cognitive impairment

CHOPS Syndrome

Clinical Characteristics
Ocular Features: 

There is usually some degree of proptosis and apparent hypertelorism.  The eyebrows are bushy and the eyelashes are luxurious.  One of three patients had cataracts and another had mild optic atrophy.

Systemic Features: 

The overall facial appearance may resemble Cornelia de Lange syndrome with hypertrichosis and a coarse, round facies.  Head circumference is low normal.  Septal defects and a patent ductus arteriosus are often present.  Laryngeal and tracheal malacia predispose to recurrent pulmonary infections and chronic lung disease.  Skeletal dysplasia includes brachydactyly and anomalous vertebral bodies resulting in short stature (3rd percentile).  Genitourinary abnormalities include cryptorchidism, horseshoe kidney, and vesiculoureteral reflux.  Delayed gastric emptying and reflux have been reported.

Genetics

Heterozygous mutations in the AFF4 gene (5q31.1) have been identified in 3 unrelated individuals with this condition.  No familial cases have been identified.  The gene is a core component of the super elongation complex that is critical to transcriptional elongation during embryogenesis.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no treatment for the general disorder.  Tracheostomy was required in 2 of three reported patients. 

References
Article Title: 

Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin

Izumi K, Nakato R, Zhang Z, Edmondson AC, Noon S, Dulik MC, Rajagopalan R, Venditti CP, Gripp K, Samanich J, Zackai EH, Deardorff MA, Clark D, Allen JL, Dorsett D, Misulovin Z, Komata M, Bando M, Kaur M, Katou Y, Shirahige K, Krantz ID. Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. Nat Genet. 2015 Apr;47(4):338-44.

PubMed ID: 
25730767

Ataxia with Oculomotor Apraxia 4

Clinical Characteristics
Ocular Features: 

Oculomotor apraxia is usually noted after the ataxia and dystonia are apparent.

Systemic Features: 

The mean age of first symptoms is 4.3 years with dystonia being the first symptom.  Cerebellar ataxia is usually the second symptom to appear.  Cognitive impairment is present in most but not all patients with this condition.  This can progress to severe dementia in some individuals.  Dystonia may become attenuated with time.  Peripheral neuropathy with decreased vibration sense and areflexia is often present.  Cerebellar atrophy is present in all patients.

Motor difficulties such as weakness and muscle atrophy may lead to loss of independent mobility by the second to third decades.

Genetics

Homozygous or compound heterozygous mutations in the PNKP gene (19q13.33) are responsible for this disorder.

Mutations in this gene have also been associated with an infantile form of epileptic encephalopathy, microcephaly, and developmental delay (613402).

See also Ataxia with Oculomotor Apraxia 1 (208920) with hypoalbuminemia, Ataxia with Oculomotor Apraxia 2 (606002), and Ataxia with Oculomotor Apraxia 3 (615217).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no general treatment for this condition but physical therapy may be helpful in the early stages.

References
Article Title: 

Tenorio Syndrome

Clinical Characteristics
Ocular Features: 

The eyebrows appear bushy.  Inflammation of the limbus and keratoconjunctivitis sicca are often present and reported to resemble Sjogren syndrome.

Systemic Features: 

Infants appear large at birth with a large forehead and macrocephaly.  Birth weight, length, and head circumference are usually above the 97th percentile. The mandible appears large and the lips are full and ‘fleshy’.  Dentition is delayed.  Recurrent stomatitis and gastroesophageal reflux have been noted.  Closure of the fontanels is delayed.  Hypotonia and hyperflexible joints can be a feature.

Multiple brain anomalies have been described including cortical atrophy, dilated and asymmetrical ventricles, and mild hydrocephalus.  Psychomotor development and milestones are delayed.  Intellectual disabilities, syncope, hypoglycemia, seizures, apneic episodes, mood anomalies, abnormal gait, and general clumsiness may be present.  There was considerable clinical variation among the six reported patients. 

