2018年 · 第56卷第11期

Intellectual disability is a type of neurodevelopmental disorder with complex etiological spectrum and high clinical and genetic heterogeneity in childhood. It is also a relatively common cause of disability in childhood, with a global prevalence of about 1% and a prevalence of severe intellectual disability of about 0.6%^[1]The prevalence rate of intellectual disability in China is 0.43% ~0.96%^[2]。 The basic clinical characteristics of intellectual disability are the defects of intelligence and adaptability that appear before the age of 18, but the manifestations are complex and diverse, and heterogeneous. Early identification, etiological diagnosis and related targeted treatment, early education and training can significantly improve the long-term functional prognosis of children. In the past 10 years, the identification and management level of intellectual disabilities in China has gradually improved, but there is still a lack of standardized diagnosis process and treatment management guidelines. Most pediatricians have insufficient identification of early manifestations of children, and the screening and diagnosis process lacks unified standards. Therefore, the Neurology Group of the Pediatrics Branch of the Chinese Medical Association and the Children's Neurology Professional Committee of the Neurology Branch of the Chinese Medical Doctors Association released the "Expert Consensus on Diagnostic Strategies for the Cause of Children's Intellectual Disability or General Developmental Delay" for the first time.^[3]It will further standardize the diagnosis process of children with intellectual disabilities or general developmental delay, and promote the improvement of early etiological diagnosis, early intervention, prognosis assessment and genetic counseling of intellectual disabilities.

Intellectual disability or general developmental retardation is a serious harm to children's physical and mental health. It is one of the major birth defects and has become a worldwide social problem. Intellectual disability or general developmental delay is a disorder that occurs before the age of 18 and is manifested by significant limitations in intellectual function and adaptive behavior^[1]。 The term intellectual disability is commonly applied to children ≥5 years of age, while global developmental delay is specifically applied to children younger than 5 years of age who are unable to undergo systemic assessment of intellectual function. According to its severity, it can be divided into four grades: mild (IQ 50-70), moderate (IQ 35-50), severe (IQ 20-35) and extremely severe (IQ<20）。 The global prevalence of intellectual disabilities is approximately 1%, and rates are higher in low-and middle-income countries, with an estimated total of 150 million people with intellectual disabilities worldwide. In addition to harm to individuals and families, intellectual disabilities also incur enormous medical expenses and social costs, with U.S. studies estimating the total lifetime cost of patients born in 2000 alone to be as high as $51.2 billion^[2]。 With the rapid development of society and the increasingly fierce competition for talents, all countries attach great importance to children's intellectual disabilities, and great progress has been made in the research of etiology, prevention, treatment and social security. The research results are of great significance for improving the quality of the population and increasing its core competitiveness.

Intellectual disability or general developmental retardation is a large class of neurodevelopmental disorders with high clinical and genetic heterogeneity, which often combine with autism spectrum disorder, attention deficit hyperactivity disorder and other mental behavior disorders. Intellectual disability or general developmental delay is one of the leading causes of childhood disability worldwide^[1]Its etiology is complex, involving many factors such as genetics and environment, and its clinical manifestations are complex and diverse, with strong heterogeneity. There are still many problems and lack of standards in the domestic etiology diagnosis process. Therefore, the Neurology Group of Pediatrics Branch of Chinese Medical Association and the Children's Neurology Professional Committee of Neurology Branch of Chinese Medical Doctors Association set up an expert group to discuss and put forward the etiology and diagnosis strategy of children with intellectual disability or general developmental delay. Chinese expert consensus, with a view to standardizing the diagnosis process of children with intellectual disability or general developmental delay, so as to facilitate early clarification of the etiology and early intervention, avoid repeated over-examination, and provide more accurate prognosis assessment and genetic counseling.

