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Mitochondrial complex IV deficiency, nuclear type 23(MC4DN23)

MedGen UID:
1840958
Concept ID:
C5830322
Disease or Syndrome
Synonym: MC4DN23
 
Gene (location): COX11 (17q22)
 
Monarch Initiative: MONDO:0859520
OMIM®: 620275

Definition

Mitochondrial complex IV deficiency nuclear type 23 (MC4DN23) is an autosomal recessive disorder characterized by infantile-onset encephalopathy (Rius et al., 2022). For a discussion of genetic heterogeneity of mitochondrial complex IV (cytochrome c oxidase) deficiency, see 220110. [from OMIM]

Clinical features

From HPO
Knee contracture
MedGen UID:
332406
Concept ID:
C1837263
Anatomical Abnormality
Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the knee joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Clonic seizure
MedGen UID:
66708
Concept ID:
C0234535
Disease or Syndrome
A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive.
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.
Increased CSF lactate
MedGen UID:
257904
Concept ID:
C1167918
Finding
Increased concentration of lactate in the cerebrospinal fluid.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Elevated brain lactate level by MRS
MedGen UID:
868368
Concept ID:
C4022762
Finding
An increase in the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS).
Brain atrophy
MedGen UID:
1643639
Concept ID:
C4551584
Disease or Syndrome
Partial or complete wasting (loss) of brain tissue that was once present.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
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.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Percussion myotonia
MedGen UID:
148293
Concept ID:
C0751359
Finding
A localized myotonic contraction in a muscle in reaction to percussion (tapping with the examiner's finger, a rubber percussion hammer, or a similar object).
Elbow contracture
MedGen UID:
331445
Concept ID:
C1833142
Anatomical Abnormality
A limitation in the passive range of motion of the elbow resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin.
Nemaline bodies
MedGen UID:
814369
Concept ID:
C3808039
Finding
Nemaline rods are abnormal bodies that can occur in skeletal muscle fibers. The rods can be observed on histological analysis of muscle biopsy tissue or upon electron microscopy, where they appear either as extensions of sarcomeric Z-lines, in random array without obvious attachment to Z-lines (often in areas devoid of sarcomeres) or in large clusters localized at the sarcolemma or intermyofibrillar spaces.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Hypoventilation
MedGen UID:
469022
Concept ID:
C3203358
Pathologic Function
A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide).
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).
Fetal distress
MedGen UID:
5164
Concept ID:
C0015930
Pathologic Function
An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Recent clinical studies

Etiology

Mili S, Piñol-Roma S
Mol Cell Biol 2003 Jul;23(14):4972-82. doi: 10.1128/MCB.23.14.4972-4982.2003. PMID: 12832482Free PMC Article

Diagnosis

Piro E, Serra G, Antona V, Giuffrè M, Giorgio E, Sirchia F, Schierz IAM, Brusco A, Corsello G
Ital J Pediatr 2020 Sep 24;46(1):140. doi: 10.1186/s13052-020-00903-7. PMID: 32972427Free PMC Article
Abdulhag UN, Soiferman D, Schueler-Furman O, Miller C, Shaag A, Elpeleg O, Edvardson S, Saada A
Eur J Hum Genet 2015 Feb;23(2):159-64. Epub 2014 Apr 30 doi: 10.1038/ejhg.2014.85. PMID: 24781756Free PMC Article

Prognosis

Abdulhag UN, Soiferman D, Schueler-Furman O, Miller C, Shaag A, Elpeleg O, Edvardson S, Saada A
Eur J Hum Genet 2015 Feb;23(2):159-64. Epub 2014 Apr 30 doi: 10.1038/ejhg.2014.85. PMID: 24781756Free PMC Article
Mili S, Piñol-Roma S
Mol Cell Biol 2003 Jul;23(14):4972-82. doi: 10.1128/MCB.23.14.4972-4982.2003. PMID: 12832482Free PMC Article

Clinical prediction guides

Piro E, Serra G, Antona V, Giuffrè M, Giorgio E, Sirchia F, Schierz IAM, Brusco A, Corsello G
Ital J Pediatr 2020 Sep 24;46(1):140. doi: 10.1186/s13052-020-00903-7. PMID: 32972427Free PMC Article
Abdulhag UN, Soiferman D, Schueler-Furman O, Miller C, Shaag A, Elpeleg O, Edvardson S, Saada A
Eur J Hum Genet 2015 Feb;23(2):159-64. Epub 2014 Apr 30 doi: 10.1038/ejhg.2014.85. PMID: 24781756Free PMC Article
Mili S, Piñol-Roma S
Mol Cell Biol 2003 Jul;23(14):4972-82. doi: 10.1128/MCB.23.14.4972-4982.2003. PMID: 12832482Free PMC Article

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