Genetics

Heterozygous mutations in RNF125 (18q12.1) are responsible for this syndrome. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

A new overgrowth syndrome is due to mutations in RNF125

Tenorio J, Mansilla A, Valencia M, Martinez-Glez V, Romanelli V, Arias P, Castrejon N, Poletta F, Guillen-Navarro E, Gordo G, Mansilla E, Garcia-Santiago F, Gonzalez-Casado I, Vallespin E, Palomares M, Mori MA, Santos-Simarro F, Garcia-Minaur S, Fernandez L, Mena R, Benito-Sanz S, del Pozo A, Silla JC, Ibanez K, Lopez-Granados E, Martin-Trujillo A, Montaner D; SOGRI Consortium, Heath KE, Campos-Barros A, Dopazo J, Nevado J, Monk D, Ruiz-Perez VL, Lapunzina P. A new overgrowth syndrome is due to mutations in RNF125. Hum Mutat. 2014 Dec;35(12):1436-41.

PubMed ID: 
25196541

Baraitser-Winter Syndrome 1

Clinical Characteristics
Ocular Features: 

Ptosis (both unilateral and bilateral), hypertelorism, prominent epicanthal folds, and colobomata are common.  The iris stroma may be dysplastic and correctopia has been observed.  Visual acuity has not been measured.

Systemic Features: 

Postnatal growth retardation leads to short stature.  Microcephaly and morphological aberrations in the brain such as lissencephaly, agenesis of the corpus callosum and pachygyria are present.  Seizures and developmental delays are common.  Hearing loss is sensorineural in type.

The ears are low-set and the posterior hair line may be low as well.  The nasal bridge appears broad and the nose appears short. Male genitalia are often underdeveloped.  Bicuspid aortic valves, patent ductus arteriosus, and aortic stenosis have been reported.

Genetics

Heterozygous mutations in the ACTB gene (7p22.1) are responsible for this apparent autosomal dominant syndrome.  However, all patients have been sporadic.

This condition is clinically similar to Baraitser-Winter syndrome 2 (614583) which is a unique entity caused by a mutation in ACTG1. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No specific treatment is available.

References
Article Title: 

New ocular finding in Baraitser-Winter syndrome

Rall N, Leon A, Gomez R, Daroca J, Lacassie Y. New ocular finding in Baraitser-Winter syndrome. Eur J Med Genet. 2017 Oct 9. pii: S1769-7212(17)30156-8. doi: 10.1016/j.ejmg.2017.10.006. [Epub ahead of print].

PubMed ID: 
29024830

Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases

Verloes A, Di Donato N, Masliah-Planchon J, Jongmans M, Abdul-Raman OA, Albrecht B, Allanson J, Brunner H, Bertola D, Chassaing N, David A, Devriendt K, Eftekhari P, Drouin-Garraud V, Faravelli F, Faivre L, Giuliano F, Guion Almeida L, Juncos J, Kempers M, Eker HK, Lacombe D, Lin A, Mancini G, Melis D, Lourenco CM, Siu VM, Morin G, Nezarati M, Nowaczyk MJ, Ramer JC, Osimani S, Philip N, Pierpont ME, Procaccio V, Roseli ZS, Rossi M, Rusu C, Sznajer Y, Templin L, Uliana V, Klaus M, Van Bon B, Van Ravenswaaij C, Wainer B, Fry AE, Rump A, Hoischen A, Drunat S, Riviere JB, Dobyns WB, Pilz DT. Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases. Eur J Hum Genet. 2014 Jul 23.

PubMed ID: 
25052316

De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome

Riviere JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat Genet. 2012 Feb 26;44(4):440-4.

PubMed ID: 
22366783

Spastic Paraplegia 7

Clinical Characteristics
Ocular Features: 

Many but not all individuals have significant visual loss due to optic atrophy.  Other ocular signs include supranuclear palsy, ptosis, and nystagmus.  Older individuals with advanced disease may have progressive external ophthalmoplegia.

