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Periventricular nodular heterotopia 9(PVNH9)

MedGen UID:
1718470
Concept ID:
C5394503
Disease or Syndrome
Synonyms: PERIVENTRICULAR NODULAR HETEROTOPIA 9; PVNH9
 
Gene (location): MAP1B (5q13.2)
 
Monarch Initiative: MONDO:0030061
OMIM®: 618918

Definition

Periventricular nodular heterotopia-9 (PVNH9) is an autosomal dominant neurologic disorder characterized as a malformation of cortical development. Anterior predominant PVNH, thin corpus callosum, and decreased white matter volume are found on brain imaging, but the clinical effects are variable. Most patients have impaired intellectual development and cognitive defects associated with low IQ (range 50 to 80), learning disabilities, and behavior abnormalities. Some patients develop seizures that tend to have a focal origin. However, some mutation carriers may be less severely affected with borderline or even normal IQ, suggesting incomplete penetrance of the phenotype (summary by Heinzen et al., 2018, Walters et al., 2018). For a discussion of genetic heterogeneity of periventricular nodular heterotopia, see 300049. [from OMIM]

Clinical features

From HPO
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Squared superior portion of helix
MedGen UID:
868279
Concept ID:
C4022671
Finding
Flattening instead of curving or rounded superior helix, allowing the superior helix to run more horizontally than usual.
Polymicrogyria
MedGen UID:
78605
Concept ID:
C0266464
Congenital Abnormality
Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).
Gray matter heterotopia
MedGen UID:
452349
Concept ID:
C0266491
Finding
Heterotopia or neuronal heterotopia are macroscopic clusters of misplaced neurons (gray matter), most often situated along the ventricular walls or within the subcortical white matter.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Dyslexia
MedGen UID:
96906
Concept ID:
C0476254
Mental or Behavioral Dysfunction
A learning disorder characterized primarily by difficulties in learning to read and spell. Dyslectic children also exhibit a tendency to read words from right to left and to confuse letters such as b and d whose orientation is important for their identification. Children with dyslexia appear to be impaired in phonemic skills (the ability to associate visual symbols with the sounds they represent).
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Compulsive behaviors
MedGen UID:
109373
Concept ID:
C0600104
Mental or Behavioral Dysfunction
Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Broad-based gait
MedGen UID:
167799
Concept ID:
C0856863
Finding
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Dyscalculia
MedGen UID:
452779
Concept ID:
C0869474
Mental or Behavioral Dysfunction
A specific learning disability involving mathematics and arithmetic.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Periventricular nodular heterotopia
MedGen UID:
358387
Concept ID:
C1868720
Disease or Syndrome
Nodules of heterotopia along the ventricular walls. There can be a single nodule or a large number of nodules, they can exist on either or both sides of the brain at any point along the higher ventricle margins, they can be small or large, single or multiple.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Mild global developmental delay
MedGen UID:
861405
Concept ID:
C4012968
Finding
A mild delay in the achievement of motor or mental milestones in the domains of development of a child.
Interictal epileptiform activity
MedGen UID:
869073
Concept ID:
C4023491
Finding
Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure.
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Vertical bony ridge positioned in the midline of the forehead.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Gingival overgrowth
MedGen UID:
87712
Concept ID:
C0376480
Finding
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Hypoplastic philtrum
MedGen UID:
341641
Concept ID:
C1856886
Finding
Underdevelopment of the philtrum.
Everted upper lip vermilion
MedGen UID:
869272
Concept ID:
C4023698
Finding
Inner aspect of the upper lip vermilion (normally apposing the teeth) visible in a frontal view, i.e., the presence of an everted upper lip.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.
Prominent fingertip pads
MedGen UID:
322758
Concept ID:
C1835807
Finding
A soft tissue prominence of the ventral aspects of the fingertips. The term "persistent fetal fingertip pads" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist.