Example 1Male, 5 years old at the time of his first visit (in Peking University First Hospital in 2006). The child was the first child of his mother, and was born by cesarean section at full term. The birth weight was 4,000 g. He could cry after birth and could not kick the quilt. He looked up at the age of 2 and sat alone at the age of 5. He had been unable to stand or walk alone. Can recognize people, and at the age of 5 and a half, he has conscious expression of simple language. One febrile convulsion occurred at the age of 4 and a half, which was manifested by upward turning of both eyes and stiffness of limbs after fever, which lasted for tens of seconds to relieve. Physical examination at the age of 5: myopathic face, poor eye movement, high palatal arch, pseudohypertrophy of forearm muscles and lower limb calf gastrocnemius muscle, obvious knee contracture, no abnormalities in cardiopulmonary and abdominal examination, reduced muscle tone, decreased muscle strength, obvious proximal end, bilateral knee tendon reflex not drawn out, and negative Pap sign. Auxiliary examination: Serum creatine kinase: 11 600 U/L (at 1 year old), cranial magnetic resonance imaging (MRI) showed: multiple cerebellar gyrus, cerebellar dysplasia, white matter changes. Compound heterozygous mutations found in FKTN gene assay (reported): c.139C>T, p.R47X; c. 4375_4376insAB185332.1. Congenital muscular dystrophy of Fukuyama type was diagnosed and not treated with medication. After 10 years of age, he was given levetiracetam with repeated non-febrile convulsions. The medication was irregular and the seizure control was unsatisfactory. When the child was 12 years old, the EEG showed: the waking period was low-amplitude 6-10 Hz mixed wave or activity, intermittent extensive medium-amplitude 6-7 Hz θ activity, and sometimes intermittent low-amplitude 12-15 Hz fast wave activity; Before the sleep period, the head is the main spindle-like wave protruding widely, sometimes the wave amplitude is high and the wave shape is pointed (Figure 1）。 Follow-up: The child died at 13 years old after suffering from severe pneumonia.

The child, 2 years old and 7 months old, went to the Pediatric Hospital affiliated to Fudan University in August 2015 because of "big head and late speech". When the child was first diagnosed, he had meaningless pronunciation, eye contact and joint attention, was insensitive to naming, couldn't use fingers, was attached to his parents, and would play slides with children, but lacked communication and interaction. Before the age of 2, he had no communication with strangers at all, occasionally shared behaviors, often kissed and hugged. Clinical diagnosis of "mental retardation". The child was the fourth and second birth of the mother, born naturally at full term, with a birth weight of 2.8 kg and a length of 50 cm. The head circumference increased rapidly at the age of 4~6 months, up to 3 cm/month; 18 months old will walk alone. History of convulsions, history of epilepsy, history of severe head trauma, neurological infections, and severe congenital diseases are denied. Her mother's fetal heart rate was slowed in the second trimester of pregnancy, and she was treated with oxygen for 1 week. She was depressed throughout her pregnancy. Spontaneous abortion in the late pregnancy of the first child, premature rupture of membranes and spontaneous abortion in the second child, and accidental death by choking in the neonatal period of the third child. The mother is 23 years old and the father is 22 years old. He is not a close relative. Mother's head circumference 62.6 cm (>P₉₇), 4~5 years old only had active language, now poor eye contact, strong timbre, difficulty in communication, accompanied by forehead papules, and hemangiomas on both sides of the calves.

