scoliosis

Kabuki Syndrome 1

Clinical Characteristics
Ocular Features: 

The facial features and specifically the periocular anomalies are diagnostic and responsible for the eponymic designation (resembling the make-up of actors of a Japanese theatrical form known as Kabuki). The lid fissures are long and narrow and the lateral third of the lower lids are often everted.  The eyebrows are highly-arched and broad with some sparsity especially in the lateral portion.  The eyelashes are thick and ptosis is often noted. Strabismus may be present.  Blue sclerae have been reported.

Some patients may have extreme microphthalmia.

Systemic Features: 

Post-natal growth delay and short stature are present as a result of anomalies in the vertebrae often with secondary scoliosis.  Persistence of the fetal fingertip pads is common. Hypotonia and joint hypermobility have been noted and some degree of intellectual disability is common.  Seizures have been reported but these are not common. Cleft lip and palate are seen in about a third of patients and the palate is highly arched in about 75%.  The teeth are small, frequently malformed and widely spaced.  Feeding difficulties are common.  Anal anomalies such as imperforate anus, anovestibular fistulas, and an anteriorly placed opening may be present, especially in females.  A small penis, hypospadias, and cryptorchidism are common in males.

An ill-defined immune deficit seems to be a common feature as evident by susceptibility to infections, primarily otitis media in infants and later recurrent sinopulmonary infections.   The majority of patients have hypogammaglobulinemia with a variable pattern of antibody abnormalities resembling common variable immune deficiency and especially low levels of serum IgA.  

Hearing loss is seen in nearly half of patients, some of which is no doubt due to recurrent otitis media but CT radiography has demonstrated dysplastic morphology of inner ear structures and the petrous bone.  The ears are large and cupped and preauricular pits may be present as well.

Biliary atresia and a variety of morphological anomalies of the kidney have been reported.  Renal failure can occur.  Perhaps as many as 58% of patients have congenital heart defects, mostly septal in location. 

Genetics

Heterozygous mutations in KMT2D (12q13.12) (also called MLL2) are responsible for Kabuki syndrome 1 but parental transmission to offspring is rare and the majority of patients occur sporadically.  There is also an X-linked form (Kabuki 2) caused by mutations in KDM5A (Xp11.3).  Insufficient clinical data regarding the X-linked phenotype so far has precluded the ability to distinguish the two disorders without genotyping.

Residual genetic heterogeneity remains, however, as a substantial proportion of patients do not have mutations in the two mutant genes known.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no general treatment for this condition.  Management guidelines are available (Management of Kabuki Syndrome).

References
Article Title: 

MLL2 and KDM6A mutations in patients with Kabuki syndrome

Miyake N, Koshimizu E, Okamoto N, Mizuno S, Ogata T, Nagai T, Kosho T, Ohashi H, Kato M, Sasaki G, Mabe H, Watanabe Y, Yoshino M, Matsuishi T, Takanashi J, Shotelersuk V, Tekin M, Ochi N, Kubota M, Ito N, Ihara K, Hara T, Tonoki H, Ohta T, Saito K, Matsuo M, Urano M, Enokizono T, Sato A, Tanaka H, Ogawa A, Fujita T, Hiraki Y, Kitanaka S, Matsubara Y, Makita T, Taguri M, Nakashima M, Tsurusaki Y, Saitsu H, Yoshiura K, Matsumoto N, Niikawa N. MLL2 and KDM6A mutations in patients with Kabuki syndrome. Am J Med Genet A. 2013 Sep;161A(9):2234-43. 

PubMed ID: 
23913813

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

Chorioretinopathy with Microcephaly 2

Clinical Characteristics
Ocular Features: 

Microphthalmia and microcornea are seen in most individuals and one patient had unilateral clinical anophthalmia. Hyperopia and cataracts may be present. Nystagmus is common.  One patient had a corneal opacity.  The chorioretinopathy has not been described beyond evidence of the maculopathy, attenuated retinal vessels, and occasionally hyperpigmented zones.  The ERG is either not recordable or consistent with a severe rod-cone dystrophy.  Vitreous inclusions and a 'vitreoretinal dystrophy' with falciform retinal folds were noted in several patients.  A traction detachment was present in one and bilateral serous detachments were noted in another.

Systemic Features: 

Patients have mild to severe microcephaly (up to -15 SD) with psychomotor delays.  Profound intellectual disability is a consistent feature.  Physical growth is retarded and patients have shortness of stature.  Most patients are unable to sit, stand, or walk unassisted.  One patient died at 5.5 years of age while another was alive at 20 years of age.  Rare patients may have hearing loss and seizures.

Scoliosis, kyphosis, and lordosis may be seen while  other skeletal malformations seem to occur sporadically e.g., triphalangeal thumbs, brachydactyly, postaxial polydactyly, and restricted large joint motion.  

The forehead slopes markedly.  Neuroimaging shows a consistent reduction in cortex size with simple gyral folding while the cerebellum and the brain stem are also small.  Subarachnoid cysts have been noted in several patients and the corpus callosum may be short or otherwise malformed.

Genetics

Homozygous mutations in the PLK4 gene (4q28.2) segregate with this condition.  Its product localizes to centrioles and plays a central role in centriole duplication.

For a somewhat similar condition but without the sloping forhead see Chorioretinoapathy with Microcephaly 1 (251270) but resulting from homozygous mutations in TUBGCP6.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is know.

