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 Table of Contents  
Year : 2014  |  Volume : 1  |  Issue : 4  |  Page : 210-212

Miller-Dieker syndrome: Confirmation by fluorescence in situ hybridization technique

Department of Paediatrics, Army College of Medical Sciences, New Delhi, India

Date of Submission01-Jun-2014
Date of Acceptance18-Aug-2014
Date of Web Publication14-Nov-2014

Correspondence Address:
Bindu Thankamany Nair
Department of Pediatrics, Army College of Medical Sciences, Delhi Cantonment, New Delhi - 110 010
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2384-5147.144745

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A male child presented at 2 years of age with intractable infantile spasms. He had various dysmorphic features, global developmental delay and inability to feed. The electroencephalogram and MRI was suggestive of lissencephaly. 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. Miller-Dieker syndrome: Confirmation by fluorescence in situ hybridization technique. Sub-Saharan Afr J Med 2014;1:210-2

How to cite this URL:
Nair BT, Sanjeev RK, Rai AK. Miller-Dieker syndrome: Confirmation by fluorescence in situ hybridization technique. Sub-Saharan Afr J Med [serial online] 2014 [cited 2022 Aug 19];1:210-2. Available from: https://www.ssajm.org/text.asp?2014/1/4/210/144745

  Introduction Top

Miller-Dieker syndrome (MDS) consists of classical lissencephaly, characteristic facial abnormalities and sometimes other birth defects. [1] The facial changes consist of prominent forehead, bitemporal hollowing, short nose with upturned nares, flat midface, protuberant upper lip with thin vermillion border and small jaw. It is associated with visible or submicroscopic rearrangements within chromosome band 17p13.3 in almost all patients. [2]

We report a case where the clinical diagnosis was confirmed by FISH technique and the same technique can be done to confirm an affected sibling antenatally either by amniocentesis or chorionic villus sampling.

  Case report Top

A 2-year-old male child, first product of nonconsanguineous marriage, presented with recurrent episodes of abnormal body movements since 4 months of age. Child was apparently normal till 4 months of age, when he had first episode of abnormal body movements characterized by tonic flexion of upper limb and extension of lower limb with up rolling of eyeballs. Each episode lasted just for few min. Initially 10-15 episodes occurred in 1-day. The baby was born at 39 weeks gestation following an uncomplicated pregnancy and delivery, with a birth weight of 2600 g. Child achieved social smile and partial neck holding initially but after onset of seizures, there was no further achievement of any milestones. Family history was not suggestive of any similar illness.

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]. Child's present weight is 9.3 kg (76% of 50 th centile), OFC-45.5 cm (less than 3 rd centile). Vital parameters are normal for age. Child has global developmental delay, severe mental retardation and only babbles. Has generalized hypotonia, power is Grade1/5 in all muscle groups and deep tendon reflexes are poorly elicitable.
Figure 1: Child showing dysmorphic features

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Fundus evaluation was normal. Ultrasonography of abdomen and echocardiography was normal. Cranial magnetic resonance imaging showed complete absence of cerebral sulci with a smooth brain surface consistent with classical (Type I) lissencephaly [Figure 2]. Electroencephalography indicated frequent multifocal independent spikes, sharp waves, and early features of evolving hypsarrhythmia. FISH test by hybridized MDS probe - L1S1 (PAFAH1B1) localised to17p13.3 showed variation in signal size of chromosome 17p consistent with Miller-Dieker syndrome.
Figure 2: Magnetic resonance imaging showing lissencephaly

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Child has been started on multiple antiepileptic drugs (AEDs) with partial resolution of the seizures. He is on regular follow-up with continuation of AEDs. At present, the child has gastroesophageal reflux, frequent aspirations, global developmental delay and clusters of seizures suggestive of infantile spasms.

