3.1 Movements Resembling Neonatal Seizures

In the newborn infant, there are several nonepileptic motor phenomena. They may be difficult to differentiate from seizures. Tremor, jitteriness, and myoclonus may be benign signs in an otherwise healthy infant, but may also signal a pathological condition. Examples include metabolic disturbance, infection, stroke, drug withdrawal, etc. These conditions show similarities to reflex behaviors of the neonate; however, they are not associated with ictal electroencephalogram (EEG) changes. They are often seen in hypoxic-ischemic encephalopathy. These types of seizures are considered exaggerated reflex behaviors due to release of brainstem facilitatory centers (for generating reflex behaviors) without cortical inhibition. They are also called brainstem release phenomena.

1. 
   

   Benign nocturnal myoclonus/Benign neonatal sleep myoclonus: Sudden jerking movements of the limbs during sleep occur in normal people and requires no treatment. May occur focally during nonrapid eye movement (non-REM) sleep. Video EEG monitoring shows no electrographic seizures.

   
   
2. 
   

   Jitteriness or tremulousness: Low-frequency, high-amplitude shaking of the limbs and jaw in response to stimulation. Occurs in newborns with perinatal asphyxia some of whom have seizures and require an EEG monitoring for differential diagnosis. Jitteriness is not associated with ocular deviation. It is stimulus sensitive (e.g., easily stopped with passive movement of the limb). The movement resembles a tremor, and no autonomic changes are associated with it. Seizures often are associated with ocular deviation and are not stimulus sensitive. Autonomic changes frequently accompany them. The movements are clonic, unlike the tremor like movements or jitteriness.

   
   
3. 
   

   Nonconvulsive apnea: Irregular respiratory patterns of 3–6 seconds, followed by 10–15 seconds of hyperpnea without significant changes in heart rate, blood pressure, temperature, or skin color. It affects premature infants and is caused by immaturity of the respiratory centers in brain stem and not by a pathologic condition.

   
   
4. 
   

   Opisthotonos: A prolonged arching of the back probably caused by meningeal irritation. It is observed in the infantile Gaucher’s disease and kernicterus, and must be differentiated from tonic seizures and decerebrate posturing.

   
   
5. 
   

   Benign myoclonus: Spasms in clusters increasing in frequency and intensity over weeks, then usually stop after 3 months with the exception of a few episodes, but no spasms occur after 2 years of age. The infants are neurologically normal, their EEG and CT scan of head are normal.

   
   
6. 
   

   Neonatal hyperekplexia or motor automatisms (startle disease): Clinically hyperekplexia is characterized by pathological and excessive startle responses to unexpected auditory and tactile stimuli (sudden noise, movement, or touch) and severe generalized stiffness (hypertonia in flexion which disappears in sleep). It is usually a familial condition which is inconsistently associated with EEG seizures and are considered as nonepileptic.

Reuber M, Elger CE. Psychogenic nonepileptic seizures: review and update. Epilepsy Behav 2003;4(3):205–216

3.2 Pallid Breath-Holding Spells

These episodes are precipitated by a sudden, unexpected unpleasant stimulus such as a mild head injury (without associated crying) followed by collapse with pallor, diaphoresis, bradycardia and loss of consciousness. The patient may be limp, and have posturing and clonic movements, and may progress into a generalized tonic–clonic seizure presumably due to cerebral ischemia.

Breath-holding spells are often mistaken for epileptic seizures and it is important to differentiate the two to avoid unnecessary treatment with anticonvulsants.

Swaiman KF, Ashwal S, Ferrieto DM, eds. Pediatric Neurology: Principles and Practice. Nonepileptiform paroxysmal disorders and disorders of sleep. 4th ed. St Louis: Mosby Elsevier; 2006

3.3 Pseudoseizures

Pseudoseizures are episodic, behavioral spells that mimic true epileptic seizures. They are common, accounting for 5–20% of the outpatient epilepsy population. Of patients with pseudoseizures, 10–40% also have epileptic seizures. Majority of patients are female between 15–35 years of age, however these are also seen in young children.