Systemic Features: 

There is a great deal of clinical heterogeneity between families and not all individuals have severe neurological disease.  Progressive neurological signs (primarily abnormal gait) are often present in late childhood or early adolescence but may occur late in life.  Clinical features include muscle atrophy and weakness with spasticity (more pronounced in the lower limbs), ataxia, pyramidal signs, dysphagia, and cerebellar dysarthria.  Hyperreflexia and extensor plantar responses are often present.  Cognitive deficits are manifest as deficits in attention and higher levels of reasoning.  Some patients have a mild peripheral neuropathy with decreased vibratory sense.  Many patients have significant dysfunction of the bladder sphincter.  Adults may lose their mobility and are confined to a wheelchair.

Some patients develop scoliosis and pes cavus.  The MRI often shows cerebellar and mild frontal cortical atrophy.

Genetics

This type of spastic paraplegia results from mutations in the paraplegin gene, SPG7 (16q24.3).  It is usually transmitted in an autosomal recessive pattern although heterozygous patients with symptoms have been reported. Evidence suggests that the symptoms arise from a defect in mitochondrial respiration.

Patients with spastic paraplegia 15 (270700) have a similar neurological phenotype plus a flecked retina.  Congenital cataracts are part of the phenotype of spastic paraplegia 46 (614409).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Treatment is symptomatic.  Physical, speech, and occupational therapy may be helpful in selected patients.  Low vision aids may be of benefit in some individuals, at least early in the disease.

References
Article Title: 

Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance

Pfeffer G, Gorman GS, Griffin H, Kurzawa-Akanbi M, Blakely EL, Wilson I, Sitarz K, Moore D, Murphy JL, Alston CL, Pyle A, Coxhead J, Payne B, Gorrie GH, Longman C, Hadjivassiliou M, McConville J, Dick D, Imam I, Hilton D, Norwood F, Baker MR, Jaiser SR, Yu-Wai-Man P, Farrell M, McCarthy A, Lynch T, McFarland R, Schaefer AM, Turnbull DM, Horvath R, Taylor RW, Chinnery PF. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. Brain. 2014 Apr 10. [Epub ahead of print].

PubMed ID: 
24727571

A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia

Arnoldi A, Tonelli A, Crippa F, Villani G, Pacelli C, Sironi M, Pozzoli U, D'Angelo MG, Meola G, Martinuzzi A, Crimella C, Redaelli F, Panzeri C, Renieri A, Comi GP, Turconi AC, Bresolin N, Bassi MT. A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia. Hum Mutat. 2008 Apr;29(4):522-31.

PubMed ID: 
18200586

Joubert Syndrome and Related Disorders

Clinical Characteristics
Ocular Features: 

Ocular findings like systemic features are highly variable both within and between families.  Vision can be normal but in other patients it is severely reduced to the range of 20/200.  The pupils may respond sluggishly or even paradoxically to light.  ERG recordings have been reported to be normal in some patients, but absent or reduced in others.  The fundus appearance is often normal but in other individuals the pigmentation is mottled, the retinal arterioles are attenuated, and the macula has a cellophane maculopathy.  Drusen and colobomas are sometimes seen in the optic nerve while occasional patients have typical chorioretinal colobomas.  The eyebrows are often highly arched.

The oculomotor system is frequently involved.  Apraxia to some degree is common with most patients having difficulty with smooth pursuit and saccadic movements.  Compensatory head thrusting is often observed.  A pendular nystagmus may be present while esophoria or esotropia is present in many patients.

Systemic Features: 

There is a great deal of clinical heterogeneity in this group of ciliary dyskinesias.  Developmental delays, cognitive impairment, truncal ataxia, breathing irregularities, and behavioral disorders are among the more common features.  Hyperactivity and aggressiveness combined with dependency require constant vigilance and care.  Postaxial polydactyly is a feature of some cases.  Hypotonia is evident at birth.  Liver failure and renal disease develop in many individuals.  Neuroimaging of the midbrain-hindbrain area reveals agenesis or some degree of dysgenesis of the vermis with the 'molar tooth sign' in the isthmus region considered to be a diagnostic sign.  The fourth ventricle is usually enlarged while the cerebellar hemispheres may be hypoplastic.

