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Acrocephalosyndactyly type I(ACS1)

MedGen UID:
7858
Concept ID:
C0001193
Congenital Abnormality
Synonyms: Acrocephalo-syndactyly type 1; ACS 1; Apert syndrome; FGFR2-Related Craniosynostosis; Syndactylic oxycephaly
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, 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.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Acrocephalosyndactyly type I (205258009); Apert syndrome (205258009); Acrocephalosyndactyly (Apert) (205258009)
 
Gene (location): FGFR2 (10q26.13)
OMIM®: 101200
Orphanet: ORPHA87

Definition

The eight disorders comprising the FGFR-related craniosynostosis spectrum are Pfeiffer syndrome, Apert syndrome, Crouzon syndrome, Beare-Stevenson syndrome, FGFR2-related isolated coronal synostosis, Jackson-Weiss syndrome, Crouzon syndrome with acanthosis nigricans (AN), and Muenke syndrome (isolated coronal synostosis caused by the p.Pro250Arg pathogenic variant in FGFR3). Muenke syndrome and FGFR2-related isolated coronal synostosis are characterized only by uni- or bicoronal craniosynostosis; the remainder are characterized by bicoronal craniosynostosis or cloverleaf skull, distinctive facial features, and variable hand and foot findings. [from GeneReviews]

Additional descriptions

From OMIM
Apert syndrome is a congenital disorder characterized primarily by craniosynostosis, midface hypoplasia, and syndactyly of the hands and feet with a tendency to fusion of bony structures. Most cases are sporadic, but autosomal dominant inheritance has been reported (Mantilla-Capacho et al., 2005). Cohen (1973) provided a review of all the 'craniosynostosis syndromes.'  http://www.omim.org/entry/101200
From GHR
Apert syndrome is a genetic disorder characterized by skeletal abnormalities. A key feature of Apert syndrome is the premature closure of the bones of the skull (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. In addition, a varied number of fingers and toes are fused together (syndactyly).Craniosynostosis causes many of the characteristic facial features of Apert syndrome. Premature fusion of the skull bones prevents the head from growing normally, which leads to a sunken appearance in the middle of the face (midface hypoplasia), a beaked nose, a wrinkled forehead, and an opening in the roof of the mouth (a cleft palate). In individuals with Apert syndrome, an underdeveloped upper jaw can lead to dental problems, such as missing teeth, irregular tooth enamel, and crowded teeth.Many individuals with Apert syndrome have vision problems due to eye abnormalities, which can include bulging eyes (exophthalmos), wide-set eyes (hypertelorism), outside corners of the eyes that point downward (downslanting palpebral fissures), eyes that do not look in the same direction (strabismus), and shallow eye sockets (ocular proptosis). Some people with Apert syndrome have hearing loss or recurrent ear infections due to malformed ear structures.Abnormal development of structures in the face and head can also cause partial blockage of the airways and lead to breathing difficulties in people with Apert syndrome. Craniosynostosis also affects development of the brain, which can disrupt intellectual development. Cognitive abilities in people with Apert syndrome range from normal to mild or moderate intellectual disability.Individuals with Apert syndrome have syndactyly of the fingers and toes. The severity of the fusion varies, although the hands tend to be more severely affected than the feet. Most commonly, three digits on each hand and foot are fused together. In the most severe cases, all of the fingers and toes are fused. Rarely, people with Apert syndrome may have extra fingers or toes (polydactyly). Some people with Apert syndrome have abnormalities in the bones of the elbows or shoulders. These bone problems can restrict movement and impede everyday activities. In some people, abnormalities occur in both sides of the body, but in others, only one side is affected.Additional signs and symptoms of Apert syndrome can include unusually heavy sweating (hyperhidrosis), oily skin with severe acne, or patches of missing hair in the eyebrows.  https://ghr.nlm.nih.gov/condition/apert-syndrome

