Miller-Dieker syndrome (MDS), is a disorder with abnormal neuronal migration during brain development due to an underlying deletion at chromosome 17p13.3 [1]. This rare disease features classic lissencephaly (smooth brain), which is characterized by agyria (absence of brain convolutions) or frontal pachygyria (few brain convolutions) [1]. MDS also consists of microcephaly and profound facial dysmorphisms such as a prominent forehead, bitemporal hollowing, down-slanting palpebral fissures, short nose accompanied by upturned nares, protuberant upper lip, downturned vermillion border, and micrognathia [2] [3]. Occasionally, other anomalies like congenital heart malformations, genitourinary defects, and omphalocele may also be present [4] [5].

MDS is associated with a very poor prognosis. Affected children have severe developmental retardation and are at risk of dying within a few years of life [2] [3]. Complications include severe neurologic and mental delay, epilepsy, growth restriction, as well as trouble with feeding [2] [6].

• Fishing

  This was subsequently confirmed by fluorescence in situ hybridization (FISH), but not by conventional cytogenetic analysis. [ncbi.nlm.nih.gov]

  We confirmed the diagnosis by FISH test. Thus, FISH test can be used in diagnosing rare genetic disorders. Keywords: Chorionic villus sampling, FISH technique, Miller-Dieker How to cite this article: Nair BT, Sanjeev RK, Rai AK. [ssajm.org]

• Developmental Delay

  Results: The developmental delay and similar clinical features in the three patients were most likely due to a common microduplication of 17p13. [jmg.bmj.com]

  Keywords: Miller-Dieker syndrome, classical lissencephaly, developmental delay, infantile spasms, atypical hypsarrythmia, deafness, FISH, 17p13.3, prenatal diagnosis DOI: 10.3233/JPN-2011-0490 Journal: Journal of Pediatric Neurology, vol. 9, no. 3, pp [content.iospress.com]

  At present, the child has gastroesophageal reflux, frequent aspirations, global developmental delay and clusters of seizures suggestive of infantile spasms. [ssajm.org]

  Clinical description Children with MDS present with severe developmental delay, usually have epilepsy, and feeding problems are common. [orpha.net]

• Weakness

  These brain malformations cause severe intellectual disability, developmental delay, seizures, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. [malacards.org]

  Symptoms may include severe intellectual disability, developmental delay, seizures, muscle stiffness, weak muscle tone and feeding difficulties. [diseaseinfosearch.org]

  […] caused by a deletion of genetic material near the end of the short (p) arm of chromosome 17 People with lissencephaly have an abnormally smooth brain with fewer folds and grooves It causes intellectual disability, seizures, abnormal muscle stiffness, weak [dailymail.co.uk]

  For when we are weak, then You are strong. May Jai and Sten feel Your strong arms surrounding them, holding them up when they feel like the world is falling out from under them. [conglomerationofjoy.com]

• Single Transverse Palmar Crease

  transverse palmar crease 0000954 Thick upper lip vermilion Full upper lip Increased volume of upper lip Plump upper lip Prominent upper lip Thick upper lip [ more ] 0000215 Wide nasal bridge Broad nasal bridge Broad nasal root Broadened nasal bridge [rarediseases.info.nih.gov]

• Swelling

  […] to settle thousands of cases involving allegedly defective ASR metal-on-metal hip implants. [4] In 2014 and 2015, Stryker Corporation reportedly followed suit, settling for over $1 billion on more than 4,000 plus personal injury suits alleging pain, swelling [mitchellhamline.edu]

• Strabismus

  Nabi et al. [4] extrapolated that a higher incidence of strabismus in this population likely reflects the higher incidence of strabismus in developmentally delayed children. [eyewiki.aao.org]

  J Pediatr Ophthalmol Strabismus 2000, 37:29–34. PubMed Google Scholar Roach ES, Riela AR, Chugani HT, et al.: Sturge-Weber syndrome: recommendations for surgery. J Child Neurol 1994, 9:190–192. [link.springer.com]

  Facial dysmorphism (proptosis from orbital and midface hypoplasia, external strabismus, mandicular prognathism) is present and extremities are normal. Incidence. The incidence of Crouzon syndrome is 1.6 per 100,000 live births. [radiologykey.com]

• Lower Lid Ectropion

  […] dysostosis 263750 DHODH Autosomal recessive Lower lid ectropion, cupped ears, hearing loss, bilateral absence of fifth fingers, supernumerary nipples Mandibulofacial dysostosis Guion-Almeida type 610536 EFTUD2 Autosomal dominant Microcephaly, developmental [radiologykey.com]

• Reduced Fetal Movement

  History of polyhydramnios, intrauterine growth retardation and reduced fetal movements are associated with MDS. [ijcasereportsandimages.com]

• Psychomotor Retardation

  She underwent surgical closure of patent ductus arteriosus after birth; during development, she displayed psychomotor retardation, language impairment, and short stature. [elsevier.es]

  retardation and infant death. [eyewiki.aao.org]

• Upturned Nares

  However, hypotonia and abnormal facial morphology including prominent forehead, a short nose with upturned nares and protuberant upper lip were developed gradually as he got older. [synapse.koreamed.org]

  All had severe type I lissencephaly with grossly normal cerebellum and a distinctive facial appearance consisting of prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip, thin vermilion border, and small jaw. [ncbi.nlm.nih.gov]

  Miller-Dieker syndrome: A congenital malformation syndrome characterized by lissencephaly ("smooth brain") and a characteristic facial appearance with a prominent forehead with bitemporal hollowing, short nose with upturned nares, thickened upper lip [rxlist.com]

  On examination, child had microcephaly, prominent forehead, a wide nasal bridge, low-set ears, upturned nares, long philtrum (vertical groove on the midline of the upper lip) with thin upper lip, mild micrognathia and delayed dentition [Figure 1]. [ssajm.org]

An infant with the clinical presentation discussed above or a fetus with suspicious findings observed on prenatal ultrasonography warrants a full workup that consists of patient/fetal and family history, a detailed physical exam of the infant, and the appropriate studies discussed below.