The facies features are said to be distinctive in older individuals.  The face appears long with frontal prominence due to bitemporal narrowing, the nasal bridge and tip are prominent, the jaw is prominent, the lower lip protrudes, and the corners of the mouth are turned down.

Genetics

This is a clinically and genetically heterogeneous group of disorders with many overlapping features.  Most disorders in this disease category, known as JSRD, are inherited in an autosomal recessive pattern.  Mutations in at least 34 genes have been identified.  One, OFD1 (300804), is located on the X chromosome (Xp22.2).

There are significant clinical similarities to Meckel syndrome (249000) and Smith-Lemli-Opitz syndrome (270400).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Treatment is mostly for specific symptoms such as respiratory distress, renal disease, speech and physical therapy, low vision, and hepatic failure.

References
Article Title: 

Joubert Syndrome: Ophthalmological Findings in Correlation with Genotype and Hepatorenal Disease in 99 Patients Prospectively Evaluated at a Single Center

Brooks BP, Zein WM, Thompson AH, Mokhtarzadeh M, Doherty DA, Parisi M, Glass IA, Malicdan MC, Vilboux T, Vemulapalli M, Mullikin JC, Gahl WA, Gunay-Aygun M. Joubert Syndrome: Ophthalmological Findings in Correlation with Genotype and Hepatorenal Disease in 99 Patients Prospectively Evaluated at a Single Center. Ophthalmology. 2018 Jul 25. pii: S0161-6420(18)30686-9. doi: 10.1016/j.ophtha.2018.05.026. [Epub ahead of print].

PubMed ID: 
30055837

Ophthalmological findings in Joubert syndrome

Sturm V, Leiba H, Menke MN, Valente EM, Poretti A, Landau K, Boltshauser E. Ophthalmological findings in Joubert syndrome. Eye (Lond). 2010 Feb;24(2):222-5.

PubMed ID: 
19461662

Orofaciodigital Syndrome IX

Clinical Characteristics
Ocular Features: 

Multiple forms of orofaciodigital syndrome are recognized but this one (type IX, originally reported as VIII) is of ophthalmological interest because of the retinal anomalies.  Gurrieri’s original report calls these “retinochoroideal lacunae of colobomatous origin” similar to those found in Aicardi syndrome (304050).  These were further described as hypopigmented and atrophic appearing.  Synophyrs and hypertelorism have been noted and the ears may be low-set.

Systemic Features: 

Facial, oral, digital, psychomotor delays, and skeletal anomalies are major systemic features of OFD IX.  The oral manifestations include a high arched palate, cleft lip (sometimes subtle), bifid tongue, hemartomas on the tongue, abnormal tongue frenulation, and dental anomalies (supernumerary teeth).  Digital anomalies consist of mild syndactyly and occasionally polydactyly, brachydactyly, and bifid large toes.  Some patients have short stature.  Psychomotor delay is common and some patients have been described as mentally retarded.

Genetics

This is most likely an autosomal recessive condition since multiple sibs of both sexes have been identified.  Nothing is known of the locus or specific mutation.

Gurrieri’s name is attached to another syndrome (Gurrieri syndrome [601187]) with entirely different oculoskeletal features.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Specific malformations may need correction but there is no treatment for the overall disease.

References
Article Title: 

Dyskeratosis Congenita

Clinical Characteristics
Ocular Features: 

The conjunctiva and eyelids are prominently involved as part of the generalized mucocutaneous disease.  Keratinization of the lid margins, absent lacrimal puncta, trichiasis, cicatrizing conjunctivitis, entropion, ectropion, blepharitis, sparse eyelashes, and symblephara are important features.  The cornea is also involved with keratinization of the epithelial surface and vascularization.  The nasolacrimal duct is sometimes blocked.  At least one patient has been reported to have an exudative retinopathy. 