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Abnormal enlargement or swelling of a KIDNEY due to dilation of the KIDNEY CALICES and the KIDNEY PELVIS. It is often associated with obstruction of the URETER or chronic kidney diseases that prevents normal drainage of urine into the URINARY BLADDER.
Vaginal atresia
MedGen UID:
232948
Concept ID:
C1321884
Congenital Abnormality
Congenital occlusion of the vagina or adhesion of the walls of the vagina causing occlusion.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
Developmental abnormalities in any portion of the VENTRICULAR SEPTUM resulting in abnormal communications between the two lower chambers of the heart. Classification of ventricular septal defects is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect.
Overriding aorta
MedGen UID:
120559
Concept ID:
C0265886
Congenital Abnormality
A congenital anatomic anomaly in which the aorta is positioned directly above a ventricular septal defect, thus receiving blood from both the right and left ventricles, resulting in an overall decrease In oxygenated haemoglobin and tissue cyanosis.
Growth abnormality
MedGen UID:
808205
Concept ID:
C0262361
Finding
Esophageal atresia
MedGen UID:
4545
Concept ID:
C0014850
Congenital Abnormality
A congenital abnormality of the esophagus in which the upper esophagus ends as a blind pouch and does not connect with the lower esophagus; it is often accompanied by a tracheoesophageal fistula. Signs and symptoms in a newborn with this abnormality include excessive salivation, choking, coughing, and the development of cyanosis and respiratory distress when fed.
Pyloric stenosis
MedGen UID:
18780
Concept ID:
C0034194
Pathologic Function
Narrowing of the pyloric canal with varied etiology. A common form is due to muscle hypertrophy (PYLORIC STENOSIS, HYPERTROPHIC) seen in infants.
Ectopic anus
MedGen UID:
75606
Concept ID:
C0266231
Congenital Abnormality
Abnormal displacement or malposition of the anus.
Chronic otitis media
MedGen UID:
75751
Concept ID:
C0271441
Disease or Syndrome
Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A general term for the complete or partial loss of the ability to hear from one or both ears.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
A disorder characterized by an abnormal increase of cerebrospinal fluid in the ventricles of the brain.
Arachnoid cyst
MedGen UID:
86860
Concept ID:
C0078981
Disease or Syndrome
An intracranial or spinal cyst which contains fluid and is composed of arachnoid cells. Intracranial arachnoid cysts may present with headaches, seizures and hydrocephalus. Spinal arachnoid cysts may present with symptoms of radiculopathy.
Corpus callosum agenesis
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.
Absent septum pellucidum
MedGen UID:
96561
Concept ID:
C0431371
Congenital Abnormality
Absence of the septum pellucidum.
Chiari malformation type I
MedGen UID:
196689
Concept ID:
C0750929
Congenital Abnormality
Chiari malformation type I (CM1) is the protrusion of the cerebellar tonsils through the foramen magnum, defined radiologically as tonsillar descent of 5 mm or more. CM1 is associated with syringomyelia (see 186700) in up to 80% of cases. Although many individuals with CM1 are asymptomatic, the malformation can cause headaches, ocular disturbances, otoneurologic disturbances, lower cranial nerve signs, cerebellar ataxia, or spasticity. Onset of symptoms is usually in the third decade of life (Speer et al., 2003). Since many cases of CM1 are asymptomatic, prevalence estimates may not be accurate. However, a retrospective investigation of brain MRIs reported the prevalence of CM1 to be 1 in 1,280 individuals (Meadows et al., 2000).
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Posterior fossa cyst
MedGen UID:
341753
Concept ID:
C1857353
Finding
A discrete posterior fossa cerebrospinal fluid (CSF) collection that does not communicate directly with the fourth ventricle.
Abnormal morphology of the limbic system
MedGen UID:
400282
Concept ID:
C1863392
Finding
Any structural anomaly of the limbic system, a set of midline structures surrounding the brainstem of the mammalian brain, originally described anatomically, e.g., hippocampal formation, amygdala, hypothalamus, cingulate cortex. Although the original designation was anatomical, the limbic system has come to be associated with the system in the brain subserving emotional functions. As such, it is very poorly defined and doesn't correspond closely to the anatomical meaning any longer. [BirnLex].
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Megalencephaly
MedGen UID:
812057
Concept ID:
C3805727
Disease or Syndrome
Primary megalencephaly is defined as a head circumference about the 98th percentile that most likely is due to brain enlargement and is not secondary to disease (review by Petersson et al., 1999).
Postaxial hand polydactyly
MedGen UID:
609221
Concept ID:
C0431904
Congenital Abnormality
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Preaxial hand polydactyly
MedGen UID:
237235
Concept ID:
C1395852
Congenital Abnormality
Supernumerary digits located at the radial side of the hand. Polydactyly (supernumerary digits) involving the thumb occurs in many distinct forms of high variability and severity. Ranging from fleshy nubbins over varying degrees of partial duplication/splitting to completely duplicated or even triplicated thumbs or preaxial (on the radial side of the hand) supernumerary digits.
Synostosis of carpal bones
MedGen UID:
322856
Concept ID:
C1836193
Finding
Broad distal phalanx of the thumb
MedGen UID:
350887
Concept ID:
C1863402
Finding
Increased width of the distal phalanx of thumb.
Broad distal hallux
MedGen UID:
350166
Concept ID:
C1863403
Finding
Humeroradial synostosis
MedGen UID:
418931
Concept ID:
C2930865
Disease or Syndrome
An abnormal osseous union (fusion) between the radius and the humerus.
Cutaneous finger syndactyly
MedGen UID:
866898
Concept ID:
C4021254
Congenital Abnormality
A soft tissue continuity in the A/P axis between two fingers that extends distally to at least the level of the proximal interphalangeal joints, or a soft tissue continuity in the A/P axis between two fingers that lies significantly distal to the flexion crease that overlies the metacarpophalangeal joint of the adjacent fingers.
Anomalous tracheal cartilage
MedGen UID:
400285
Concept ID:
C1863406
Finding
