Developmental milestones Flashcards
What is tested for in the neonatal heel prick screening test?
Galactosaemia Immunoreactive trypsinogen (Cystic fibrosis) Inborn errors of metabolism Phenylketonuria (PKU) TSH (congenital hypothyroidism) Sickle cell disease
Causes of developmental disability
Drug and toxic substance poisoning (e.g. Foetal alcohol syndrome) Genetic disorders (Down syndrome, Fragile X, Prader willi, velocardiofacial syndrome) High risk pregnancies (extremes of age, drug therapy, maternal DM, birth asphyxia, premature, congenital TORCH) Environmental factors (e.g. lead poisoning) Metabolic (PKU, hypothyroidism, halactosaemia, Tay Sachs) Childhood accidents Malnutrition Neonatal Jaundice Postnatal infections (meningitis) Recognised syndromes (Autism, Landua Kleffner) Idiopathic
Red flags in gross motor development
Reduced movement on one side Poor head control after 4 months Persisted of primitive reflexes after 6 months Not sitting after 7 months Increased or decreased tone at any age
Red flags in fine motor development
Early handedness before 18 months Not reaching after 5 months Not transferring after 9 months Not feeding self after 18 months Not drawing person by 3 years
Red flags in language/speech development
Stutter Hearing difficulty No words after 18 months No combination after 2 years Poor articulation after 3 years No 3-4 word phrases after 4 years Echolalia after 3 years
Red flags in social development
Obsessions at any age Poor eye contact at any age Lack of responsiveness after 3 months Not waving bye by 14 months Persistent mouthing after 15 months Not pointing after 15 months
Prevalence of down syndrome (in general and per ages)
1 per 600 live births 30: 1/1000 35: 1/400 40: 1/100 45: 1/30
First trimester screen for trisomy 21
performed at 11-13 weeks GA Ultrasound - increased nuchal translucency Largely increased free bhCG Reduced Preganncy-associated plasma protein-A (PAPP-A)
Second trimester (quadruple) screening test for trisomy 21
15-18 weeks GA Reduced maternal serum AFP Reduced unconjugated estriol (uE3) Largely increased total hCG Largely increased inhibin A
Diagnostic antenatal testing for down syndrome
Chorionic villus sampling: - performed at 12-14 weeks - 1% risk of pregancy loss Amniocentesis - performed at 15-18 weeks - 0.5% risk of pregnancy loss
Clinical features of Down syndrome present at birth (10)
Hypotonia Poor moro reflex up-slanting palpebral fissures Small low-set ears Flat facial profile Simian crease (single palmar crease) Dysplasia of mid phalanx of fifth finger (incurving of little finger) Hyperflexibility of joints Excess skin at nape of neck Dysplasia of pelvis
Epidemiology of Fragile X syndrome
1/1000 prevalence Commonest form of X-linked intellectual impairment Twice as common in males Carrier rate 1/250 in women Associated with autism spectrum disorders and epilepsy
Clinical features of Fragile X syndrome
Macrocephaly Large ears Prominent forehead and chin (long face) Hyper-extendable joints and flat feet Testicular enlargement (>25mL after puberty) Intellectual and learning disability Developmental delay Behavioural problems (hyperactivity, inattention, gaze aversion, stereotypic movements, hyperarousal, unusual speech patterns) Often a family history of similar issues
Diagnosis of Fragile X syndrome
DNA analysis to identify the Fragile X mental retardation gene (FMR1)
What is Turner’s syndrome?
A chromosomal disorder involving complete or partial absence of the second X chromosome in phyenotypic females, typically presenting with short stature and premature ovarian failure
Phenotypical features of Turner’s syndrome
Short stature Webbed neck Shield chest Widely spaced nipples Underdeveloped breasts Cubitus valgus (bowing of arm) Congenital lymphoedema of hands and feet High-arched palate Short 4th and 5th metacarpals Down-sloping eyes, ptosis
Other (non-phenotypical) features of Turner’s syndrome
Ovarian failure: primary amenorrhoea, no pubertal development (in most) - some may develop then have secondary amenorrhoea Short stature Renal anomalies in 40% - collecting system malformations - Horseshoe kidneys - malrotation and positional abnormalities Cardiovascular disease (bicuspid AV or coarctation)
Diagnosis of Turner syndrome
Peripheral white cell karyotype (+/- FISH if inconclusive) + then screen skeletal system, renal system, heart and pelvic ultrasound
Diagnostic criteria for Turner’s Syndrome
Complete or partial X monosomy Short stature (below 2nd percentile) Premature ovarian failure OR heart defects
What is Marfan syndrome
An inherited disorder of connective tissue, causing loss of elastic tissue and affecting numerous body systems including skeletal and cardiac
What is the inheritance pattern of Marfan syndrome?