Systemic Features: 

Dyskeratosis congenita consists of a heterogeneous (genetic and clinical) group of inherited bone marrow failure and premature aging syndromes with the common feature of shortened telomeres.  There is considerable variability in the clinical features.  Prominent manifestations include nail dysplasia, oral leukoplakia, abnormal dentition, and reticulated skin pigmentation. Some patients have cognitive impairments.  Liver failure, testicular atrophy, pulmonary fibrosis, aplastic anemia, and osteoporosis along with features of aging such as premature grey hair and loss are typical.  There is an increased risk of malignancies, especially acute myelogenous leukemia.  Bone marrow failure is the major cause of early death.

Genetics

At least three autosomal dominant, three autosomal recessive, and one X-linked form of dyskeratosis congenita are recognized.  Mutations in at least 7 genes have been implicated.

Autosomal dominant disease can result from mutations in the TERC gene (DKCA1; 3q36.2; 127550), the TERT gene (DKCA2; 5p15.33; 613989), and the TINF2 gene (DKCA3; 14q12; 613990).  Mutations in the TINF2 gene are also responsible for Revesz syndrome (268130) with many features of DKC in addition to ocular findings of an exudative retinopathy resembling Coats disease.

Autosomal recessive disease is caused by mutations in the NOP10 (NOLA3) gene (DCKB1; 224230; 15q14-q15), the  NHP2 (NOLA2) gene (DKCB2; 5q35; 613987), and the WRAP53 gene (DKCB3; 17p13; 613988).  Mutations in the TERT gene may also cause autosomal recessive disease known as DKCB4 (613989).  

The X-linked disease (DKCX) (Zinsser-Engman-Cole syndrome) results from a mutation in the DKC1 gene (Xq28; 305000).  The same gene is mutated in Hoyeraal-Hreidarsson syndrome (300240) which some consider to be a more severe variant of dyskeratosis congenita with the added features of immunodeficiency, microcephaly, growth and mental retardation, and cerebellar hypoplasia. 

The majority of mutations occur in genes that provide instructions for making proteins involved in maintainence of telemeres located at the ends of chromosomes.  Shortened telomeres can result from maintainence deficiencies although the molecular mechanism(s) remain elusive.

Pedigree: 
Autosomal dominant
Autosomal recessive
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

Treatment for DKC with hematopoietic stem cell transplantation can be curative but its long-term efficacy is poor.  Some advocate androgen therapy first.  Lifelong cancer surveillance and frequent ocular and dental evaluations are important with specific treatment as indicated.

References
Article Title: 

Smith-Magenis Syndrome

Clinical Characteristics
Ocular Features: 

Ocular abnormalities have been found in the majority of patients.  Microcornea, myopia, strabismus and iris dysplasia are the most common.  Rare patients have iris colobomas or correctopia.  The eyes appear deep-set and lid fissures are upward slanting.

Systemic Features: 

The facial features are considered to be distinctive, characterized by a broad, square face, prominent forehead, broad nasal bridge, and midface hypoplasia.  These and other features appear more pronounced with age as in the size of the jaw which is underdeveloped in infancy and eventually becomes prognathic.  Most patients have developmental delays, speech and motor deficits, cognitive impairments and behavioral abnormalities.  Hypotonia, hyporeflexia, failure to thrive, lethargy, and feeding difficulties are common in infants.  Older individuals have REM sleep disturbances with self-destructive behaviors, aggression, inattention, hyperactivity, and impulsivity.  Short stature, hypodontia, brachydactyly, hearing loss, laryngeal anomalies, and peripheral neuropathy are common. Seizures are uncommon.

The behavioral profile of this syndrome can resemble that of autism spectrum disorders although symptoms of compulsivity are more mild.