The 11-year-old male was admitted to the Children's Hospital affiliated to the Capital Institute of Pediatrics in October 2017 because of "diagnosis of acute myeloid leukemia for 1 year and blood in the stool for 10 days". The child developed pale complexion with dizziness, headache and abdominal discomfort more than 1 year before admission, and gradually worsened. The perfect blood routine in the local hospital showed that white blood cells were 11.66×10⁹/L, hemoglobin 94 g/L, platelets 110×10⁹/L, abdominal ultrasound showed hepatosplenomegaly, bone marrow puncture showed blastocytes 0.064, considering the possibility of acute myelomonocytic leukemia, no abnormal chromosome clones were found, immunotyping showed malignant myeloid naive cells 0.103, expressing CD34, CD117, HLA-DR, CD33, CD13, CD11c, CD96, CD38, partially expressing CD9, and gene mutations: KRAS G12D mutation positive, NRAS G13R mutation positive, WT1R369Afs*16 and S381Vfs*4 mutation positive. Oral imatinib 0.1 g/d was started 1 year ago, and bone marrow puncture revealed myeloid naive cells 0.455 1 month later. After that, oral traditional Chinese medicine treatment was interrupted for more than 2 months. Reexamination of bone marrow puncture revealed myeloid naive cells + naive mononuclear 0.225, and immunotyping: abnormal cells 0.215. In April 2017, HAG regimen (homoharringtonine + cytarabine + granulocyte colony stimulating factor) chemotherapy was performed. Reexamination of bone marrow puncture revealed abnormal myeloid naive cells 0.027. Considering that the treatment is effective, CAG (cytarabine + arubicin + granulocyte colony stimulating factor) regimen chemotherapy was given. Reexamination of bone marrow puncture after chemotherapy revealed malignant cells 0.230. He was given decitabine in combination with CAG regimen chemotherapy (decitabine + arubicin + cytarabine + granulocyte colony stimulating factor) in August 2017. One week after chemotherapy, a large amount of dark red bloody stool, 1 500~2 000 ml/d, blood routine showed white blood cells 0.96×10⁹/L, hemoglobin 79 g/L, platelets 30×10⁹/L, given active hemostasis, symptomatic blood transfusion to supplement coagulation factors and other treatments, there was still intermittent blood in the stool, for further diagnosis and treatment, transferred to our department for colonoscopy. Family history: Parents are not intimate married, and there is no history of related diseases in the family.

The 6-month-old child was admitted to the Children's Hospital affiliated to Nanjing Medical University in December 2017 due to "fever for 2 days with frequent convulsions for 1 day". The child developed fever 2 days ago, with a maximum of 39.7℃, accompanied by vomiting twice, which was stomach content, non-jetting, no coffee-colored substance, no rash, convulsions, and was in good spirits. He took "ibuprofen suspension and pediatric Chaigui granules" orally by himself, and the vomiting was relieved, but he still had fever. He was irritable, pale and sweaty that night. No abnormalities were found in the routine blood test of the local hospital. He was proposed to be diagnosed with "upper respiratory tract infection" and given "amoxicillin, pediatric paracetamol and xanamin granules, and tempeh Qiao granules" orally. The effect was not good, the appetite was not good, and the blood sugar was measured at 0.3 mmol/L, and the symptomatic treatment such as infusion was given (details are unknown). The liver function was obviously abnormal (the first time,Table 1), transferred to the local First People's Hospital for further treatment. During the transfer, he had 3 convulsions. The first 2 times were both eyes oblique to one side, foaming at the mouth, pale complexion, loss of consciousness, lasting for several minutes, and relieved by itself. The convulsions were 15~20 minutes apart. The third time, the convulsions were severe and could not be relieved. After stopping the convulsions, he was admitted to the intensive care unit (ICU) and was diagnosed with Reye's syndrome. He was treated with "mannitol" for dehydration to reduce intracranial pressure, "compound glycyrrhizin" for liver protection, "ceftriaxone" for anti-infection, "lumina" for calming the convulsions, and maintaining blood sugar. The child still had poor response and drowsiness, so he was transferred to our hospital for further treatment. The child was the first birth of her mother, born by cesarean section at full term, with a birth weight of 3.0 kg, and no history of birth injury or asphyxia. Breastfeeding after birth, add complementary food on time. Previous health, healthy parents, non-consanguineous marriage, no history of hereditary diseases in the family.

shared decision making (SDM) has been widely recognized and valued worldwide since it was first proposed in 1982. People from all walks of life have made various efforts and explorations to better implement SDM. Although there are still various problems in the implementation of SDM, its importance and necessity are undoubted. In the past 10 years, more and more western countries have begun to pay attention to the implementation of SDM in the field of pediatrics, emphasizing the joint participation of children and parents in clinical decision-making. In China, there are only a handful of studies on SDM, and they are focused on the adult field. The current application of SDM in pediatrics is reviewed, so that more medical workers in pediatrics are aware of and willing to participate in and implement SDM.

The concept of real-world clinical research is spreading more and more widely, and a large number of clinical researchers consider using existing clinical data to carry out real-world clinical research. This can quickly accumulate research resources, with high efficiency and large amount of data, and can ensure that data and information come from the clinical real world. Especially in the field of pediatric clinical research, prospective and experimental research is difficult to carry out and faces many ethical challenges. It is more advantageous to use existing data to carry out research.