  Discussion Top

Miller in (1963) and later Dieker in (1969) described a specific pattern of malformations, one feature of which was lissencephaly. [3],[4] They emphasized that this should be called lissencephaly syndrome. Jones expanded the clinical phenotype and introduced the term Miller-Dieker syndrome to distinguish this disorder from other conditions associated with lissencephaly. [3],[4],[5] There may be associated cardiac and renal defects, sacral dimples, joint contractures, and abnormal genitalia in males. [6]

Miller-Dieker syndrome is undoubtedly a rare condition. The only published (1991) data on the prevalence of classical lissencephaly (lissencephaly Type I) comes from a Dutch study, reporting 11.7 per million live births. About 25-30% of patients with classical lissencephaly have MDS. However with improved seizure management, and use of gastrostomies to treat feeding problems, children with MDS now often have a longer survival.

Classical lissencephaly can usually only be recognised on imaging after 28 weeks of pregnancy, as cerebral gyri are not fully developed prior to this gestation. [7],[8],[9] Miller-Dieker syndrome can be diagnosed antenatally by amniocentesis or chorionic villus sampling, when parents are found to have a balanced translocation. The risk of recurrence is extremely low in cases of de novo deletion. Approximately 80% of patients have a de novo deletion; the remainder have an inherited deletion from a parental rearrangement. [10]

Molecular cytogenetic technology should be used in cases of suspected Miller-Dieker syndrome when high-resolution cytogenetic analysis fails to detect deletion 17p13.3. Positive findings should be followed-up with parental studies. FISH studies are now strongly recommended to detect cryptic translocations involving 17p13.3 that are not demonstrated by conventional chromosome studies.

Often parents of children with a developmental disability want to know more about their child's conditions before choosing to have another child. These concerns can be addressed by analysis of the parents' and child's DNA. In cases where the child's developmental disability is not understood, the cause of it can potentially be determined using FISH and cytogenetic techniques. Examples of diseases that are diagnosed using FISH include  Prader-Willi syndrome More Details, Angelman syndrome, 22q13 deletion syndrome, chronic myelogenous leukemia, acute lymphoblastic leukemia, Cri-du-chat, Velocardiofacial syndrome, and Down syndrome. [10]

  References Top

Dobyns WB, Curry CJ, Hoyme HE, Turlington L, Ledbetter DH. Clinical and molecular diagnosis of Miller-Dieker syndrome. Am J Hum Genet 1991;48:584-94.  Back to cited text no. 1
Dobyns WB, Reiner O, Carrozzo R, Ledbetter DH. Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 1993;270:2838-42.  Back to cited text no. 2
Mckusick VJ. Mendelian Inheritance in Man: Catalogs of Autosomal Dominant, Autosomal Recessive, and X-Linked Phenotypes. N Engl J Med 1993;329:585-6.  Back to cited text no. 3
Buyse ML. Birth Defects Encyclopedia. Massachussetts: Blackwell Scientific Publications; 1990. p. 1074-5.  Back to cited text no. 4
Jones KL. Smith's Recognizable Patterns of Human Malformation. 4 th ed. Philadelphia: W.B. Saunders Company; 1988. p. 161-2.  Back to cited text no. 5
Guerrini R, Filippi T. Neuronal migration disorders, genetics, and epileptogenesis. J Child Neurol 2005;20:287-99.  Back to cited text no. 6
Greenberg F, Stratton RF, Lockhart LH, Elder FF, Dobyns WB, Ledbetter DH. Familial Miller-Dieker syndrome associated with pericentric inversion of chromosome 17. Am J Med Genet 1986;23:853-9.  Back to cited text no. 7
Gupte GL, Kher AS, Joshi SM, Bharucha BA, Kanade SP. Lissencephaly. Indian Pediatr 1995;32:593-6.  Back to cited text no. 8
Pilz DT, Quarrell OW. Syndromes with lissencephaly. J Med Genet 1996;33:319-23.  Back to cited text no. 9
Kuwano A, Ledbetter SA, Dobyns WB, Emanuel BS, Ledbetter DH. Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization. Am J Hum Genet 1991;49:707-14.  Back to cited text no. 10


  [Figure 1], [Figure 2]


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