A related developmental disorder known as Potacki-Lupski syndrome (610883) involving the same locus on chromosome 17 has a similar behavioral profile.  Ocular and systemic malformations may be less severe though.

Genetics

Most patients (90%) with the Smith-Magenis syndrome have interstitial deletions in the short arm of chromosome 17 (17p11.2).  However, it is included here since a few have heterozygous molecular mutations in the RAI1 gene which is located in this region.  While there is considerable phenotypic overlap, individuals with chromosomal deletions have the more severe phenotype as might be expected.  For example, those with RAI1 mutations tend to be obese and are less likely to exhibit short stature, cardiac anomalies, hypotonia, hearing loss and motor delays than seen in patients with a deletion in chromosome 17.  However, the phenotype is highly variable among patients with deletions depending upon the nature and size of the deletion.

The retinoic acid induced 1 gene (RAI1) codes for a transcription factor whose activity is reduced by mutations within it.

Familial cases are rare and reproductive fitness is virtually zero.  If parental chromosomes are normal, the risk for recurrence in sibs is less than 1%.  Males and females are equally affected.

In Potocki-Lupski syndrome (610883) there is duplication of the 17p11.2 microdeletion as the reciprocal recombination product of the SMS deletion.   

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Medical monitoring, psychotropic medications and behavioral therapies are all useful.  Special education and vocational training may be helpful for those less severely affected.

References
Article Title: 

Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and

Potocki L, Bi W, Treadwell-Deering D, Carvalho CM, Eifert A, Friedman EM,
Glaze D, Krull K, Lee JA, Lewis RA, Mendoza-Londono R, Robbins-Furman P, Shaw C,
Shi X, Weissenberger G, Withers M, Yatsenko SA, Zackai EH, Stankiewicz P, Lupski
JR. Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and
delineation of a dosage-sensitive critical interval that can convey an autism
phenotype. Am J Hum Genet. 2007 Apr;80(4):633-49.

PubMed ID: 
17357070

Apert Syndrome

Clinical Characteristics
Ocular Features: 

In 10% of patients, keratitis and corneal scarring occur from the sometimes marked proptosis and corneal exposure.  Optic atrophy is present in over 20% of patients.  Strabismus, primarily exotropia, is found in more than 70% and various extraocular muscle anomalies may be detectable.  Usually the exotropia has a V-pattern with overaction of the inferior oblique muscles while the superior oblique is weak.  Amblyopia occurs in nearly 20%.  The lid fissures often slant downward and the eyebrows may be interrupted.

Systemic Features: 

This brachysphenocephalic type of acrocephaly is associated with syndactyly in the hands and feet.  Pre- and postaxial polydactyly may be present.  There is considerable variation in expression with some patients so mildly affected that they appear virtually normal, whereas others have extreme degrees of brachycephaly with high foreheads, midface hypoplasia, and proptosis secondary to shallow orbits.  Imaging often reveals one or more CNS anomalies such as defects of the corpus callosum, partial absence of the septum pellucidum, ventriculomegaly, and sometimes hydrocephalus.  A small but significant proportion of patients have some developmental delay and cognitive impairment.  Over 39% of patients have a normal IQ.

Genetics

This type of craniosynostosis is caused by mutations in the fibroblast growth factor receptor-2 gene, FGFR2, located at 10q26.13.  It is generally considered an autosomal dominant disorder based on familial cases but most occur sporadically.  A paternal age effect on mutations has been found.  The same gene is mutant in allelic disorders sometimes clinically separated and labeled Crouzon (123500) and Pfeiffer (some cases) (101600) syndromes.  Jackson-Weiss syndrome (123150) maps to the same locus.  However, this entire group has many overlapping features making classification on clinical grounds alone difficult.  Only Apert syndrome is caused by mutations in a single gene whereas other syndromes seem to result from mutations in multiple genes.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No specific treatment is available for this disorder but exposure keratitis may require surveillance and therapy.

References
Article Title: 

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