The clinical features that differentiate nonepileptic seizures (pseudoseizures) from epileptic form seizures are presented in the following table.

Cragar DE, Berry DT, Fakhoury TA, Cibula JE, Schmitt FA. A review of diagnostic techniques in the differential diagnosis of epileptic and nonepileptic seizures. Neuropsychol Rev 2002;12(1):31–64

Reuber M, Elger CE. Psychogenic nonepileptic seizures: review and update. Epilepsy Behav 2003;4(3): 205–216

William TH. Pseudoseizures: differential diagnosis. J Neuropsychiatr Clin Neurosci 1981;1(1):67–69

3.4 Neonatal Seizures by the Time of Onset

Neonatal seizures are seizures occurring within the first 28 days in a full-term infant and extending to the 44 completed weeks gestational age in the preterm infant. The prevalence is approximately 1.5% and overall incidence approximately 3 per 1,000 live births. The neonatal period is the most vulnerable of all periods of life for developing seizures, particularly in the first 1–2 days to the first week from birth. They may be short-lived events lasting for a few days only. However, they often signify serious malfunction of or damage to the immature brain and constitute a neurological emergency.

3.5 Neonatal Seizures

Neonatal epileptic syndromes present with different seizure types. Understanding the conceptual difference between seizure and epileptic syndrome is important.

An epileptic seizure is defined as a transient neurologic dysfunction resulting from an excessive abnormal electrical discharge of cerebral neurons. The clinical manifestations are numerous, including disturbances of consciousness, changes in emotions, changes in sensation, abnormal movements, and changes in visceral functions or behavior.

Epilepsy syndromes is a group of disorders characterized by chronic, recurrent paroxysmal changes in neurologic function caused by abnormalities in electrical activity of the brain. The 2001 International League Against Epilepsy proposed a new diagnostic scheme for epilepsy syndromes and related conditions which is described below.

1. 
   

   Benign familial neonatal seizure

   
   

   Autosomal dominant channelopathy with brief seizures within the first days of life (80% on the 2nd and 3rd day) typically in premature infants. The diagnosis is suspected when seizures occur without obvious precipitants in an otherwise normal newborn with a family history of similar seizures in the neonatal period. Prognosis is good.

   
   
2. 
   

   Early myoclonic encephalopathy

   
   

   Clinically characterized by erratic or massive myoclonus, partial seizures, tonic spasms, and a suppression-burst pattern on EEG. It is believed to have various prenatal etiologies that often remain unknown; inborn errors of metabolism and genetic disorders are sometimes found. Prognosis is poor.

   
   
3. 
   

   Ohtahara syndrome

   
   

   It is one of the earliest developing forms of epileptic encephalopathy. The main characteristics of the syndrome are tonic seizures and a suppression-burst pattern on EEG. The etiology is symptomatic, with the majority of cases associated with structural brain damage, but recent cases due to genetic mutation and metabolic abnormalities have been described. Prognosis very poor.

   
   
4. 
   

   Benign neonatal seizures (nonfamilial)

   
   

   These are characterized by a single episode of repetitive clonic seizures, mainly unilateral, often of alternating sides in a full-term, previously healthy neonate; all investigations, except EEG, are normal. Due to the tendency of the seizures to occur on the 4th–5th day of life, the term “fifth day fits” has been commonly been used.

Panayiotopoulos CP. Neonatal seizures and neonatal syndromes. Chapter 5. In: Panayiotopoulos CP ed. The Epilepsies: Seizures and Management. Oxfordshire (UK): Bladon Medical Publishing; 2005

Plounin P. Benign familial neonatal convulsions and benign idiopathic neonatal convulsions. In: Engel J jr, Pedley TA, eds. Epilepsy. A Comprehensive Textbook. Lippincott-Raven; 1997:2247–2255

Heron SE, Crossland KM, Andermann E, et al. Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet 2002;360(9336):851–852

Silverstein FS, Jensen FE. Neonatal seizures. Ann Neurol 2007;62(2):112–120

Pisani F, Sisti L, Seri S. A scoring system for early prognostic assessment after neonatal seizures. Pediatrics 2009;124(4):e580–e587

3.6 First Nonfebrile Tonic–Clonic Seizure after 2 Years of Age

1. 
   

