality, is not recommeded until 2 years of age)

As mentioned, most infants taking soy-protein based formulas are on it because there is a perception that they are indicated for the dietary management of infants with proven cow's milk allergy, or in the prevention of atopy. However, both of these points are controversial:

With respect to the treatment of cow's milk protein allergy, there has been significant cross-reactivity noted between cow's milk protein-based and soy protein formulas. Thus, if an infant is suspected of having cow's milk protein induced gastrointestinal disease and is on a formula, the recommended switch would be to an extensively hydrolyzed (casein-based) formula such as Alimentum or Nutramigen as it is significantly less allergenic. Based on initial response, a potentially more allergenic soy-protein based formula (if symptoms resolve) or less allergeic amino-acid based formula (if symptoms persist) may be trialled therafter.

Similarly, if a baby is at high risk (based on FHx) for cow’s milk protein allergy, the recommended choice of formula would NOT be soy-protein based formula. Again, it would be the less hypoallergenic protein hydrosylate formulas. If there is no documented allergy, oprions include the less extensively hydrolysed whey-based formulas (e.g. Goodstart), or the extensively hydrolysed casein- hydrosylates (Progestamil, Nutramigen). Whey- hydrosylate formulas are a bit more allergenic, but have a better taste and are often better tolerated so are recommened in this setting.

As you might have presumed by now, there is a lack of evidence demonstrating a reduced prevalence of atopic diseases in high-risk infants fed soy protein-based formulas in the first 6 months of life.

Going through the final alternative answer, in fact all soy formulas sold in Canada are iron-fortified, and so additional iron supplementation would not be necessary.

I should also add, soy-based formulas are also lactose-free, so the AAP lists a 3rd indication for their use, which wold be for congenital or acquired lactase deficiency. However, there are also cow's milk protein based formulas that are lactose-free and may be used as well in this setting.

90% of newborns have first passage of stool, known as meconium, within the first 24 hours of life. Meconium is a thick, dark, greenish-black substance composed of intestinal cells, lanugo, mucus and bile.

If meconium is not passed within this time frame, consider an intestinal obstruction, anatomic abnormalities, Hirschsprung’s disease or Cystic Fibrosis.

Note that premature infants commonly have delays in passage of first stool (after 24 hours).

Microbiology of Periorbital and Orbital Cellulitis: Staphylococcus aureus/epidermidis, and S pyogenes (GAS) account for 75% of pediatric periorbital infections at present. Similarly, Staphylococcus and Streptococcus are the two most common organisms responsible for orbital cellulitis. Community-acquired MRSA has become increasingly prevalent, and must be considered in cases where clinical improvement does not occur on empiric antibiotic therapy. Haemophilus influenza type b was historically associated most commonly with orbital cellulitis and hematogenously spread periorbital cellulitis, but has been on the decline since the introduction of the Hib conjugate vaccine. S. Pneumo infections are similarly on the decline. Polymicrobial infections also can occur in odontogenic disease.

Investigations: Routine blood cultures should not be done for patients unless there is evidence of bacteremia or systemic illness. One should attempt to obtain swabs for culture and sensitivity of pathogens involved. CRP, ESR, WBC being high may suggest orbital cellulitis over periorbital, but should never be used in isolation to make a diagnosis. A FSWU should be done if the patient appears toxic or there is evidence of neurologic involvement.

CT scanning is ideal for identifying extent of orbital inflammation. Indications for CT scanning include: (1) eyelid edema that makes complete examination impossible, (2) CNS involvement, (3) deteriorating visual acuity/color vision, gross proptosis or ophthalmoplegia, (4) clinical deterioration or no improvement after 48 hours of adequate treatment

Reasons for inpatient management: (1) evidence of orbital cellulitis, (2) can’t fully examine eye, (3) systemically ill or evidence of CNS involvement, (4) need for parenteral antibiotics

Oral versus Parenteral Antibiotics: All patients with orbital cellulitis should be admitted for IV antibiotics, until significant improvement can be achieved. With respect to periorbital cellulitis, there is no evidence that IV antibiotics are better than oral antibiotics for the management of simple periorbital cellulitis, so oral is preferable in these cases. In cases of periorbital cellulitis as a consequence of hematogenous seeding, patients should be admitted and given parenteral antibiotics.