Autosomal dominant 25% are sporadic mutations
Incidence of Marfan syndrome
1/10,000
What is the mutation in Marfan syndrome
A mutation in the fibrillin-1 gene (chromosome 15)
9 MSK, 2 CVS, 3 Occular
Phenotype of marfan syndrome
Highly variable
Musculoskeletal System:
- Tall stature
- Long limbs
- Long fingers (arachnodactyly)
- Joint laxity and flat feet
- Chest deformity (Pectus excavatum), kyphoscoliosis
- Long narrow face
- Deep set eyes
- High narrow palate
- Dental crowding
Cardiovascular
- Mitral valve prolapse
- Dilation of the ascending aorta (50%)
Eye
- Ectopia lentis (dislocation of the lens)
- Severe myopia
- Retinal detachment
Complications of Marfan syndrome
- Aortic dissection and rupture (due to dilation of the ascending aorta)
- Spontaneous pneumothorax
- Striae
- Hernia
- Lower life expectancy (72 avg)
What is neurofibromatosis?
A genetic disease which disturbs cell growth in the nervous system, leading to the development of multiple soft tumours (neurofibromas) and other complications.
What are the different forms of neurofibromatosis
Neurofibromatosis 1
Neurofibromatosis 2
Schwannomatosis
Each are clinically and geneticall distinct from eachother
Prevalence of neurofibromatosis
1/3000
NF1 is most common
Inheritance pattern of neurofibromatosis
50% is inherited in autosomal dominant pattern
50% is sporadic mutation
Defect in neurofibromatosis
Neurofibromin gene - expressed in kidneys, brain, spleen and thymus
Clinical manifestations of neurofibromatosis
Cafe-au-lait macules: >6
Freckling in axillary and inguinal areas
Neurofibromas
Optic pathway gliomas (reduced visual acuity, colour fision, pupillary function + proptosis and optic nerve atrophy)
Lisch nodules
Bone abnormalities
Neurologic abnormalities
(cognitive, learning, seizures, macrocephaly, peripheral neuropathy)
Hypertension
What is a Lisch nodule?
Raise, tan-coloured hamartoma of the iris that does not affect vision and is best seen through a slit lamp examination though may be visible with a direct ophthalmoscope
What is a neurofibroma
A benign peripheral nerve sheath tumour comprised of a mixture of Schwann cells, perineural cells and mast cells
- Cutaneous
- most common tipe
- soft, fleshy, sessile or pedunculated tumours
- non-tender and mobile
- Plexiform
- may be located superficially and assocaited with overgrowth of skin and soft tissue
OR - may be located deep inside the body - appears as thickened nerve
- may be located superficially and assocaited with overgrowth of skin and soft tissue
Complications of neurofibromatosis
Hypertension
Scoliosis
Bone problems
Plexiform neurofibromas (usually present at birth)
Spine and brain tumours (usually benign)
Speech delay
Epilepsy
What is Klinefelter syndrome?
A chromosomal disorder of males in which there is an additional X chromosome, hence the karyotype 47 XXY
Epidemiology of Klinefelter syndrome
- Birth incidence 1/700 live born males
- Most common chromosomal disorder in men
- Most common cause of mal hypogonadism
- Many men are never diagnosed, those who are are diagnosed as adolescents with delayed puberty or as adults with infertility
- Increased prevalence of cryptorchidism
Phenotypic features of Klinefelter syndrome (18)
- Tall stature
- Long limbs
- Small testes
- Undescended testes
- Gynaecomastia
- Female fat distribution as ages
- Infertility
- Behaviour problems
- Less facial and body hair/decreased shaving frequency
- Low libido
- Poor erections
- Fatigue
- Osteoporosis
- Depression
- IQ lower than siblings
- Difficulties with language and motor development
- Lower attention span
- Poor muscle tone
Management of Klinefelter syndrome
- Testosterone
- treatement at puberty will lead to more normal male development
- Early access to reproductive medicine i.e. in teenage years to store sperm to enhance reproductive chance
Complications of Klinefelter’s syndrome
- Pulmonary diseases
- Chronic bronchitis
- bronchiectasis
- Emphysema
- Cancers
- Germ cell tumours
- Breast cancer
- Non-Hodgkin lymphoma
- Varicose veins - leg ulcer
- SLE
- Diabetes Mellitus
Oedema of hands and feet in a newborn indicates what
A very rare clinical sign, high likelihood of Turner’s syndrome, thus warrants prompt investigation and karyotyping