   Viral encephalitis

   
   
   
   
   1. 
      

      Herpes simplex encephalitis

      
      
   2. 
      

      Arboviral encephalitis

      
      
      
      
      • 
        

        i. St. Louis encephalitis

        
        
      • 
        

        ii. Western and Eastern equine encephalitis

        
        
      • 
        

        iii. Japanese B encephalitis

        
        
      • 
        

        iv. California-La Crosse encephalitis

      
      
   3. 
      

      Retrovirus encephalitis (e.g., AIDS encephalitis)

      
      
   4. 
      

      Rhabdovirus encephalitis (e.g., Rabies encephalitis)

   
   
2. 
   

   Idiopathic isolated seizure

   
   
3. 
   

   Partial complex seizures with secondary generalization (any seizure originating in the cortex may discharge into the brain stem)

   
   
   
   
   1. 
      

      Benign rolandic epilepsy of childhood

      
      
   2. 
      

      Benign occipital epilepsy of childhood

      
      
   3. 
      

      Epilepsia partialis continua

   
   
4. 
   

   Progressive encephalopathy

   
   
   
   
   1. 
      

      Infectious diseases (e.g., subacute sclerosing panencephalitis)

      
      
   2. 
      

      Lysosomal enzymes disorders

      
      
      
      
      • 
        

        i. Glycoprotein disorders

        
        
      • 
        

        ii. Mucopolysaccharidoses types II and VII

        
        
      • 
        

        iii. Sphingolipidoses

      
      
   3. 
      

      Genetic disorders of gray matter

      
      
      
      
      • 
        

        i. Huntington disease

        
        
      • 
        

        ii. Mitochondrial disorders

        
        
      • 
        

        iii. Xeroderma pigmentosum

      
      
   4. 
      

      Genetic disorders of white matter

      
      
      
      
      • 
        

        i. Alexander disease

        
        
      • 
        

        ii. Adrenoleukodystrophy

Pohlmann-Eden B, Beghi E, Camfield C, Camfield P. The first seizure and its management in adults and children. BMJ 2006;332(7537):339–342

3.7 Posttraumatic Epilepsy

If a case of posttraumatic epilepsy (PTE) demonstrates atypical features and the seizures continue despite treatment, the possibility of pseudoseizures should be considered. In patients with refractory PTE following moderate traumatic brain injury, about 20–30% proved to have been misdiagnosed and were actually having psychogenic attacks. This percentage is similar to that in patients with seizures after nontraumatic brain injury.

Therefore, the diagnosis should be verified by video-EEG monitoring which shows that the nature of the seizures is psychogenic rather than epileptic.

3.8 Causes of Confusion and Restlessness

1. 
   

   Epileptic (e.g., partial complex seizures, absence type seizures)

   
   
2. 
   

   Metabolic and systemic disorders

   
   
   
   
   1. 
      

      Osmolality disorders (e.g., hyponatremia, hypoglycemia)

      
      
   2. 
      

      Endocrine disorders (e.g., adrenal insufficiency, parathyroid and thyroid disorders)

      
      
   3. 
      

      Hepatic encephalopathy

      
      
   4. 
      

      Metabolic disorders (e.g., carnitine deficiency, urea cycle and pyruvate disorders)

      
      
   5. 
      

      Renal disease (e.g., hypertensive and uremic encephalopathy)

   
   
3. 
   

   Infectious disorders

   
   
   
   
   1. 
      

      Bacterial infections (e.g., meningitis, cat scratch disease)

      
      
   2. 
      

      Rickettsial infections (e.g., Lyme disease)

      
      
   3. 
      

      Viral infections (e.g., Herpes simplex, arboviruses, measles and postinfectious encephalitis, Reye syndrome)

   
   
4. 
   

