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Miller Dieker Syndrome

Miller-Dieker Syndrome

Miller-Dieker syndrome is a rare disorder with contiguous gene deletion that is characterized by lissencephaly, distinct facial and other congenital anomalies. It is associated with seizures, mental delay, and early death.


Presentation

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].

Recurrent Urinary Tract Infection
  • Recurrent urinary tract infections were diagnosed during routine out-patient department follow-up. Urodynamic study disclosed a neurogenic bladder.[ncbi.nlm.nih.gov]
Dolichocephaly
  • Retrospective analysis showed a prenatal scan reporting dolichocephaly.[ncbi.nlm.nih.gov]
Axillary Freckling
Unilateral Ptosis
  • The proband was determined at birth owing to the presence of multiple congenital anomalies, including low birth weight, microcephaly, agenesis of the corpus callosum, lissencephaly, cerebral atrophy, unilateral ptosis, polydactyly, and omphalocele.[ncbi.nlm.nih.gov]
Reduced Fetal Movement
  • History of polyhydramnios, intrauterine growth retardation and reduced fetal movements are associated with MDS.[ijcasereportsandimages.com]
Psychomotor Retardation
Upturned Nares
  • 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]
  • 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[symptoma.com]
  • 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[medicinenet.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]

Workup

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].

Rhythmic Slowing
  • Other Distinct electroencephalogram (EEG) results associated with MDS include abnormally high amplitude,and rhythmic slow activities.[symptoma.com]

Treatment

  • Management and treatment Management of children with MDS is symptomatic.[orpha.net]
  • Direct in style but comprehensive in content, with ample tables and summaries, the Handbook of Epilepsy Treatment covers: Treatment of the different forms and causes of epilepsy Treatment in the different commonly encountered clinical situations Treatment[books.google.com]
  • Treatment is symptomatic and supportive. Source: Genetic and Rare Diseases Information Center (GARD), supported by ORDR-NCATS and NHGRI.[diseaseinfosearch.org]
  • Please consult your own licensed physician regarding diagnosis and treatment of any medical condition! Please see also our disclaimer . This site complies with the HONcode standard for health information: verify here . Database updated 2019-02-19.[diseasesdatabase.com]

Prognosis

  • 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]
  • 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]
  • An accurate diagnosis of MDS is important not only because it can provide a prognosis for the affected child, but because it can give parents an estimate of their risk for having another child with MDS.[checkorphan.org]
  • Prognosis Most babies with Miller Dieker Syndrome die in the first three months of life and most infants are dead from complications of seizures, aspiration pneumonia etc. within two years of age.[nethealthbook.com]
  • Prognosis in this concurrent phenotype is poor with our patient suffering from several malformations seen in both conditions and expiring in the neonatal period.[thieme-connect.com]

Etiology

  • 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]
  • Karyotype assessment is important to consider in all epilepsies where the etiology is uncertain as dysmorphic features may be subtle or not apparent. Karyotype examination should be extended to 50-100 mitoses to exclude mosaicism.[epilepsydiagnosis.org]
  • Our subsequent identification of apparently non-overlapping deletions of LIS1 in patients MDS-019 and MDS-021 had suggested otherwise,and instead implicated LIS1 in the etiology of the complete MDS phenotype ( 6 ).[doi.org]

Epidemiology

  • 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]
  • Epidemiology [ edit ] Miller-Dieker occurs in less than one in 100000 people and can occur in all races. [ citation needed ] History [ edit ] MDS was named for the two physicians, James Q. Miller [7] and H.[en.wikipedia.org]
  • Epidemiology Miller-Dieker occurs in less than one in 100000 people and can occur in all races. History MDS was named for the two physicians, J. Miller and H. Dieker, who independently described the condition in the 1960s.[ipfs.io]
  • 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]
  • June 2003;3(3):178-184. de Rijk-van Andel JF, Arts WF, Hofman A, Staal A, Niermeijer MF. “ Epidemiology of lissencephaly type I .” Neuroepidemiology. 1991;10:200-4.[eyewiki.aao.org]
Sex distribution
Age distribution

Prevention

  • Treatment is based on the symptoms in each person and aims to prevent complications and control seizures.[malacards.org]
  • Prevention - Miller-Dieker syndrome Not supplied. Diagnosis - Miller-Dieker syndrome MDS is not the only disorder associated with lissencephaly.[checkorphan.org]
  • Lack of relevant family history can also prevent suspicion in many cases.[ipfs.io]
  • A little boy born with a rare brain disease that prevented him from being able to cry or feed properly, has died at just eight weeks old.[dailymail.co.uk]
  • Anesthesiologists should prevent perioperative pulmonary dysfunction and clear secretions in the airways. MDS may also be associated with congenital heart diseases, genitourinary abnormalities, and sacral dimples [ 1, 10 ].[jaclinicalreports.springeropen.com]

References

Article

  1. Fong KW, Ghai S, Toi A, et al. Prenatal ultrasound findings of lissencephaly associated with Miller-Dieker syndrome and comparison with pre- and postnatal magnetic resonance imaging. Ultrasound Obstet Gynecol. 2004;24(7):716-23.
  2. Atwal PS, Macmurdo C. A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2 Deletion Syndrome. J Pediatr Genet. 2015;4(4):201-203.
  3. Dobyns WB, Curry CJR, Hoyme HE, Turlington L, Ledbetter DH. Clinical and molecular diagnosis of Miller–Dieker syndrome. Am J Hum Genet. 1991;48(3): 584–594.
  4. Dobyns WB, Stratton RF, Greenberg F. Syndromes with lissencephaly 1: Miller–Dieker and Norman–Robert syndromes and isolated lissencephaly. Am J Med Genet. 1984;18(3):509–526.
  5. Chitayat D, Toi A, Babul R, et al. Omphalocele in Miller–Dieker syndrome: expanding the phenotype. Am J Med Genet. 1997;69(3): 293–298.
  6. Cardoso C, Leventer RJ, Ward HL, et al. Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. Am J Hum Genet. 2003;72(4):918–30.
  7. Saltzman DH, Krauss CM, Goldman JM, Benaceraff BR. Prenatal diagnosis of lissencephaly. Prenat Diagn. 1991;11(3):139–143.
  8. McGahan JP, Grix A, Gerscovich EO. Prenatal diagnosis of lissencephaly—Miller–Dieker syndrome. J Clin ultrasound. 1994;22(9):560–563.
  9. Sharief N, Craze J, Summers D, Butler L, Wood CB. Miller-Dieker syndrome with ring chromosome 17. Arch Dis Child. 1991;66(6):710-2.
  10. Ghai S, Fong KW, Toi A, et al. Prenatal US and MR imaging findings of lissencephaly: review of fetal cerebral sulcal development. Radiographics. 2006;26(2):389-405.
  11. Toyo-oka K, Shionoya A, Gambello MJ, et al. 14–3-3ε is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet. 2003;34(3):274-85.

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Last updated: 2019-07-11 20:52