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Agnathia-otocephaly complex(AGOTC)

MedGen UID:
78541
Concept ID:
C0265242
Congenital Abnormality
Synonyms: Agnathia-holoprosencephaly; Dysgnathia complex; DYSGNATHIA COMPLEX AGNATHIA-HOLOPROSENCEPHALY; OTOCEPHALY
SNOMED CT: Otocephalic syndrome (48180002); Otocephaly (48180002); Otocephalus (48180002)
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).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): PRRX1 (1q24.2)
 
Monarch Initiative: MONDO:0008740
OMIM®: 202650
Orphanet: ORPHA990

Definition

Agnathia-otocephaly (AGOTC) is a rare condition characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular anomalies, and situs inversus have been reported. The disorder is almost always lethal (review by Faye-Petersen et al., 2006). [from OMIM]

Clinical features

From HPO
Atrial septal defect, ostium secundum type
MedGen UID:
91034
Concept ID:
C0344724
Congenital Abnormality
A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum.
Situs inversus
MedGen UID:
1642262
Concept ID:
C4551493
Congenital Abnormality
A left-right reversal (or mirror reflection) of the anatomical location of the major thoracic and abdominal organs.
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Synotia
MedGen UID:
451028
Concept ID:
C0266677
Congenital Abnormality
A congenital malformation characterized by the union or approximation of the ears in front of the neck, often accompanied by the absence or defective development of the lower jaw.
Holoprosencephaly sequence
MedGen UID:
38214
Concept ID:
C0079541
Congenital Abnormality
Nonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. This condition is called nonsyndromic to distinguish it from other types of holoprosencephaly caused by genetic syndromes, chromosome abnormalities, or substances that cause birth defects (teratogens). The severity of nonsyndromic holoprosencephaly varies widely among affected individuals, even within the same family.\n\nNonsyndromic holoprosencephaly can be grouped into four types according to the degree of brain division. From most to least severe, the types are known as alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In the most severe forms of nonsyndromic holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe nonsyndromic holoprosencephaly die before birth or soon after. In the less severe forms, the brain is partially divided and the eyes are usually set close together (hypotelorism). The life expectancy of these affected individuals varies depending on the severity of symptoms.\n\nPeople with nonsyndromic holoprosencephaly often have a small head (microcephaly), although they can develop a buildup of fluid in the brain (hydrocephalus) that causes increased head size (macrocephaly). Other features may include an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip), one central front tooth instead of two (a single maxillary central incisor), and a flat nasal bridge. The eyeballs may be abnormally small (microphthalmia) or absent (anophthalmia).\n\nSome individuals with nonsyndromic holoprosencephaly have a distinctive pattern of facial features, including a narrowing of the head at the temples, outside corners of the eyes that point upward (upslanting palpebral fissures), large ears, a short nose with upturned nostrils, and a broad and deep space between the nose and mouth (philtrum). In general, the severity of facial features is directly related to the severity of the brain abnormalities. However, individuals with mildly affected facial features can have severe brain abnormalities. Some people do not have apparent structural brain abnormalities but have some of the facial features associated with this condition. These individuals are considered to have a form of the disorder known as microform holoprosencephaly and are typically identified after the birth of a severely affected family member.\n\nMost people with nonsyndromic holoprosencephaly have developmental delay and intellectual disability. Affected individuals also frequently have a malfunctioning pituitary gland, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. Most commonly, people with nonsyndromic holoprosencephaly and pituitary dysfunction develop diabetes insipidus, a condition that disrupts the balance between fluid intake and urine excretion. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature, heart rate, and breathing. The sense of smell may be diminished (hyposmia) or completely absent (anosmia) if the part of the brain that processes smells is underdeveloped or missing.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Mandibular aplasia
MedGen UID:
672709
Concept ID:
C0685776
Congenital Abnormality
Absence of the mandible.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Laryngeal hypoplasia
MedGen UID:
96567
Concept ID:
C0431527
Congenital Abnormality
Underdevelopment of the larynx.
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
Tracheomalacia
MedGen UID:
215296
Concept ID:
C0948187
Disease or Syndrome
Congenital tracheomalacia is a rare condition where the trachea is soft and flexible causing the tracheal wall to collapse when exhaling, coughing or crying, that usually presents in infancy, and that is characterized by stridor and noisy breathing or upper respiratory infections. Tracheomalacia improves by the age of 18-24 months.
Hypoplasia of the epiglottis
MedGen UID:
235600
Concept ID:
C1396772
Congenital Abnormality
Hypoplasia of the epiglottis.
Microglossia
MedGen UID:
10029
Concept ID:
C0025988
Congenital Abnormality
Decreased length and width of the tongue.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Aglossia
MedGen UID:
57859
Concept ID:
C0158663
Congenital Abnormality
Absence of the tongue owing to a developmental abnormality.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Wide nose
MedGen UID:
140869
Concept ID:
C0426421
Finding
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Abnormality of the eye
MedGen UID:
1370071
Concept ID:
C4316870
Anatomical Abnormality
Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Professional guidelines

