10. Floppy Baby & Dysmorphology Syndromes in Paediatrics.pdf

Floppy Baby & Dysmorphology Syndromes in Paediatrics Semester 5 Paediatrics MUCM Section 1 Floppy Baby Syndrome Learning Objectives 1. Describe the typical clinical features of a floppy baby 2. Differentiate between myopathy, lower motor neuron and upper motor neuron causes Floppy Infant Syn...

Floppy Baby & Dysmorphology Syndromes in Paediatrics Semester 5 Paediatrics MUCM Section 1 Floppy Baby Syndrome Learning Objectives 1. Describe the typical clinical features of a floppy baby 2. Differentiate between myopathy, lower motor neuron and upper motor neuron causes Floppy Infant Syndrome Previously described as Rag Doll syndrome (1968 Victor Dubowitz ) Presenting feature :  Hypotonia - main feature  Abnormal posture  Reduced or Diminished resistance to passive movement of joints leads to abnormal range  Motor developmental delay  Varies in severity and duration Frog-like position Scarf sign Approach to A Floppy Infant Establishing a diagnosis is important : Prognosis Management & Treatment strategies Genetic counselling. Characteristic posture manoeuvres to show hypotonia Slipping through the hands – Vertical suspension U Inverted U shape – Ventral suspension Excessive head lag - Pulling to sit from supine Examining The Hypotonic Infant 1. Alertness of Infant 2. 3. Any dysmorphic facies Level of hypotonia : With weakness = Without weakness = Lower Motor Neuron Or Muscle Lesions Eg : Anterior horn cell Peripheral nerve Neuromuscular junction Muscle. Upper Motor Neuron Lesions Floppy Weak Floppy Strong Eg : Cerebral cortex Chromosomal eg Down syndrome. Metabolic 4. Do Not Forget to examine Mother, too ! Facial weakness Ptosis Fatiguability Grip or Percussion myotonia What causes the “Floppiness”? Causes of A Floppy Infant Site Diseases Cerebral cortex Perinatal asphyxia Neonatal encephalopathy Kernicterus Cerebral palsy – atonic Down syndrome Inborn errors of metabolism – aminoacidurias Spinal cord lesions – anterior horn cell Spinal muscular atrophy Peripheral nervous Acute polyneuropathy Neuro-muscular junction Neonatal myasthenia gravis Infantile botulism Muscles Muscular dystrophies Congenital myopathies Congenital myotonic dystrophies Glycogen storage disease – Pompe’s disease Miscellaneous Protein energy malnutrition Prader – Willi syndrome The Motor Unit  The upper and lower motor neurons form a two-neuron circuit.  The upper motor neurons originate in the cerebral cortex and travel down to the brain stem or spinal cord  The lower motor neurons begin in the spinal cord and go on to innervate muscles and glands throughout the body.  Upper motor neuron weakness – caused by lesions within the cerebral cortex and corticospinal tracts down to, but not including, the anterior horn cell in the ventral spinal cord.  Lower motor neuron weakness – caused by lesions located in the anterior horn cell, peripheral nerve, neuromuscular junction, or muscle. Lower Motor Neurons begin from the anterior horn cell of spinal cord and innervate muscles and glands Upper Motor Neurons originate in the cerebral cortex and travel down to the brain stem or spinal cord Causes of “Strong” Floppy  Upper Motor Neuron Lesions (UMN)  Hypoxic –ischaemic encephalopathy  Cerebral malformations  Metabolic causes  Hypothyroidism  Chromosomal eg Down syndrome. Causes of “Weak” Floppy  Lower Motor Neuron Lesions (LMN)  Spinal Muscular Atrophy (SMA)  Congenital Hypomyelination Syndrome  Congenital Myasthenia gravis  Infantile botulism  Congenital Muscular Dystrophies  Congenital Myopathies Approach : History Taking Pre-natal history Reduced fetal movements or Polyhydramnios In utero infections Maternal exposures (drugs, alcohol intake). Neonatal history Preterm delivery, Delivery complications / Evidence of asphyxia and low A/S - suggestive of hypoxic – ischemic encephalopathy (HIE) Neonatal seizures, Past medical history Breathing or Feeding problems Symptoms of systemic illness Developmental history Delayed milestones Developmental regression Motor, social and speech-language incongruence. Family history Consanguinity Previous miscarriages and early childhood deaths Siblings with neuromuscular, metabolic or genetic conditions Physical CNS findings of a Floppy Infant Tone Power Reflexes Other CNS findings Central (UMNL) Increased (spasticity ) Normal Hyperreflexia Upgoing plantars Positive Babinski sign Lethargy Seizures Dysmorphic features Spasticity + clonus Disuse atrophy Peripheral(LMNL) Reduced Vs Reduced Hypo/absent Downgoing plantars or absent response Muscle Atrophy Fasciculations Investigations  Biochemistry – Serum electrolytes , serum calcium, glucose , serum creatine phosphokinase, serum lactate  Metabolic studies  Neuroimaging – CT scan / MRI brain  Electrophysiological studies - Electromyogram Nerve conduction test  Genetic – Chromosome karyotype, SMN gene, Prader Willi  Specialised - Muscle / nerve biopsy  Targeted investigations Spinal muscular atrophy  Degeneration of anterior horn cells in the spinal & brainstem  Commonest cause of LMN hypotonia  Incidence : 4-10 per 100,000  Autosomal recessive Types of Spinal muscular atrophy Onset during infancy SMA I Werdnig Hoffman syndrome - usually dies early SMA II presents after 6 months SMA III present after 10 months of age – achieve ambulation Spinal muscular atrophy  Profound hypotonia  Proximal weakness with some distal movement  Bright alert facies  Tongue fasciculations  Poor swallowing and feeding difficulties  Sparing of the diaphragm with abdominal breathing  Marked intercostal muscle weakness.  Absent deep tendon reflexes Molecular gene testing - homozygous deletions of exon 7 of SMN1 gene SMN1 gene is located at locus 5q11-q13. Other Causes of Floppy Infant Prader Willi Syndrome Congenital myopathy Congenital Myotonic Dystrophy Down Syndrome Evolving cerebral palsy Dysmorphology and Syndromes in Paediatrics Section II Learning Objectives 1. Recall the definition of dysmorphological terms 2. Record a good history 3. Recognize dysmorphic signs 4. Describe typical clinical features and diagnosis of Down syndrome 5. Know the risk factors for Down syndrome and prenatal diagnosis Dysmorphic Signs, Dysmorphology & Syndrome Dysmorphic signs - appearance that is unusual compared with the general population Dysmorphology – study of congenital malformation and recognition of patterns of malformation that occur in syndromes Terminology in dysmorphology -1 Terminology Examples Cause Malformation Dandy Walker Altered genetic or developmental processes Deformation Congenital talipes equinovarus (clubfoot) Mechanical forces in utero Dysplasia Skeletal dysplasia Abnormal development or growth of a group of tissues, organs, or cells Disruption Amniotic bands Physical forces interrupt or distort morphogenesis Terminology in dysmorphology - 2 Terminology Examples Cause Sequence Pierre Robbin Chronological order of abnormal development Syndrome Down Syndrome Cluster of malformations with a recognizable pattern VACTERL Co-occurrence of malformations without a known cause Association Causes Cause Percent incidence Genetic Chromosome Single gene 15 – 25 10 – 15 2 – 10 Multifactorial 20 – 25 Environmental Maternal diseases Uterine / Placental Drug / Chemicals 8 – 12 6–8 2–3 0.5 – 1 Twinning 0.5 – 1 Unknown 40 – 60 Clinical Approach Adequate History Taking –1  Antenatal history Fertility medications Techniques like IVF - invitro fertilization Fetal Movement (active, decreased) Exposures (medications, tobacco, alcohol, drugs, chemicals) Illnesses (fevers, exposures to infections eg rubella, cytomegalovirus ) Problems (bleeding, pre-term labor, abnormal prenatal testing or ultrasound) Adequate History Taking - 2  Birth history Presentation: breech/cephalic/oblique Delivery: vaginal, c-section (why?) Neonatal course (complications/problems and days hospitalized) Adequate History Taking -3  Neonatal history / status Anthropometric measurements – head circumference, weight, length  Newborn course Feeding problems Activity Obvious deformities Adequate History Taking - 4  Developmental history  Milestones achieved ?  Growth patterns Family history  Take a detailed, three-generation family history Pedigree Example of an Autosomal Dominant disorder Family history Ask for:  Birth defects  Other genetic diseases  Multiple miscarriages  Neonatal deaths  Parental ages and health status  Consanguinity and geographic origin Physical examination - 1  Growth monitoring Measurements of the child's weight, length, and head circumference Plot them on the standardized growth charts.  