With these pearls in mind, let’s examine the 5 scenarios:

Patient 1: This is a description of a simple case of periorbital cellulitis following infected insect bite. For such cases associated with superficial breaks in skin (impetigo, eczema, bite, abrasion), most common pathogens are Staph aureus and Strep pyogenes. Empiric management with oral coverage for these organisms should be started, usually in the form of cloxacillin or a first-generation cephalosporin. If MRSA is suspected, clindamycin or TMP-SMX should be started. Follow-up should be arranged, as clinical improvement should be evident within 48 hours. Duration of therapy is usually 7-10 days.

Patient 2: This is a description of a case of periorbital cellulitis, in this case secondary to extension of infection from an external stye (hordeolum), which is an infection of the sebaceous/sweat glands at the base of the eyelashes and can be seen as small red bumps localized on the eyelid. The most common pathogen is Staph aureus. However, as the cellulitis has not improved after 48 hours of cephalexin, complications or resistant organisms must be considered, particularly CA-MRSA. As there is no evidence to suggest any complications, it would still be reasonable at this point to continue oral antibiotics, this time with MRSA coverage, with follow-up in 24-48 hours for improvement. Warm compresses may also be useful in hastening drainage.

Patient 3: This is a case of orbital cellulitis as there is evidence of increased intra-orbital pressure. The likely source in this case is rhinosinusitis, in which case the most likely pathogens are S pneumoniae, H influenzae, and Moraxella catarrhalis. In this setting, the patient should be CT scanned to determine the extent of orbital involvement and rule out complications such as intracranial infection or cavernous sinus thrombosis. A FSWU should be considered. Inpatient management, ophthalmology assessment, and initial parenteral antibiotic therapy is all warranted. IV antibiotics should have empiric coverage for both organisms associated with rhinosinusitis, as well as anti-staphylococcal and anti-streptococcal coverage with strong consideration of MRSA coverage. A reasonable regimen here would be IV 2nd/3rd generation cephalosporin +/- clindaymycin or vancomycin. Once significant improvement has been made, a switch to oral antibiotics can be made, with total 10-14 days of coverage.

Patient 4: This is a case of dental abscess with spread and periorbital cellulitis as a result. Pathogenic organisms in this case may be varied, including mixed aerobic and anaerobic bacteria. Management in this setting is two-fold – evaluation by a dentist with abscess drainage and possible tooth extraction, and antibiotic coverage (oral or more likely parenteral) with clindamycin or amoxicillin-clavulanate.

Patient 5: In any patient, particularly those younger than 3, that presents with rapidly progressive eyelid swelling and systemic signs of illness preceded by a viral URTI, hematogenous spread with periorbital seeding should be strongly considered. Pathogens include H influenzae, S pneumoniae, S pyogenes and S aureus. This requires inpatient management with IV antibiotic coverage of both gram +ve and gram –ve organisms. Thus, management would be similar to that of case 3, with a reasonable regimen of IV 2nd/3rd generation cephalosporin +/- clindamycin or vancomycin if MRSA suspected. Once significant improvement has been made, a switch to oral antibiotics can be made, with total 10-14 days of coverage. A FSWU should be strongly considered in this case. CT may also be considered.

The patient history and clinical manifestations are characteristic of Juvenile Myoclonic Epilepsy. Patients with Juvenile Myoclonic Epilepsy initially experience myoclonic jerks upon waking in the morning, with symptoms subsiding later in the day. Typically a few years later, the patient develops generalized tonic-clonic seizures, which can be precipitated by sleep deprivation or other stressors. Onset is usually between ages twelve and sixteen years.

Lafora disease is a type of severe, progressive myoclonic epilepsy that usually appears in children between ages ten and eighteen years. Initial symtoms include myoclonic jerks that increase in intensity and frequency with disease progression. Neurological findings become prominent, particularly mental deterioration within the first year of onset.

Patients with Frontal lobe epilepsy experience seizures originating in the frontal lobe and have manifestations (including motor and behavioral) concurrent to the specific area affected.

Absence seizures often occur in school-age children, and may be mistaken for inattention or daydreaming.

Acute leukemia occurs 14 times more frequently in children with T21 than in the general population, which works out to a risk of leukemia of 1-1.5%.

In the general population, approximately 80% of all leukemias in children are ALL, whereas 11-17% are AML. This ratio of ALL to AML is actually similar in patients with T21 to that of the general population.

However, T21 patients with AML often develop a specific subtype of AML known as acute megakaryoblastic leukemia (aka AML-M7 or AMKL). The incidence of AMKL is approximately 500 times greater in children with T21 than in the general population. AMKL often develops by 4 years of life, and when it presents in the first 2 years of life, it is invariably associated with mutations in GATA-1. GATA-1 is a gene on the X chromosome that encodes a transcription factor that controls megakaryopoiesis, and has been identified in blasts of patients with trisomy 21 and AMKL. This information suggests that AMKL may result from a gene mutation, which may be acquired in utero and serve as a biomarker for an increased risk of transient leukemia and subsequent AMKL.

