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Microcephaly-cerebellar hypoplasia-cardiac conduction defect syndrome(MCHCCD)

MedGen UID:
482322
Concept ID:
C3280692
Disease or Syndrome
Synonyms: Microcephaly, cerebellar hypoplasia, and cardiac conduction defect syndrome; ZAKI-GLEESON SYNDROME
SNOMED CT: Zaki Gleeson syndrome (764732004); Microcephalus, cerebellar hypoplasia, cardiac conduction defect syndrome (764732004); Microcephaly, cerebellar hypoplasia, congenital heart conduction defect syndrome (764732004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Monarch Initiative: MONDO:0013735
OMIM®: 614407
Orphanet: ORPHA329332

Definition

The Zaki-Gleeson syndrome is an autosomal recessive neurodevelopmental disorder characterized by profound mental retardation, severe microcephaly, poor growth, cerebellar hypoplasia, and second-degree cardiac conduction defects (Zaki et al., 2011). [from OMIM]

Clinical features

From HPO
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
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).
Long fingers
MedGen UID:
346836
Concept ID:
C1858091
Finding
The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand.
Atrioventricular block
MedGen UID:
13956
Concept ID:
C0004245
Disease or Syndrome
Delayed or lack of conduction of atrial depolarizations through the atrioventricular node to the ventricles.
Bradycardia
MedGen UID:
140901
Concept ID:
C0428977
Finding
A slower than normal heart rate (in adults, slower than 60 beats per minute).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Prominent antihelix
MedGen UID:
335147
Concept ID:
C1845272
Finding
The presence of an abnormally prominent antihelix.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Truncal ataxia
MedGen UID:
96535
Concept ID:
C0427190
Sign or Symptom
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Intellectual disability, profound
MedGen UID:
892508
Concept ID:
C3161330
Mental or Behavioral Dysfunction
Profound mental retardation is defined as an intelligence quotient (IQ) below 20.
Intention tremor
MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Anatomical Abnormality
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Joint contracture of the 5th finger
MedGen UID:
356345
Concept ID:
C1865702
Anatomical Abnormality
Chronic loss of joint motion in the 5th finger due to structural changes in non-bony tissue. The term camptodactyly of the 5th finger is used if the distal and/or proximal interphalangeal joints are affected.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Impaired glucose tolerance
MedGen UID:
852424
Concept ID:
C0151671
Finding
An abnormal resistance to glucose, i.e., a reduction in the ability to maintain glucose levels in the blood stream within normal limits following oral or intravenous administration of glucose.
Glucose intolerance
MedGen UID:
75760
Concept ID:
C0271650
Disease or Syndrome
Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Long eyebrows
MedGen UID:
481761
Concept ID:
C3280131
Finding
Increased length of the hairs of the eyebrows.
Acrocyanosis
MedGen UID:
65138
Concept ID:
C0221347
Finding
Bluish discoloration of the skin of the hands or feet.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMicrocephaly-cerebellar hypoplasia-cardiac conduction defect syndrome
Follow this link to review classifications for Microcephaly-cerebellar hypoplasia-cardiac conduction defect syndrome in Orphanet.

Professional guidelines

PubMed

Wilde AAM, Amin AS, Postema PG
Heart 2022 Mar;108(5):332-338. Epub 2021 May 26 doi: 10.1136/heartjnl-2020-318259. PMID: 34039680Free PMC Article
Statland JM, Fontaine B, Hanna MG, Johnson NE, Kissel JT, Sansone VA, Shieh PB, Tawil RN, Trivedi J, Cannon SC, Griggs RC
Muscle Nerve 2018 Apr;57(4):522-530. Epub 2017 Nov 29 doi: 10.1002/mus.26009. PMID: 29125635Free PMC Article
Wung SF
Crit Care Nurs Clin North Am 2016 Sep;28(3):297-308. Epub 2016 Jun 22 doi: 10.1016/j.cnc.2016.04.003. PMID: 27484658

