Verloes Alain, Ruaud Lyse, Drunat Séverine, Passemard Sandrine
Genetics Department, APHP-Robert Debré University Hospital;, Université de Paris, Paris, France
Genetics Department, APHP-Robert Debré University Hospital, Paris, France
In primary microcephaly (-MCPH), microcephaly (occipitofrontal circumference [OFC] ≥2 standard deviations below the mean) is usually present at birth, but in some instances becomes evident later in the first year of life. Growth is otherwise normal. Except for brain malformations in most affected individuals, no other congenital malformations are observed. Central nervous system involvement can include delayed motor development, mild-to-severe intellectual disability (ID), behavior problems, epilepsy, spasticity, and ataxia.
DIAGNOSIS/TESTING: The diagnosis of -MCPH is established in a proband with suggestive clinical findings and biallelic pathogenic variants in identified by molecular genetic testing.
Treatment is symptomatic. Care by a multidisciplinary team (often including a pediatric neurologist, developmental pediatrician, speech-language pathologist, occupational and physical therapist, medical geneticist, and social worker) is recommended. Follow up at each visit to assess: neurologic manifestations and response to medications for those with seizures; developmental progress and educational needs; speech-language development; behavior; physical therapy / occupational therapy needs; and social support.
-MCPH is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing, and preimplantation genetic testing are possible.
在原发性小头畸形（-MCPH）中，小头畸形（枕额周长[OFC]比平均值低≥2个标准差）通常在出生时就存在，但在某些情况下，在出生后的第一年后期才会明显。其他方面生长正常。除了大多数受影响个体存在脑畸形外，未观察到其他先天性畸形。中枢神经系统受累可包括运动发育迟缓、轻度至重度智力残疾（ID）、行为问题、癫痫、痉挛和共济失调。
诊断/检测：-MCPH的诊断通过分子遗传学检测在具有提示性临床发现和双等位基因致病变异的先证者中确立。
治疗为对症治疗。建议由多学科团队（通常包括儿科神经科医生、发育儿科医生、言语语言病理学家、职业和物理治疗师、医学遗传学家和社会工作者）进行护理。每次就诊时进行随访以评估：癫痫患者的神经系统表现和对药物的反应；发育进展和教育需求；言语语言发育；行为；物理治疗/职业治疗需求；以及社会支持。
-MCPH以常染色体隐性方式遗传。如果已知父母双方均为致病变异的杂合子，受影响个体的每个同胞在受孕时有25%的几率受影响，50%的几率为无症状携带者，25%的几率未受影响且不是携带者。一旦在受影响的家庭成员中确定了致病变异，就可以对有风险的亲属进行携带者检测、产前检测和植入前基因检测。