   Vascular

   
   
   
   
   1. 
      

      Congestive heart failure

      
      
   2. 
      

      Subarachnoid hemorrhage

      
      
   3. 
      

      Embolic infarction

      
      
   4. 
      

      Vasculitis and connective tissue disorders

      
      
   5. 
      

      Migraine

   
   
5. 
   

   Toxic

   
   
   
   
   1. 
      

      Substance abuse

      
      
   2. 
      

      Prescription drugs

      
      
   3. 
      

      Toxins

   
   
6. 
   

   Psychogenic (e.g., panic disorder, schizophrenia)

   
   
7. 
   

   Postoperative (most common)

   
   
   
   
   1. 
      

      Cerebrovascular disease

      
      
   2. 
      

      Drugs, delirium tremens

      
      
   3. 
      

      Chest infection or atelectasis

      
      
   4. 
      

      Renal infection

      
      
   5. 
      

      Abdominal sepsis, superficial or deep

      
      
   6. 
      

      Over-full bladder or rectum

3.9 Hypotonic Infant or “Floppy Baby or Infant”

The term “floppy baby or infant” is used to denote an infant with poor muscle tone affecting the limbs, trunk, and the craniofacial musculature (▶Fig. 3.1). The condition is usually evident at birth or is identified during early life as poor musculature results in an inability to maintain normal posture during movement and rest.

Lesions at any level of the nervous system, including upper and lower motor units, can cause hypotonia. Hypotonia combined with severe muscle weakness usually is associated with lower motor neuron disease, including diseases affecting anterior horn cells of the spinal cord, peripheral nerves, neuromuscular junctions, and muscles. Hypotonia without obvious weakness often points to diseases of the central nervous system (CNS) as a result of a perinatal insult or may manifest later in infants with mental retardation or cerebral palsy. It may be a manifestation of a connective tissue disorder, chromosomal disease, or those involving metabolic, endocrine, or nutritional problems. It may also be an incidental and nonspecific feature of an acutely ill child and it is completely physiologic in the premature infant.

Irrespective of the cause, the floppy infant is likely to present a somewhat similar clinical picture, which one usually recognizes on the basis of three clinical signs: (a) bizarre or unusual posture, (b) diminished resistance of the joints to passive movements, and (c) increased range of joint movement. In the newborn period, the infant usually presents with the above features, together with a paucity of active movement; the older infant usually presents with delay in motor milestones. Central causes account for 60–80% of cases and that the diagnosis can usually be made by a careful history and examination. However, there may be a mixed picture. Infants with a peripheral cause for their hypotonia may be at increased risk for problems during labor, delivery, and resuscitation and develop hypoxic ischemic encephalopathy.

3.10 Causes of “Floppy” Infant

1. 
   

   Systemic disease

   
   

   The most important and by far the most frequent cause of hypotonia in the newborn infant is systemic disease that influences the entire CNS (brain/brain stem) diffusely to cause hypotonia. The most frequent examples include:

   
   
   
   
   1. 
      

      Congestive heart failure (significant congenital heart disease)

      
      
   2. 
      

      Sepsis

      
      
   3. 
      

      Hypoxic-ischemic insult (after they regain consciousness hypotonia persists for months, sometimes until they begin to get increased tone and reflexes and become spastic after the first 2–3 months.

   
   
2. 
   

   Cerebral hypotonia

   
   

   Clues of diagnosis are:

   
   
   
   
   1. 
      

      Other brain dysfunction,

      
      
   2. 
      

      dysmorphic features,

      
      
   3. 
      

      fisting of the hands,

      
      
   4. 
      

      malformations of other organs,

      
      
   5. 
      

      movement through postural reflexes,

      
      
   6. 
      

      normal or brisk tendon reflexes, scissoring on vertical suspension.

      
      
      
      
      • 
        

        i. Benign congenital hypotonia: Hypotonic at birth, but later on have normal tone and increased incidence of cerebral abnormalities, e.g., retardation, learning difficulties, and other disabilities.