Recent clinical studies

Etiology

Huizar JF, Kaszala K, Tan A, Koneru J, Mankad P, Kron J, Ellenbogen KA
J Am Coll Cardiol 2023 Mar 28;81(12):1192-1200. doi: 10.1016/j.jacc.2023.01.040. PMID: 36948737Free PMC Article
Ahmed A, Pothineni NVK, Charate R, Garg J, Elbey M, de Asmundis C, LaMeir M, Romeya A, Shivamurthy P, Olshansky B, Russo A, Gopinathannair R, Lakkireddy D
J Am Coll Cardiol 2022 Jun 21;79(24):2450-2462. doi: 10.1016/j.jacc.2022.04.019. PMID: 35710196
Olshansky B, Sullivan RM
Europace 2019 Feb 1;21(2):194-207. doi: 10.1093/europace/euy128. PMID: 29931244
Wilde AAM, Amin AS
JACC Clin Electrophysiol 2018 May;4(5):569-579. Epub 2018 May 2 doi: 10.1016/j.jacep.2018.03.006. PMID: 29798782
Vandael E, Vandenberk B, Vandenberghe J, Willems R, Foulon V
Int J Clin Pharm 2017 Feb;39(1):16-25. Epub 2016 Dec 23 doi: 10.1007/s11096-016-0414-2. PMID: 28012118

Diagnosis

Huizar JF, Kaszala K, Tan A, Koneru J, Mankad P, Kron J, Ellenbogen KA
J Am Coll Cardiol 2023 Mar 28;81(12):1192-1200. doi: 10.1016/j.jacc.2023.01.040. PMID: 36948737Free PMC Article
Ahmed A, Pothineni NVK, Charate R, Garg J, Elbey M, de Asmundis C, LaMeir M, Romeya A, Shivamurthy P, Olshansky B, Russo A, Gopinathannair R, Lakkireddy D
J Am Coll Cardiol 2022 Jun 21;79(24):2450-2462. doi: 10.1016/j.jacc.2022.04.019. PMID: 35710196
Sidhu S, Marine JE
Trends Cardiovasc Med 2020 Jul;30(5):265-272. Epub 2019 Jul 9 doi: 10.1016/j.tcm.2019.07.001. PMID: 31311698
Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, Goldschlager NF, Hamilton RM, Joglar JA, Kim RJ, Lee R, Marine JE, McLeod CJ, Oken KR, Patton KK, Pellegrini CN, Selzman KA, Thompson A, Varosy PD
Circulation 2019 Aug 20;140(8):e382-e482. Epub 2018 Nov 6 doi: 10.1161/CIR.0000000000000628. PMID: 30586772
Wilde AAM, Amin AS
JACC Clin Electrophysiol 2018 May;4(5):569-579. Epub 2018 May 2 doi: 10.1016/j.jacep.2018.03.006. PMID: 29798782

Therapy

Sidhu S, Marine JE
Trends Cardiovasc Med 2020 Jul;30(5):265-272. Epub 2019 Jul 9 doi: 10.1016/j.tcm.2019.07.001. PMID: 31311698
Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, Goldschlager NF, Hamilton RM, Joglar JA, Kim RJ, Lee R, Marine JE, McLeod CJ, Oken KR, Patton KK, Pellegrini CN, Selzman KA, Thompson A, Varosy PD
Circulation 2019 Aug 20;140(8):e382-e482. Epub 2018 Nov 6 doi: 10.1161/CIR.0000000000000628. PMID: 30586772
Olshansky B, Sullivan RM
Europace 2019 Feb 1;21(2):194-207. doi: 10.1093/europace/euy128. PMID: 29931244
Johner N, Namdar M, Shah DC
J Interv Card Electrophysiol 2018 Aug;52(3):293-302. Epub 2018 Aug 20 doi: 10.1007/s10840-018-0413-4. PMID: 30128800
Vandael E, Vandenberk B, Vandenberghe J, Willems R, Foulon V
Int J Clin Pharm 2017 Feb;39(1):16-25. Epub 2016 Dec 23 doi: 10.1007/s11096-016-0414-2. PMID: 28012118