PubMed

Ibba RM, Zoppi MA, Floris M, Putzolu M, Monni G, Todde PF, Sardu G
Am J Med Genet 2000 Feb 28;90(5):427-9. PMID: 10706365

Recent clinical studies

Etiology

Suemitsu T, Takesawa A, Hosokawa M, Mitani T, Kadooka M, Furusawa Y, Kawataki M, Dohi S
Am J Case Rep 2023 May 11;24:e939016. doi: 10.12659/AJCR.939016. PMID: 37165610Free PMC Article
El-Dessouky SH, Aboulghar MM, Gaafar HM, Abdella RM, Sharaf MF, Ateya MI, Elarab AE, Zidan WH, Helal RM, Aboelsaud SM, Eid MM, Abdel-Salam GMH
Prenat Diagn 2020 Apr;40(5):565-576. Epub 2020 Feb 10 doi: 10.1002/pd.5649. PMID: 31955448
Rodriguez N, Casasbuenas A, Andreeva E, Odegova N, Wong AE, Sepulveda W
J Ultrasound Med 2019 Mar;38(3):805-809. Epub 2018 Aug 31 doi: 10.1002/jum.14759. PMID: 30171631
Golinko MS, Shetye P, Flores RL, Staffenberg DA
J Craniofac Surg 2015 Nov;26(8):2387-92. doi: 10.1097/SCS.0000000000002150. PMID: 26517463

Diagnosis

Dubucs C, Chassaing N, Sergi C, Aubert-Mucca M, Attié-Bitach T, Lacombe D, Thauvin-Robinet C, Arpin S, Perez MJ, Cabrol C, Chen CP, Aziza J, Colin E, Martinovic J, Calvas P, Plaisancié J
Clin Oral Investig 2021 Mar;25(3):1353-1362. Epub 2020 Jul 9 doi: 10.1007/s00784-020-03443-w. PMID: 32643087
Gonzalez SR, Jones JK, Golinko MS
J Craniofac Surg 2020 Jan/Feb;31(1):e84-e89. doi: 10.1097/SCS.0000000000005945. PMID: 31634311
Rodriguez N, Casasbuenas A, Andreeva E, Odegova N, Wong AE, Sepulveda W
J Ultrasound Med 2019 Mar;38(3):805-809. Epub 2018 Aug 31 doi: 10.1002/jum.14759. PMID: 30171631
Golinko MS, Shetye P, Flores RL, Staffenberg DA
J Craniofac Surg 2015 Nov;26(8):2387-92. doi: 10.1097/SCS.0000000000002150. PMID: 26517463
Sergouniotis PI, Urquhart JE, Williams SG, Bhaskar SS, Black GC, Lovell SC, Whitby DJ, Newman WG, Clayton-Smith J
J Hum Genet 2015 Apr;60(4):199-202. Epub 2015 Jan 15 doi: 10.1038/jhg.2014.122. PMID: 25589041

Therapy

Khan A, Bourgeois J, Mohide P
Clin Dysmorphol 2008 Jan;17(1):75-76. doi: 10.1097/MCD.0b013e3282f16979. PMID: 18049088

Prognosis

Suemitsu T, Takesawa A, Hosokawa M, Mitani T, Kadooka M, Furusawa Y, Kawataki M, Dohi S
Am J Case Rep 2023 May 11;24:e939016. doi: 10.12659/AJCR.939016. PMID: 37165610Free PMC Article
Sergouniotis PI, Urquhart JE, Williams SG, Bhaskar SS, Black GC, Lovell SC, Whitby DJ, Newman WG, Clayton-Smith J
J Hum Genet 2015 Apr;60(4):199-202. Epub 2015 Jan 15 doi: 10.1038/jhg.2014.122. PMID: 25589041

Clinical prediction guides

Sergouniotis PI, Urquhart JE, Williams SG, Bhaskar SS, Black GC, Lovell SC, Whitby DJ, Newman WG, Clayton-Smith J
J Hum Genet 2015 Apr;60(4):199-202. Epub 2015 Jan 15 doi: 10.1038/jhg.2014.122. PMID: 25589041

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