        
        
      • 
        

        ii. Chromosomal disorders

        
        
        
        
        • 
          

          Trisomy

          
          
        • 
          

          Prader–Willi syndrome: Deletion of the long arm of chromosome 15 causing hypotonia, mental retardation, obesity, short stature, and hypogonadism

        
        
      • 
        

        iii. Cerebral dysgenesis: It is suspected when hypotonia is associated with malformations in other organs or abnormalities in the size and shape of the head

        
        
      • 
        

        iv. Peroxisomal dysfu nctions

        
        
        
        
        • 
          

          Cerebrohepatorenal syndrome (Zellweger syndrome): Severe hypotonia, arthrogryposis, dysmorphic features, seizures. Death from aspiration, gastrointestinal bleeding, or liver failure within 1 year.

          
          
        • 
          

          Neonatal adrenoleukodystrophy: X-linked characterized by hypotonia, dysmorphia, failure to thrive, seizures, retardation, and spasticity. Death in early childhood.

          
          
        • 
          

          Infantile Refsum disease

        
        
      • 
        

        v. Genetic disorders

        
        
        
        
        • 
          

          Familial dysautonomia (Riley–Day syndrome): Autosomal recessive hypotonia from disturbances in the brain, dorsal root ganglia, and the peripheral nerves.

          
          
        • 
          

          Oculocerebrorenal syndrome (Lowe syndrome): X-linked recessive hypotonia, hyporeflexia, cataracts, and glaucoma. Normal life span.

   
   
3. 
   

   Spinal cord disorders

   
   
   
   
   1. 
      

      Hypoxic-ischemic myelopathy: In severe perinatal asphyxia causing hypotonia and areflexia

      
      
   2. 
      

      Spinal cord injury: Cervical spinal cord injury occurs exclusively during vaginal delivery; approximately 75% with breech presentation and 25% with cephalic presentation. Sphincter dysfunction and a sensory level at mid chest suggest myelopathy.

   
   
4. 
   

   Motor unit disorders

   
   

   Clues to diagnosis are:

   
   
   
   
   1. 
      

      Absent or depressed tendon reflexes,

      
      
   2. 
      

      Failure of movement on postural reflexes,

      
      
   3. 
      

      Fasciculations,

      
      
   4. 
      

      Muscle atrophy,

      
      
   5. 
      

      No abnormalities of other organs.

      
      
      
      
      • 
        

        i. Spinal muscular atrophies

        
        

        Genetic degeneration of anterior horn cells in the spinal cord and motor nuclei of the brain stem.

        
        
        
        
        • 
          

          Acute infantile spinal muscular dystrophy (Werdnig–Hoffmann disease)

          
          
        • 
          

          Chronic infantile spinal muscular dystrophy

          
          
        • 
          

          Infantile neuronal degeneration

          
          
        • 
          

          Neurogenic arthrogryposis

        
        
      • 
        

        ii. Polyneuropathies

        
        
        
        
        • 
          

          Axonal

          
          
          
          
          • 
            

            Familial dysautonomia

            
            
          • 
            

            Hereditary motor-sensory neuropathy type II

            
            
          • 
            

            Idiopathic with encephalopathy

            
            
          • 
            

            Infantile neuronal degeneration

          
          
        • 
          

          Demyelinating

          
          
          
          
          • 
            

            Acute inflammatory (Guillain-Barre syndrome)

            
            
          • 
            

            Congenital hypomyelinating neuropathy

            
            
          • 
            

            Hereditary motor-sensory neuropathies, type I and type III

            
            
          • 
            

            Metachromatic leukodystrophy

        
        
      • 
        

        iii. Disorders of neuromuscular transmission

        
        
        
        
        • 
          

          Infantile botulism

          
          
        • 
          

          Familial infantile myasthenia

          
          
        • 
          

          Transitory neonatal myasthenia

        
        
      • 
        

        iv. Congenital myopathies (fiber-type disproportion)

        
        
        
        
        • 
          

          Central core disease: Tightly packed myofibrils in the center of all type I fibers are undergoing degeneration.