Interestingly, in earlier onset AML, patients with T21 have much better outcomes (>80% long-term survival rates) and often require less intensive therapy than children without T21 (<70%). In contrast, myeloid leukemias in people with T21 > 4 years are usually negative for GATA-1 mutations, and their prognosis does not differ from AML in patients without T21.

In patients with T21, ~10-20% of newborns develop a transient leukemia or myeloproliferative syndrome. It is often characterized by blasts in the peripheral blood, with hemoglobin, platelet, and neutrophil counts typically being normal. It resolves spontaneoously in days to weeks and does not require treatment. However, it is important and must be screened for in all infants with T21, because 20-30% of patients with transient leukemia later develop AMKL. GATA-1 mutations are often identified in such patients.

The risk of developing acute lymphoblastic leukemia (ALL) is approximately 10 to 20 times higher in T21 children than in the general population. The clinical presentation and epidemiology of ALL, as well as the expected outcome of treatment is the same in patients with T21 than in other children.

Molluscum Contagiosum is the most likely diagnosis given the history (playmate having similar condition) and physical presentation, particularly the central umbilication and core of the papules.

Molluscum Contagiosum is a viral disease caused by a DNA poxvirus and transmitted via direct skin to skin contact or sharing objects touching the skin. Patients present with flesh-colored papules that contain viral bodies, usually appearing on the extremities, trunk and face. Highest incidence is in children less than 5 years of age. Usually, Molluscum Contagiosum is diagnosed by simple identification of the characteristic central umbilication and core of the papules. Treatment options include topical vesicants and cryotherapy among others. Or, simply waiting for disappearance is advised, as most cases resolve within weeks to months.

Atopic dermatitis, or eczema, is the most common inflammatory skin condition in childhood. It typically presents in skin creases or flexure surfaces as a red, pruritic dermatitis in variable stages of vesicles, scaling and excoriations.

Warts, caused by Human Papilloma Virus, are present in 10-20% of school-aged children. There are many different types, most appearing on the hands and feet.

Granuloma annulare, a benign inflammatory dermatosis, usually presents with groups of papules in an annular arrangement.

The DSM-IV-TR defines mental retardation as follows:
A. Significantly subaverage intellectual functioning (IQ of approximately 70 or below)
B. Concurrent deficits or impairments in adaptive functioning in at least 2 of the following areas: communication, self-care, home living, social/interpersonal skills, use of community resources, self-direction, functional academic skills, work, leisure, health, and safety
C. Onset before age 18 years

Hyperactivity, impulsivity and inattention are clinical signs of Attention Deficit Hyperactivity Disorder (ADHD). Although many children with mental retardation present with these behaviors, this may reflect their typical developmental level or a concurrent diagnosis of ADHD. As such, these findings are not included in the DSM-IV diagnostic criteria for mental retardation.

A bit about transitioning from fetal to neonatal circulation and its effect on PVR:
1) Pulmonary vascular resistance (PVR) is as high as the systemic
vascular resistance in a fetus near or at term because:
a Large amounts of smooth muscle in pulmonary arteriole walls
b Lungs full of fluid -> alveolar hypoxia -> pulmonary
vasoconstriction
2) RV is larger and more dominant than the LV as it handles a larger percentage of the combined ventricular output than the LV.
3) At birth:
a Lung expansion leads to increased alveolar oxygen tension, and
with it, a rapid fall in PVR (oxygen has a vasodilating effect
on the pulmonary vasculature), increased pulmonary blood flow,
and decreased pulmonary artery pressure
b Meanwhile, removal of the low resistance placental circulation
leads to an increase in systemic vascular resistance (SVR), and
cessation of umbilical vein flow leading to closure of ductus
venosus
c Increased Left atrial pressure occurs because of increased
pulmonary blood flow and subsequent pulmonary venous return to
the LA, while decreased right atrial pressure results from
closure of the ductus venosus. This relative pressure
difference results in functional closure of the foramen ovale
4) Functional closure of the ductus arteriosus occurs within 10 to
15 hours after birth by constriction of its medial smooth
muscle, which contracts secondary to increased postnatal oxygen
concentration in the systemic circulation
5) Although the PVR falls after birth because of pulmonary
vasodilation, it continues to fall in the first 6-8 weeks of
life, likely because of thinning of the medial layer of the
pulmonary arterioles. It is further reduced over the next 2
years, presumed because of increases in numbers of alveoli and
their associated vessels