Recent clinical studies

Etiology

Lee KS, Seunarine KK, Barnes N, Tahir MZ, Varadkar SM, Tisdall MM
J Neurosurg Pediatr 2023 Aug 1;32(2):214-222. Epub 2023 May 19 doi: 10.3171/2023.4.PEDS2318. PMID: 37209074
Paliotti K, Dassi C, Berrahmoune S, Bejaran ML, Davila CEV, Martinez AB, Estupiñà MCF, Mancardi MM, Riva A, Giacomini T, Severino M, Romaniello R, Dubeau F, Srour M, Myers KA
J Neurol 2023 Aug;270(8):3934-3945. Epub 2023 Apr 29 doi: 10.1007/s00415-023-11724-z. PMID: 37119372
Lu YT, Hsu CY, Liu YT, Chan CK, Chuang YC, Lin CH, Chang KP, Ho CJ, Ng CC, Lim KS, Tsai MH
Biomed J 2022 Jun;45(3):542-548. Epub 2021 May 20 doi: 10.1016/j.bj.2021.05.003. PMID: 35660364Free PMC Article
Cellini E, Vetro A, Conti V, Marini C, Doccini V, Clementella C, Parrini E, Giglio S, Della Monica M, Fichera M, Musumeci SA, Guerrini R
Eur J Hum Genet 2019 Jun;27(6):909-918. Epub 2019 Jan 25 doi: 10.1038/s41431-019-0335-3. PMID: 30683929Free PMC Article
Deloison B, Sonigo P, Millischer-Bellaiche AE, Quibel T, Cavallin M, Benoist G, Quelin C, Jouk PS, Lev D, Alison M, Baumann C, Beldjord C, Razavi F, Bessières B, Boddaert N, Ville Y, Salomon LJ, Bahi-Buisson N
Eur J Med Genet 2018 Dec;61(12):773-782. Epub 2018 Nov 1 doi: 10.1016/j.ejmg.2018.10.015. PMID: 30391507

Diagnosis

Liu W, Hu X, An D, Zhou D, Gong Q
Sci Rep 2019 Dec 5;9(1):18473. doi: 10.1038/s41598-019-55002-3. PMID: 31804610Free PMC Article
Di Giacomo R, Uribe-San-Martin R, Mai R, Francione S, Nobili L, Sartori I, Gozzo F, Pelliccia V, Onofrj M, Lo Russo G, de Curtis M, Tassi L
Seizure 2019 Nov;72:54-60. Epub 2019 Oct 5 doi: 10.1016/j.seizure.2019.10.001. PMID: 31606703
Cellini E, Vetro A, Conti V, Marini C, Doccini V, Clementella C, Parrini E, Giglio S, Della Monica M, Fichera M, Musumeci SA, Guerrini R
Eur J Hum Genet 2019 Jun;27(6):909-918. Epub 2019 Jan 25 doi: 10.1038/s41431-019-0335-3. PMID: 30683929Free PMC Article
Deloison B, Sonigo P, Millischer-Bellaiche AE, Quibel T, Cavallin M, Benoist G, Quelin C, Jouk PS, Lev D, Alison M, Baumann C, Beldjord C, Razavi F, Bessières B, Boddaert N, Ville Y, Salomon LJ, Bahi-Buisson N
Eur J Med Genet 2018 Dec;61(12):773-782. Epub 2018 Nov 1 doi: 10.1016/j.ejmg.2018.10.015. PMID: 30391507
Lee CH, Wai YY, Wu T
Chang Gung Med J 2011 Nov-Dec;34(6):628-35. PMID: 22196066

Therapy

Cellini E, Vetro A, Conti V, Marini C, Doccini V, Clementella C, Parrini E, Giglio S, Della Monica M, Fichera M, Musumeci SA, Guerrini R
Eur J Hum Genet 2019 Jun;27(6):909-918. Epub 2019 Jan 25 doi: 10.1038/s41431-019-0335-3. PMID: 30683929Free PMC Article
Myers KA, Mandelstam SA, Ramantani G, Rushing EJ, de Vries BB, Koolen DA, Scheffer IE
Epilepsia 2017 Jun;58(6):1085-1094. Epub 2017 Apr 25 doi: 10.1111/epi.13746. PMID: 28440867