          
          
        • 
          

          Fiber-type disproportion myopathy: Predominance of type I fiber and hypotrophy

          
          
        • 
          

          Myotubular myopathy: Predominance of type I fiber and hypotrophy, many internal nuclei, and a central core of increased oxidative enzyme and decreased myosin ATPase activity

          
          
        • 
          

          Nemaline myopathy: Multiple rodlike particles are present within most or all muscle fibers.

        
        
      • 
        

        v. Muscular dystrophies

        
        
        
        
        • 
          

          Congenital muscular dystrophy: Various size fibers present nucleation, extensive fibrosis, and proliferation of adipose tissue, regeneration and degeneration, and thickening of the muscle spindle capsule.

          
          
          
          
          • 
            

            Fukuyama type

            
            
          • 
            

            Leukodystrophy

            
            
          • 
            

            Cerebro-ocular dysplasia

          
          
        • 
          

          Neonatal myopathic dystrophy: Maturational arrest in muscles surrounding a fixed joint, and predominance of type II fibers.

        
        
      • 
        

        vi. Metabolic myopathies

        
        
        
        
        • 
          

          Acid maltase deficiency (Pompe’s disease)

          
          
        • 
          

          Carnitine deficiency

          
          
        • 
          

          Cytochrome-c-oxidase deficiency

          
          
        • 
          

          Phosphofructokinase deficiency

          
          
        • 
          

          Phosphorylase deficiency

        
        
      • 
        

        vii. Infantile myositis: Diffuse inflammation and proliferation of connective tissue, and muscle fiber degeneration.

        
        
      • 
        

        viii. Endocrine myopathies

        
        
        
        
        • 
          

          Hyper/hypothyroidism

          
          
        • 
          

          Hyper/hypoparathyroidism

          
          
        • 
          

          Hyper/hypoadrenalism

3.11 Precocious Puberty or Accelerated Sexual Maturity

Precocious puberty is the appearance of signs of pubertal development at an abnormally early age (▶Fig. 3.2). In girls, this age has traditionally been considered to be 8 years, although guidelines from the United States have recommended that puberty be considered precocious only with appearance of breast development or pubic hair before 7 years of age in white girls and before 6 years of age in black girls. In boys, the onset of puberty before 9 years of age is considered to be precocious. The female-to-male ratio is 10:1. Precocious puberty is often a benign central process in girls but precocious puberty is rarely idiopathic in boys and early signs of puberty in boys are a particular cause for concern.

Precocious puberty can be divided into two distinct categories.

1. 
   

   Gonadotrophin-dependent precocious puberty (central precocious puberty, (CPP) “true”): This involves the premature activation of the hypothalamic–pituitary–gonadal (HPG) axis. Most children (especially girls) suspected of having CPP do not have any specific abnormality but lie at one end of the normal distribution curve.

   
   

   The causes may be:

   
   
   
   
   1. 
      

      Idiopathic (sporadic or familial)

      
      
   2. 
      

      CNS abnormalities or lesions

      
      
      
      
      • 
        

        i. Hypothalamic hamartomas

        
        
      • 
        

        ii. Tumors: astrocytoma, craniopharyngioma, ependymoma, glioma Germinoma, pineal tumors, human chorionic gonadotrophin (HCG)-secreting tumors, hypothalamic teratomas

        
        
      • 
        

        iii. Congenital malformations: arachnoid cyst, suprasellar cyst, phakomatosis, hydrocephalus (+ spina bifida), septo-optic dysplasia

        
        
      • 
        

        iv. Acquired disease: Inflammatory CNS disease, abscess, radiation, chemotherapy, trauma, ischemia, surgery

        
        
      • 
        

        v. Dysmorphic syndromes: Williams–Beuren syndrome, Klinefelter syndrome (rare)

        
        
      • 
        

        vi. Prolonged exposure to sex steroids: Congenital adrenal hyperplasia, sex steroid-producing tumors

      
      
   3. 
      