An abnormality of the C-shaped rings of hyaline cartilage, normally 16 to 20 in number, that occupy the anterior two-thirds of the circumference of the trachea (the posterior portion of the ring is completed by fibrous and smooth muscle tissue).
Chronic otitis media
MedGen UID:
75751
Concept ID:
C0271441
Disease or Syndrome
Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.
Acne
MedGen UID:
152379
Concept ID:
C0702166
Disease or Syndrome
A skin condition in which there is an increase in sebum secretion by the pilosebaceous apparatus associated with open comedones (blackheads), closed comedones (whiteheads), and pustular nodules (papules, pustules, and cysts).
Delayed cranial suture closure
MedGen UID:
75805
Concept ID:
C0277828
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Postaxial hand polydactyly
MedGen UID:
609221
Concept ID:
C0431904
Congenital Abnormality
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Large fontanelles
MedGen UID:
105329
Concept ID:
C0456132
Finding
Preaxial hand polydactyly
MedGen UID:
237235
Concept ID:
C1395852
Congenital Abnormality
Supernumerary digits located at the radial side of the hand. Polydactyly (supernumerary digits) involving the thumb occurs in many distinct forms of high variability and severity. Ranging from fleshy nubbins over varying degrees of partial duplication/splitting to completely duplicated or even triplicated thumbs or preaxial (on the radial side of the hand) supernumerary digits.
Synostosis of carpal bones
MedGen UID:
322856
Concept ID:
C1836193
Finding
Coronal craniosynostosis
MedGen UID:
344694
Concept ID:
C1856266
Disease or Syndrome
Premature closure of the coronal suture of skull.
Posterior fossa cyst
MedGen UID:
341753
Concept ID:
C1857353
Finding
A discrete posterior fossa cerebrospinal fluid (CSF) collection that does not communicate directly with the fourth ventricle.
Brachyturricephaly
MedGen UID:
387833
Concept ID:
C1857484
Finding
Abnormal vertical height of the skull and a shortening of its anterior-posterior length, frequently combined with malformations of the occipital region.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Anatomical Abnormality
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Acrobrachycephaly
MedGen UID:
350164
Concept ID:
C1863395
Congenital Abnormality
An abnormality of head shape characterized by the presence of a short, wide head as well as a pointy or conical form of the top of the head owing to premature closure of the coronal and lambdoid sutures.
Broad distal phalanx of the thumb
MedGen UID:
350887
Concept ID:
C1863402
Finding
Increased width of the distal phalanx of thumb.
Broad distal hallux
MedGen UID:
350166
Concept ID:
C1863403
Finding
Shallow orbits
MedGen UID:
351328
Concept ID:
C1865244
Finding
Reduced depth of the orbits associated with prominent-appearing ocular globes.
Humeroradial synostosis
MedGen UID:
418931
Concept ID:
C2930865
Disease or Syndrome
An abnormal osseous union (fusion) between the radius and the humerus.
Cutaneous finger syndactyly
MedGen UID:
866898
Concept ID:
C4021254
Congenital Abnormality
A soft tissue continuity in the A/P axis between two fingers that extends distally to at least the level of the proximal interphalangeal joints, or a soft tissue continuity in the A/P axis between two fingers that lies significantly distal to the flexion crease that overlies the metacarpophalangeal joint of the adjacent fingers.
Cervical C5/C6 vertebrae fusion
MedGen UID:
870841
Concept ID:
C4025301
Anatomical Abnormality
Fusion of the C5 and C6 cervical vertebrae.
Choanal atresia
MedGen UID:
3395
Concept ID:
C0008297
Congenital Abnormality
A congenital abnormality that is characterized by a blocked CHOANAE, the opening between the nose and the NASOPHARYNX. Blockage can be unilateral or bilateral; bony or membranous.
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
An inherited or acquired dental abnormality characterized by improper alignment of the teeth.
Delayed eruption of teeth
MedGen UID:
68678
Concept ID:
C0239174
Finding
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Delayed cranial suture closure
MedGen UID:
75805
Concept ID:
C0277828
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Large fontanelles
MedGen UID:
105329
Concept ID:
C0456132
Finding
Choanal stenosis
MedGen UID:
108427
Concept ID:
C0584837
Finding
Abnormal narrowing of the choana (the posterior nasal aperture).
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).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
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.
Flat face
MedGen UID:
342829
Concept ID:
C1853241
Finding
Absence of concavity or convexity of the face when viewed in profile.
Coronal craniosynostosis
MedGen UID:
344694
Concept ID:
C1856266
Disease or Syndrome
Premature closure of the coronal suture of skull.
Posterior fossa cyst
MedGen UID:
341753
Concept ID:
C1857353
Finding
A discrete posterior fossa cerebrospinal fluid (CSF) collection that does not communicate directly with the fourth ventricle.
Brachyturricephaly
MedGen UID:
387833
Concept ID:
C1857484
Finding
Abnormal vertical height of the skull and a shortening of its anterior-posterior length, frequently combined with malformations of the occipital region.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Anatomical Abnormality
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Acrobrachycephaly
MedGen UID:
350164
Concept ID:
C1863395
Congenital Abnormality
An abnormality of head shape characterized by the presence of a short, wide head as well as a pointy or conical form of the top of the head owing to premature closure of the coronal and lambdoid sutures.
Shallow orbits
MedGen UID:
351328
Concept ID:
C1865244
Finding
Reduced depth of the orbits associated with prominent-appearing ocular globes.
Midface retrusion
MedGen UID:
388629
Concept ID:
C2673410
Finding
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).
Cleft uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Acne
MedGen UID:
152379
Concept ID:
C0702166
Disease or Syndrome
A skin condition in which there is an increase in sebum secretion by the pilosebaceous apparatus associated with open comedones (blackheads), closed comedones (whiteheads), and pustular nodules (papules, pustules, and cysts).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (145410), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Shallow orbits
MedGen UID:
351328
Concept ID:
C1865244
Finding
Reduced depth of the orbits associated with prominent-appearing ocular globes.

