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Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay(CCDDRD)

MedGen UID:
1848439
Concept ID:
C5882675
Disease or Syndrome
Synonym: CCDDRD
 
Gene (location): NEUROG1 (5q31.1)
 
Monarch Initiative: MONDO:0957563
OMIM®: 620469

Definition

Congenital cranial dysinnervation disorder with absent corneal reflex and developmental delay (CCDDRD) is an autosomal recessive disorder characterized by abnormal development of the proximal cranial sensory ganglia and nerves, mainly CN V (trigeminal nerve) and CN VIII (vestibulocochlear nerve). Affected individuals present at birth or in early infancy with corneal opacities due to absent blinking. Most patients also have sensorineural deafness associated with hypoplastic or malformed cochlea and hypoplasia or agenesis of CN VIII. Developmental delay with poor speech and autistic behavior are also present. Additional features may include expressionless face, feeding or chewing difficulties due to oromotor dysfunction, and dysmorphic facial features (Dupont et al., 2021; Sheth et al., 2023). [from OMIM]

Clinical features

From HPO
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.
Hypoplasia of the cochlea
MedGen UID:
436824
Concept ID:
C2676974
Finding
Developmental hypoplasia of the cochlea.
Profound sensorineural hearing impairment
MedGen UID:
868926
Concept ID:
C4023338
Disease or Syndrome
Complete loss of hearing related to a sensorineural defect.
Absent internal auditory canal
MedGen UID:
868970
Concept ID:
C4023384
Anatomical Abnormality
Aplasia of the internal auditory canal.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
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.
Insomnia
MedGen UID:
214589
Concept ID:
C0917801
Sign or Symptom
Persistent difficulty initiating or maintaining sleep.
Sensory axonal neuropathy
MedGen UID:
334116
Concept ID:
C1842587
Finding
An axonal neuropathy of peripheral sensory nerves.
Hyperintensity of cerebral white matter on MRI
MedGen UID:
811125
Concept ID:
C2938912
Pathologic Function
A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter.
Profound global developmental delay
MedGen UID:
766364
Concept ID:
C3553450
Disease or Syndrome
A profound delay in the achievement of motor or mental milestones in the domains of development of a child.
Hyperkinetic movements
MedGen UID:
854367
Concept ID:
C3887506
Disease or Syndrome
Motor hyperactivity with excessive movement of muscles of the body as a whole.
Myoclonic seizure
MedGen UID:
1385980
Concept ID:
C4317123
Sign or Symptom
A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
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.
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
Impaired mastication
MedGen UID:
66779
Concept ID:
C0239043
Finding
An abnormal reduction in the ability to masticate (chew), i.e., in the ability to crush and ground food in preparation for swallowing.
Mask-like facies
MedGen UID:
140860
Concept ID:
C0424448
Finding
A lack of facial expression often with staring eyes and a slightly open mouth.
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
Narrow palate
MedGen UID:
278045
Concept ID:
C1398312
Finding
Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective).
Long palpebral fissure
MedGen UID:
340300
Concept ID:
C1849340
Finding
Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures.
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.
Absent corneal reflex
MedGen UID:
78835
Concept ID:
C0278211
Finding
Absence of the corneal blinking reflex, which normally induces involuntary blinking of the eyelids following contact of the cornea. The corneal blink reflex is caused by a loop between the trigeminal sensory nerves and the facial motor (VII) nerve innervation of the orbicularis oculi muscles.

Recent clinical studies

Etiology

Dupont J, Vieira JP, Tavares ALT, Conceição CR, Khan S, Bertoli-Avella AM, Sousa AB
Clin Genet 2021 Apr;99(4):588-593. Epub 2021 Jan 20 doi: 10.1111/cge.13922. PMID: 33439489

Clinical prediction guides

Dupont J, Vieira JP, Tavares ALT, Conceição CR, Khan S, Bertoli-Avella AM, Sousa AB
Clin Genet 2021 Apr;99(4):588-593. Epub 2021 Jan 20 doi: 10.1111/cge.13922. PMID: 33439489

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