      Absence of CNS abnormalities, the causes of early normal puberty include:

      
      
      
      
      • 
        

        i. Genetic: Early puberty is familial and autosomal dominant

        
        
      • 
        

        ii. Russell–Silver syndrome

        
        
      • 
        

        iii. McCune–Albright syndrome

        
        
      • 
        

        iv. Hypothyroidism

        
        
      • 
        

        v. Obesity: in girls, but not in boys, early puberty is associated with increase in body mass index (BMI).

   
   
2. 
   

   Gonadotrophin-independent precocious puberty (or precocious pseudopuberty): In this, the presence of sex steroids is independent of pituitary gonadotrophin release. This accounts for about 20% of cases of precocious puberty. The gonad matures independently of gonadotrophin-releasing hormone (GnRH) stimulation and levels of testosterone and estradiol, luteinizing hormone (LH) and follicle-stimulating hormone are usually at pubertal levels (in the absence of gonadotrophin pulsatility). There is a flat GnRH response and no response to treatment with GnRH analogues.

   
   

   The causes may be:

   
   
   
   
   1. 
      

      Adrenal disorders

      
      
      
      
      • 
        

        i. Adrenal adenoma

        
        
      • 
        

        ii. Adrenal carcinoma

        
        
      • 
        

        iii. Congenital adrenal hyperplasia

      
      
   2. 
      

      Ovarian disorders: can cause masculinization or feminization

      
      
      
      
      • 
        

        i. Granulosa cell tumor

        
        
      • 
        

        ii. Theca cell tumors

        
        
      • 
        

        iii. Other estrogen-secreting tumors: teratoma, teratocarcinoma, dysgerminoma, luteoma, mixed cell tumor, lipoid tumor

        
        
      • 
        

        iv. Sex-cord or Sertoli-cell tumor of the ovary, and aromatase activity in Peutz–Jeghers syndrome

        
        
      • 
        

        v. McCune–Albright syndrome (ovarian cysts)

        
        
      • 
        

        vi. Autonomous isolated ovarian cysts

      
      
   3. 
      

      Testicular disorders

      
      
      
      
      • 
        

        i. Leydig cell adenoma

        
        
      • 
        

        ii. Constitutively activating LH receptor mutations (male-limited precocious puberty, i.e., testotoxicosis)

      
      
   4. 
      

      Human chorionic gonadotrophin (HCG)-secreting tumors

      
      
      
      
      • 
        

        i. Dysgerminoma

        
        
      • 
        

        ii. Teratoma

        
        
      • 
        

        iii. Chorioepithelioma

        
        
      • 
        

        iv. Choriocarcinoma

        
        
      • 
        

        v. Hepatoblastoma

        
        
      • 
        

        vi. Pinealoma

      
      
   5. 
      

      Exogenous

      
      
      
      
      • 
        

        i. Sex steroid exposure: pills (estrogens, anabolics), food additives, cosmetics, creams, etc.

Muir A. Precocious puberty. Pediatr Rev 2006;27(10):373–381

Kaplowitz P. Precocious puberty: update on secular trends, definitions, diagnosis, and treatment. Adv Pediatr 2004;51:37–62

3.12 Arthrogryposis

Arthrogryposis multiplex congenita is a collective term applied to a very large number of different syndromes characterized by nonprogressive, multiple joint contractures present at birth. (▶Fig. 3.3) The joints usually develop normally in early embryonic life but as gestation progresses, movements are required to facilitate normal development. Abnormalities, such as neurological or connective-tissue disorders or physical restriction, lead to this condition. The basic cause is fetal akinesia. The underlying cause can be environmental (lack of ability to move) or genetic (single gene conditions). The muscles involved are partially or completely replaced by fat and fibrous tissue. The most common form, accounting for 40% of cases, is amyoplasia (A = no, myo = muscle, plasia = growth).

Related posts:

4 Cranial Nerve Disorders 5 Neuro-Ophthalmology 2 Neuroradiology 9 Spinal Disorders 11 Movement Disorders 12 Neurotrauma

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