Prognosis

Murariu E, Frigy A
Medicina (Kaunas) 2020 Aug 13;56(8) doi: 10.3390/medicina56080410. PMID: 32823777Free PMC Article
Asatryan B, Medeiros-Domingo A
Europace 2019 Aug 1;21(8):1145-1158. doi: 10.1093/europace/euz109. PMID: 31087102
Johner N, Namdar M, Shah DC
J Interv Card Electrophysiol 2018 Aug;52(3):293-302. Epub 2018 Aug 20 doi: 10.1007/s10840-018-0413-4. PMID: 30128800
Wilde AA, Tan HL
Circ J 2007;71 Suppl A:A12-9. doi: 10.1253/circj.71.a12. PMID: 17587734
Altemose GT, Buxton AE
Annu Rev Med 1999;50:159-77. doi: 10.1146/annurev.med.50.1.159. PMID: 10073270

Clinical prediction guides

Murariu E, Frigy A
Medicina (Kaunas) 2020 Aug 13;56(8) doi: 10.3390/medicina56080410. PMID: 32823777Free PMC Article
Sidhu S, Marine JE
Trends Cardiovasc Med 2020 Jul;30(5):265-272. Epub 2019 Jul 9 doi: 10.1016/j.tcm.2019.07.001. PMID: 31311698
Gourraud JB, Barc J, Thollet A, Le Marec H, Probst V
Arch Cardiovasc Dis 2017 Mar;110(3):188-195. Epub 2017 Jan 27 doi: 10.1016/j.acvd.2016.09.009. PMID: 28139454
Vandael E, Vandenberk B, Vandenberghe J, Willems R, Foulon V
Int J Clin Pharm 2017 Feb;39(1):16-25. Epub 2016 Dec 23 doi: 10.1007/s11096-016-0414-2. PMID: 28012118
Brugada R, Campuzano O, Sarquella-Brugada G, Brugada J, Brugada P
Methodist Debakey Cardiovasc J 2014 Jan-Mar;10(1):25-8. doi: 10.14797/mdcj-10-1-25. PMID: 24932359Free PMC Article

Recent systematic reviews

Majeed H, Khan U, Khan AM, Khalid SN, Farook S, Gangu K, Sagheer S, Sheikh AB
Curr Probl Cardiol 2023 Jun;48(6):101663. Epub 2023 Feb 24 doi: 10.1016/j.cpcardiol.2023.101663. PMID: 36842470
Chivers S, Ovadia C, Regan W, Zidere V, Vigneswaran T, Sharland G, Rosenthal E, Seed PT, Simpson JM, Williamson C
Heart Rhythm 2023 Apr;20(4):596-606. Epub 2022 Dec 22 doi: 10.1016/j.hrthm.2022.12.026. PMID: 36566891
Galić E, Bešlić P, Kilić P, Planinić Z, Pašalić A, Galić I, Ćubela VV, Pekić P
Acta Clin Croat 2021 Dec;60(4):739-748. doi: 10.20471/acc.2021.60.04.22. PMID: 35734489Free PMC Article
Beach SR, Gross AF, Hartney KE, Taylor JB, Rundell JR
Gen Hosp Psychiatry 2020 Nov-Dec;67:42-50. Epub 2020 Aug 22 doi: 10.1016/j.genhosppsych.2020.08.008. PMID: 32979582
Vandael E, Vandenberk B, Vandenberghe J, Willems R, Foulon V
Int J Clin Pharm 2017 Feb;39(1):16-25. Epub 2016 Dec 23 doi: 10.1007/s11096-016-0414-2. PMID: 28012118

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