Background

and Purpose: Postnatal progressive microcephaly, with seizures and brain atrophy (OMIM # 613668) is a rare disorder caused by a homozygous founder missense mutation c.1112T>C (p.L371P) in the MED17 gene on chromosome 11 that was identified in 2010 in Caucasus Jewish families. The present study aimed to delineate the phenotype and developmental outcomes in patients diagnosed with this mutation to date.

Methods

We conducted a medical charts review to collect the clinical, laboratory and neuroimaging findings in patients from several unrelated families of Caucasus-Jewish origin, who were diagnosed with the same homozygous c.1112T>C MED17 mutation.

Results

The study cohort, including the previously reported patients, comprised 10 males and 5 females from 11 families. All subjects had at birth a normal head circumference, which steeply declined to -6SD within a few months. None of the patients achieved developmental milestones. All patients had progressive spasticity and were wheelchair bound due to spastic quadriplegia. All of them eventually developed profound intellectual disability. Epilepsy of varied severity was present in all patients. Most patients required enteral feeding due to aspirations. Eight patients died before puberty (age range 2–13 years). Brain MRI showed marked cerebral atrophy and early prominent cerebellar atrophy (vermian > hemispheres) accompanied by pontine ventral flattening.

Conclusions

The founder c.1112T>C mutation in MED17 gene is expressed by a unique and homogeneous clinical phenotype with distinctive MRI findings. This mutation should be considered in patients of Caucasus-Jewish ancestry presenting with clinical features and a MRI pattern of progressive cerebral and cerebellar atrophy.

中文翻译：

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高加索犹太人家庭中与MED17相关疾病表型的描述

背景

目的：产后进行性小头畸形，癫痫发作和脑萎缩（OMIM ＃ 613668）是一种罕见疾病，由2010年发现的11号染色体MED17基因纯合创始人错义突变c.1112T> C（p.L371P）引起。在高加索犹太家庭中。本研究旨在描述迄今诊断为该突变的患者的表型和发育结局。

方法

我们进行了医学图表审查，以收集来自高加索-犹太血统的几个无关家庭的患者的临床，实验室和神经影像学检查结果，这些患者被诊断出具有相同的纯合c.1112T> C MED17突变。

结果

该研究队列包括先前报道的患者，包括来自11个家庭的10位男性和5位女性。所有受试者出生时头围均正常，在几个月内陡然下降至-6SD。没有患者达到发展里程碑。所有患者均进行性痉挛，由于痉挛性四肢瘫痪而被轮椅束缚。他们最终都发展出了深刻的智力障碍。所有患者均出现严重程度不同的癫痫病。由于抽吸，大多数患者需要肠内喂养。八名患者在青春期之前死亡（年龄2-13岁）。脑部MRI显示明显的脑萎缩和早期显着的小脑萎缩（vermian>半球），伴有桥脑腹板变平。

结论

MED17基因的创始人c.1112T> C突变由具有独特MRI表现的独特且均一的临床表型表达。具有临床特征和进行性脑和小脑萎缩的MRI模式的高加索犹太血统患者应考虑这种突变。