Clinical course
The boy was born from second pregnancy, second birth, born by Caesarean section (due to polyhydramnios, fetal heart rate anomalies in CTG) in 38th week of pregnancy with birth weight 3960g, head circumference 37cm (> 97th percentile). In the Apgar scale, he received 7/7/10/10 points. Irregular breathing, pale grey skin, and increased muscle tone were noted; saturation of 65% and mild metabolic acidosis in umbilical cord blood. Mechanical ventilation was used to stabilize the child’s condition. During pregnancy, the mother was diagnosed with hypothyroidism, treated with levothyroxine; fetal hiccups were noted. The family history for miscarriages, deaths in early childhood, and neurological and metabolic diseases were negative. The child’s parents are unrelated; the proband has a healthy, 2-yr-old sister.
Physical examination revealed facial dysmorphism (as coarse features with puffy cheeks, bitemporal narrowing, deep-set eyes, long philtrum, dysplastic auricles), long and overlapping fingers, large feet, pectus excavatum, swelling of the eyelids and lumbosacral region. At 30 minutes after the birth, deterioration in the general condition, grunting drops in desaturation were observed with subsequent diagnosis of congenital pneumonia. Difficulties in feeding (lack of sucking), muscular tension disorders, epileptic seizures, and breathing difficulties with an abnormal crying further complicated perinatal period. Convulsions with drops in saturation occurred on the first day of life. Despite the phenobarbital implementation, polymorphic epileptic seizures, limb myoclonus, breathing disorders, sometimes with desaturation, were still observed. Within the following days, the child became inactive and flaccid. Abnormal spontaneous movements of the extremities were observed, as nonrhythmic waving, pedaling, and increased muscle tone, especially in upper extremities. Reduced muscular tension was accompanied by areflexia. Since seizures were still uncontrolled, levetiracetam was additionally introduced to the treatment with initially good effect. During the hospitalization, muscle tone gradually increased, and elbow and knee joints contractures appeared.
In the second month of life, the child gradually became more reactive, but still presented clearly an impoverished spontaneous motor activity. At times, the boy opened his eyes, but with no eye contact and did not follow with his eyes. He was fed with a nasogastric tube. Physically, the skin was pale, pasty, head circumference was still above 97th percentile, and prominent cranial sutures were noted. The axial hypotonia and lower limb spasticity were observed; tendon hyperreflexia appeared. In the neurological examination, the traction test was negative, no sole reflex on both sides, no Babinski sign bilaterally, weak grasping reflexes, no Moro reflex. Periodically restless, crying, and hyperekplexia were observed, as well as epileptic seizures, mainly myoclonic. Thus, in addition to phenobarbital and levetiracetam, valproic acid was later introduced. Due to tachycardia, propranolol was included in the treatment. Hypothyroidism requiring substitution with levothyroxine was also diagnosed. Because of severe and worsening clinical condition, the child was transferred to a home hospice.