General appearance Body shape and size Physical examination - 2 Anthropometry Height, weight, head circumference, arm span US/LS ratio Head Shape, size, forehead anterior and posterior fontanelle Hair Colour, texture, hair whorl pattern, hair line, growth Eyes Slant, intercanthal distance, shape, size, cornea, sclera, iris (colour, coloboma), Fundus Ears Size, position, shape Mouth Size, shape, palate (narrow, high arched, cleft) Alveolar ridges Lips ( thick, thin, cleft, shape) Philtrum (small, long, simple, prominent) Chin & Malar region Micrognathia, retrognathia, hypoplasia of malar region Neck Short, long, webbed Physical examination - 3 Chest Hands & Upper Limbs Shape, inter nipple distance, sternum Shape, fingers, nails, clinodactyly Limb lengths, carrying angle Feet & Lower Limbs Shape, toes, big toe abnormalities, sandal gap Limb lengths, hip dislocation, edema Skin Colour, texture, hirsutism, sweating, pigmentary abnormalities Investigations  Cytogenetics is a mainstay of diagnosis in dysmorphology.  Molecular (DNA) diagnostics  Biochemical lab testing (to rule out any inborn error of metabolism, storage diseases etc.)  ECHO , X rays, ultrasound abdomen, MRI brain  Vision , hearing tests. Cytogenetics – karyotype analysis Cytogenetics -Fluorescence in situ hybridization (FISH) a microdeletion on chromosome 22 associated with DiGeorge syndrome Dysmorphic signs Cleft palate Cleft lip Ear defects Low set ears Microcephaly Pierre Robbin Syndrome Hands and Feet Deformities Polydactyly Syndactyly Amniotic Band Syndrome Skeletal Dysplasia GENETIC SYNDROMES Down Syndrome ( Trisomy 21) Commonest genetic disorder ( 1: 650 Live births ) Features : - Growth retardation - Varying degrees of intellectual disability - Craniofacial abnormalities - Upward slant eyes - Epicanthal folds - Flattened facies - Musculoskeletal : Single palmar crease, Clinodactyly, Brachydactyly, Sandal gap between 1st and 2nd Toe - Cardiac defects : VSD , AVSD, ASD - GIT : Duodenal atresia - Hypotonia Types of Down Syndrome Type Incidence Explanation Trisomy 21 Non-disjunction 95 % 3 separate copies of chromosome 21 instead of the usual 2 copies - Associated with advancing maternal age Translocation 3% an extra part or a whole extra chromosome 21 is present which is “trans-located” to a different chromosome Mosaic 2% mixture or combination Down Syndrome – karyotype analysis •. Risk of Down syndrome - advanced maternal age Ref : Br Obstet Gynaecol 1987 May;94(5):387-402. doi: 10.1111/j.1471-0528.1987.tb03115.x Maternal age (years) Risk All ages 1 in 650 20 1 in 1530 30 1 in 900 35 1 in 385 37 1 in 240 40 1 in 110 44 1 in 37 Antenatal test - for Down syndrome Screening Testing : ❑ Maternal serum screening( 15 – 18 weeks ) - Alpha-fetoprotein (AFP), unconjugated estriol and human chorionic gonadotropin (hCG) ❑ Ultrasound – done between 10 – 14 weeks - Nuchal Translucency Diagnostic Testing : ❑ Amniocentesis ( 12 – 15 weeks ) ❑ Chorionic villus sampling (10 – 12 weeks ) After antenatal diagnosis Current accurate information Counselling – geneticist, medical counselor Options – continue pregnancy termination of pregnancy Other syndromes Patau Syndrome ( Trisomy 13 )  Incidence : 1: 15,000  Small for age  Cleft lip and palate  Polydactyly  Clenched fists  Eye defects : micropthalmia anophthlmia  Cardiac defects  Omphalocele  Holo-prosencephaly  Most die by age 3 months Clinical features Weak cry Polyhydramnios Growth faltering Low-set, malformed auricles Clenched hand with overlapping fingers Rocker bottom feet Congenital heart defect Turner syndrome (45XO) Diagnosis may be missed until age of 5-6 yrs of age  Short stature  Webbed neck  Cubitus valgus  Renal anomalies  Cardiac defects - bicuspid aortic valve and coarctation of aorta) Noonan syndrome  Characteristic facies - downward slant eyes ( anti-mongoloid slant )  Short webbed neck with trident hair line  Pectus excavatum  Short stature  Cardiac defects – Pulmonary stenosis , Atrial septal defect Mild learning difficulties Summary  Recognise A Floppy Infant & the Causes – UMN Vs LMN  Spinal Muscular Atrophy disease – commonest cause of LMN Floppy  Recognise dysmorphic features in a Baby or Child  Down syndrome – commonest chromosomal disorder  Management of problems / complications  Palliative care may be the best option in certain complex syndromes  Genetic analysis  Genetic counselling : Risks for future pregnancies Prenatal Testing Thank you