This last point helps explain why the LEAST likely etiology of this murmur is a large VSD.
1) Although the PVR drops immediately after birth, it is still relatively higher than that in an infant/child for reasons aforementioned. Since shunting is determined by the relative difference in PVR and SVR, the pulmonary vascular resistance often takes weeks to sufficiently decrease to allow significant left to right shunting through cardiac lesions.
2) Because PVR falls more quickly with small VSDs compared to large VSDs, shunting (and therefore an audible murmur) occurs earlier with small VSDs.

(Why? in large VSD, the relatively high LV pressure can be transmitted directly to the pulmonary artery through the defect, thus maintaining a high pulmonary artery pressure and further delaying the fall in PVR - this high pressure is not as well transmitted through a small VSD, and so PVR falls more quickly in small VSDs)

For all of these reasons, the holosystolic murmur associated with a large VSD does NOT usually appear in the 1st 2 weeks, and often longer. In contrast, a smaller VSD may be auscultated earlier (early systolic).

It is also noteworthy that signs of CHF (tachycardia, tachypnea, hepatomegaly, cardiomegaly) do NOT present until PVR falls enough to allow for significant shunting, so newborns with large VSD’s are often asymptomatic over a similar time period.

This case is also designed to illustrate that newborns have some unique cardiovascular findings that are normal for their age. The history and physical examination described above is considered normal for a newborn, despite some features that would be considered concerning in older children and adults:

1) Vitals:
a) HR normally ranges from 70 to 180, while RR can be 30-60.
b) Mild desaturations in an otherwise well neonate are not unusual, and are attributed to intrapulmonary R to L shunts through portions of the lungs that are not fully expanded and/or small R to L shunts through patent foramen ovale
2)The PMI is often found at the LLSB rather than the apex, and the S2 may be single in the first days of life.
Why? Right ventricle is still relatively hyperactive, and still generates the PMI (point of maximal impulse). The S2 may be single because the PVR is still relatively high and so a degree of relative pulmonary hypertension causes earlier closure of pulmonary valve, bringing A2 and P2 closer so that they may be heard as a single sound
3) Acrocyanosis (intermittent, bilateral, symmetric bluish discoloration of the hands and feet) is common in the neonatal period, attributable to vasomotor instability as the newborn adjusts to extrauterine life.
4) Liver edge is normally palpable 1-2 cm below the right costal margin, whereas hepatomegaly may suggest a heart defect
5) THREE INNOCENT MURMURS are commonly heard in the newborn period. All are systolic, and can be accounted for by the etiologies mentioned as the other possible answers.

Innocent murmurs in newborn (SEM = systolic ejection murmur; mid-systolic and cresc-decrescendo pattern):
1. Persistent pulmonary flow murmur of newborn
a) Etiology: In fetus, the main Pulmonary artery trunk is large, but branch pulmonary arteries are hypoplastic (because of low pulmonary blood flow in fetal life). After ductus closes, turbulent flow from large pulmonary artery (PA) into (physiologic) smaller branches at right angles creates murmur.
b) Description: ULSB, SEM, I-II/VI (may be louder in small, preterm babies), Wide radiation (along smaller branches of PA)
c) Comments: If persists beyond 6 months, consider PA stenosis and refer

2. Transient systolic murmur of Ductus Arteriosus
a) Etiology: closing ductus arteriosus in 1st day of life
Note: it is often heard as a systolic rather than a continuous murmur in the newborn because during diastole, systemic & pulmonary pressures are similar so there is little to no L to R shunting through the PDA during this phase. The murmur is noted during systole when L>R pressures and shunting occurs.
b) Description: ULSB, mid-systolic crescendo (SEM-like), I-III/VI
c) Comments: Murmur may persist in PDA (premature, respiratory
distress, other CHD)

3. Transient systolic murmur of TR
a) Theory: Minimal tricuspid valve abnormality, in addition to the relatively high pulmonary vascular resistance, results in tricuspid regurgitation. This murmur disappears as PVR falls (as opposed to VSD murmurs, which increase as PVR falls)
b) Description: II+/VI, similar to VSD in that is holosystolic, albeit tends to be lower pitched and may be loudest at RLSB or LLSB.
c) Comments: usually audible in setting of sick newborn with lung disease and PPHN, not as commonly heard in a well-appearing baby.