Professional guidelines

PubMed

Toriello HV, Meck JM; Professional Practice and Guidelines Committee.
Genet Med 2008 Jun;10(6):457-60. doi: 10.1097/GIM.0b013e318176fabb. PMID: 18496227Free PMC Article

Recent clinical studies

Etiology

Huang F, Sweet R, Tewfik TL
Int J Pediatr Otorhinolaryngol 2004 Apr;68(4):495-501. doi: 10.1016/j.ijporl.2003.11.010. PMID: 15013619

Diagnosis

Albuquerque MA, Cavalcanti MG
Braz Oral Res 2004 Jan-Mar;18(1):35-9. Epub 2004 Jul 20 doi: /S1517-74912004000100007. PMID: 15273784
Singh SK, Chaturvedi R, Pal SK, Singh KK, Sinha SK, Singh SK, Agrawal JK
J Assoc Physicians India 1999 Aug;47(8):842-3. PMID: 10778643
Lefort G, Sarda P, Humeau C, Rieu D
Genet Couns 1992;3(2):107-9. PMID: 1642807
Mixter RC, David DJ, Perloff WH, Green CG, Pauli RM, Popic PM
Plast Reconstr Surg 1990 Sep;86(3):457-63. doi: 10.1097/00006534-199009000-00011. PMID: 2385663

Prognosis

Ludwig K, Salmaso R, Manara R, Cosmi E, Baldi M, Rugge M
Fetal Pediatr Pathol 2012 Dec;31(6):410-4. Epub 2012 Mar 23 doi: 10.3109/15513815.2012.659407. PMID: 22443264

Clinical prediction guides

Albuquerque MA, Cavalcanti MG
Braz Oral Res 2004 Jan-Mar;18(1):35-9. Epub 2004 Jul 20 doi: /S1517-74912004000100007. PMID: 15273784

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