Prognosis

McCormack RM, Chandran AS, Lhatoo SD, Pati S, Li Z, Harris K, Lacuey N, Kalamangalam G, Thompson S, Tandon N
Ann Neurol 2024 Dec;96(6):1174-1184. Epub 2024 Sep 19 doi: 10.1002/ana.27059. PMID: 39297387
Paliotti K, Dassi C, Berrahmoune S, Bejaran ML, Davila CEV, Martinez AB, Estupiñà MCF, Mancardi MM, Riva A, Giacomini T, Severino M, Romaniello R, Dubeau F, Srour M, Myers KA
J Neurol 2023 Aug;270(8):3934-3945. Epub 2023 Apr 29 doi: 10.1007/s00415-023-11724-z. PMID: 37119372
Lotan E, Tomer O, Tavor I, Blatt I, Goldberg-Stern H, Hoffmann C, Tsarfaty G, Tanne D, Assaf Y
Neuroradiology 2021 Feb;63(2):225-234. Epub 2020 Sep 25 doi: 10.1007/s00234-020-02561-2. PMID: 32975591
Liu W, An D, Tong X, Niu R, Gong Q, Zhou D
Epilepsy Res 2017 Oct;136:137-142. Epub 2017 Aug 23 doi: 10.1016/j.eplepsyres.2017.08.007. PMID: 28850831
Li LM, Dubeau F, Andermann F, Fish DR, Watson C, Cascino GD, Berkovic SF, Moran N, Duncan JS, Olivier A, Leblanc R, Harkness W
Ann Neurol 1997 May;41(5):662-8. doi: 10.1002/ana.410410516. PMID: 9153529

Clinical prediction guides

McCormack RM, Chandran AS, Lhatoo SD, Pati S, Li Z, Harris K, Lacuey N, Kalamangalam G, Thompson S, Tandon N
Ann Neurol 2024 Dec;96(6):1174-1184. Epub 2024 Sep 19 doi: 10.1002/ana.27059. PMID: 39297387
Paliotti K, Dassi C, Berrahmoune S, Bejaran ML, Davila CEV, Martinez AB, Estupiñà MCF, Mancardi MM, Riva A, Giacomini T, Severino M, Romaniello R, Dubeau F, Srour M, Myers KA
J Neurol 2023 Aug;270(8):3934-3945. Epub 2023 Apr 29 doi: 10.1007/s00415-023-11724-z. PMID: 37119372
Lu YT, Hsu CY, Liu YT, Chan CK, Chuang YC, Lin CH, Chang KP, Ho CJ, Ng CC, Lim KS, Tsai MH
Biomed J 2022 Jun;45(3):542-548. Epub 2021 May 20 doi: 10.1016/j.bj.2021.05.003. PMID: 35660364Free PMC Article
Lotan E, Tomer O, Tavor I, Blatt I, Goldberg-Stern H, Hoffmann C, Tsarfaty G, Tanne D, Assaf Y
Neuroradiology 2021 Feb;63(2):225-234. Epub 2020 Sep 25 doi: 10.1007/s00234-020-02561-2. PMID: 32975591
Deloison B, Sonigo P, Millischer-Bellaiche AE, Quibel T, Cavallin M, Benoist G, Quelin C, Jouk PS, Lev D, Alison M, Baumann C, Beldjord C, Razavi F, Bessières B, Boddaert N, Ville Y, Salomon LJ, Bahi-Buisson N
Eur J Med Genet 2018 Dec;61(12):773-782. Epub 2018 Nov 1 doi: 10.1016/j.ejmg.2018.10.015. PMID: 30391507

Recent systematic reviews

Mutti C, Riccò M, Bartolini Y, Bernabè G, Trippi I, Melpignano A, Ciliento R, Zinno L, Florindo I, Sasso E, Odone A, Parrino L, Vaudano AE
Epilepsia 2021 Feb;62(2):383-396. Epub 2020 Dec 16 doi: 10.1111/epi.16787. PMID: 33325054

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