Prenatal testing

Obstetric ultrasonography can detect MDS prenatally if performed during late second trimester or later by an experienced operator [1]. Ultrasound scans on fetuses with this disease reveal findings such as a smooth gyral pattern consistent with lissencephaly, ventriculomegaly, other brain abnormalities, intrauterine growth restriction (IUGR), and polyhydramnios [7] [8]. Additionally, congenital anomalies such as omphalocele and heart defects are also identified prenatally [5].

Amniocentesis or chorionic villus sampling (CVS) and subsequent cytogenic analysis can confirm the diagnosis in a fetus suspected to have MDS.

Postnatal imaging

A study reviewing brain computerized tomography (CT) scans and magnetic resonance imaging (MRI) of affected infants demonstrate features such as smooth cerebral hemispheres and a remarkable figure of eight appearance [3]. Frequent findings include a thickened cortex, enlarged cavum septi pellucidi, and diminished or absent corpus callosum [3]. Furthermore, enlarged ventricles and midline calcifications may also be observed [3]. Another study also reported lissencephaly and agenesis of the corpus callosum on CT imaging [9].

Cytogenetic analysis

Patients suspected to have MDS should undergo chromosomal analysis with fluorescence in situ hybridization (FISH) in order to confirm the deletion of the 17p13.3 locus. MDS is associated with multiple genes including LIS1, YWHAE, and CRK in addition to contiguous genes that would contribute to the manifestations of severe forms of the disease [10] [11].

Other

Distinct electroencephalogram (EEG) results associated with MDS include abnormally high amplitude,and rhythmic slow activities [9].

Management and treatment Management of children with MDS is symptomatic. [orpha.net]

Miller-Dieker syndrome is incurable, with no known prenatal treatment options. Postnatal treatment consists largely of antiepileptic therapy for seizure control and supportive care. [researchers.dellmed.utexas.edu]

Treatment is symptomatic and supportive. Source: Genetic and Rare Diseases Information Center (GARD), supported by ORDR-NCATS and NHGRI. [diseaseinfosearch.org]

The treatment of epilepsy: principles and practice. ‏ الصفحة 68 - Committee on Quality Improvement, Subcommittee on Febrile Seizures. Practice parameter: long-term treatment of the child with simple febrile seizures. [books.google.com]

Antiepileptic treatment is usually complex: possible induction of cytochrome P-450 enzymes. In presence of cardiac anomalies, antibiotherapy must be considered. [accessanesthesiology.mhmedical.com]

Treatment and prognosis The overall prognosis is poor with most fetuses not surviving beyond infancy. There may be recurrence rate of ~25% for future pregnancies. [radiopaedia.org]

Prognosis Death often occurs in the first three months of life and most infants with MDS die by two years of age, although there have been reports of individuals living for several years. [checkorphan.org]

MDS is associated with a very poor prognosis. Affected children have severe developmental retardation and are at risk of dying within a few years of life. [symptoma.com]

Prognosis Prognosis varies depending on the particular disorder. FIG 16-22 Abnormal sylvian fissure/insula at 26 weeks. [radiologykey.com]

We wish to emphasize that lissencephaly is etiologically non-specific and represents only one feature in this malformation syndrome. [ncbi.nlm.nih.gov]

Etiology Visible and submicroscopic deletions of 17p13.3, including the LIS1 gene, are found in almost 100% of patients. Management and treatment Management of children with MDS is symptomatic. [orpha.net]

Qualificadores Permitidos Inglês: BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology EH ethnology ET etiology [decs.bvs.br]

Summary Epidemiology MDS is undoubtedly a rare condition with a reported estimate of 1 cases per 100 000 live births, although incidence and prevalence are probably higher. [orpha.net]

In 1991, it was reported in the only published epidemiological study performed in the Dutch population that the prevalence was 11.7 per million live births. [accessanesthesiology.mhmedical.com]

The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.com]

Epidemiology of lissencephaly type 1. Neuroepidemiology 1991.10: 200-4. Guerrini R and Filippi T. Neuronal migration disorders, genetics and epileptogenesis. J Child neurol. 2005;20. 287-299. Dobyns WB, Reiner O, Carrozzo R, Ledbetter DH. [malattierare.toscana.it]

Refrigeration at 2° - 8° C may assist when a delay is not preventable. Do not freeze or place specimens directly on ice. [pathlabs.ufl.edu]

In some cases, it is caused by inheriting a chromosome rearrangement (balanced translocation) from an unaffected parent.[3034] Treatment is based on the symptoms in each person and aims to prevent complications and control seizures.[3035] For more information [rarediseases.org]

Treatment is based on the symptoms in each person and aims to prevent complications and control seizures. [malacards.org]

Prevention Can you prevent Miller-Dieker syndrome? There isn’t a way to prevent spontaneous cases of Miller-Dieker syndrome. [my.clevelandclinic.org]

Prevention How Is Miller-Dieker Lissencephaly Prevented? There is no known way to prevent spontaneous cases of MDS caused by chromosome damage during fetal development. [unitedbrainassociation.org]

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