References
Article Title: 

Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy

Martin CA, Ahmad I, Klingseisen A, Hussain MS, Bicknell LS, Leitch A, Nurnberg G, Toliat MR, Murray JE, Hunt D, Khan F, Ali Z, Tinschert S, Ding J, Keith C, Harley ME, Heyn P, Muller R, Hoffmann I, Daire VC, Dollfus H, Dupuis L, Bashamboo A, McElreavey K, Kariminejad A, Mendoza-Londono R, Moore AT, Saggar A, Schlechter C, Weleber R, Thiele H, Altmuller J, Hohne W, Hurles ME, Noegel AA, Baig SM, Nurnberg P, Jackson AP. Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat Genet. 2014 Dec;46(12):1283-92.

PubMed ID: 
25344692

Spastic Paraplegia 46

Clinical Characteristics
Ocular Features: 

Congenital cataracts (not further described) have been reported in several individuals with this type of complicated spastic paraplegia.  Optic atrophy and nystagmus have not been reported.

Systemic Features: 

Stiffness and weakness of the lower limbs begins between 2 and 20 years of age.  This is slowly progressive although most individuals are still mobile with mild to moderate handicaps into the 4th decade.  The gait is spastic with weakness, hyperreflexia, and extensor plantar responses in the lower limbs.  The upper limbs are variably involved and movements are dysmetric.  Dysarthria and bladder dysfunction are often present.  Cerebellar ataxia is common and some patients first present with this as a prominent sign in the first and second decades.  Early cognitive development is normal but mild cognitive decline appears eventually.  Pes cavus and scoliosis may occur.

Brain imaging can show thinning of the corpus callosum, with mild cerebellar and cerebral atrophy.

Genetics

Linkage analysis identified a locus at 9p13.3 and sequencing confirmed homozygous or compound heterozygous mutations in GBA2.  The presence of parental consanguinity in some families supports autosomal recessive inheritance.

This database contains two other types of autosomal spastic paraplegia with ocular signs: spastic paraplegia 15 (270700) with a "flecked retina", and spastic paraplegia 7 (607259) with optic atrophy and nystagmus.  Cataracts have not been reported in these two conditions.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment is known for the neurological deficits but cataract surgery may be beneficial for visually significant cataracts.

References
Article Title: 

Mutations in GBA2 cause autosomal-recessive cerebellar ataxia with spasticity

Hammer MB, Eleuch-Fayache G, Schottlaender LV, Nehdi H, Gibbs JR, Arepalli SK, Chong SB, Hernandez DG, Sailer A, Liu G, Mistry PK, Cai H, Shrader G, Sassi C, Bouhlal Y, Houlden H, Hentati F, Amouri R, Singleton AB. Mutations in GBA2 cause autosomal-recessive cerebellar ataxia with spasticity. Am J Hum Genet. 2013 Feb 7;92(2):245-51. PubMed PMID: 23332917.

PubMed ID: 
23332917

Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia

Martin E, Sch?ole R, Smets K, Rastetter A, Boukhris A, Loureiro JL, Gonzalez MA, Mundwiller E, Deconinck T, Wessner M, Jornea L, Oteyza AC, Durr A, Martin JJ, Schols L, Mhiri C, Lamari F, Z?ochner S, De Jonghe P, Kabashi E, Brice A, Stevanin G. Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia. Am J Hum Genet. 2013 Feb 7;92(2):238-44. PubMed PMID: 23332916.

PubMed ID: 
23332916

A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum

Boukhris A, Feki I, Elleuch N, Miladi MI, Boland-Aug?(c) A, Truchetto J, Mundwiller E, Jezequel N, Zelenika D, Mhiri C, Brice A, Stevanin G. A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum. Neurogenetics. 2010 Oct;11(4):441-8.

PubMed ID: 
20593214

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

Gaze Palsy, Familial Horizontal, with Progressive Scoliosis 1

Clinical Characteristics
Ocular Features: 

Horizontal ophthalmoplegia is the ocular hallmark of this condition.  It is often present at birth with complete lack of horizontal gaze but in other individuals develops sometime in the first decade of life.  Horizontal smooth pursuit, saccades, optokinetic nystagmus, and vestibuloocular responses are lacking.  Vertical pursuit movements are usually intact except for smooth pursuit which is often saccadic.  Pendular nystagmus (usually horizontal) may be present and head shaking accompanies the nystagmus in some patients.  Many patients are orthophoric but some have a mild esotropia and/or vertical deviation.  The degree of convergence is variable.  Amblyopia does not usually occur and vision has been described as normal or near normal in spite of the presence of nystagmus.  Fusion and some degree of stereoacuity are generally present.  Compensatory head motion can effectively mask the horizontal palsy.  The ophthalmoplegia is progressive according to descriptions of some patients.

Some individuals are considered to have Duane retraction syndrome or congenital esotropia before the scoliosis becomes apparent.

Systemic Features: 

Progressive thoracolumbar scoliosis begins early in the first decade of life and may be evident by 2 years of life.  MRI reveals hypoplasia of the pons and cerebellar peduncles and electrophysiology studies provides evidence of abnormal (uncrossed) corticospinal and dorsal column-medial lemniscus pathways.  Cranial nerves VI and III seem to be intact.

Neuroimaging in some patients reveals medullary and pontine atrophy with hypoplasia of facial colliculi.

Genetics

Homozygous mutations in the ROBO3 gene (11q24.2) are responsible for this autosomal recessive disorder.  The ROBO3 protein product is important for normal midline axon crossing in the brainstem. Consanguinity is common among parents.

see Gaze Palsy, Familial Horizontal, with Progressive Scoliosis 2 (617542) for another condition with somewhat similar features.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Scoliosis may require surgical stabilization.  Physical therapy can be beneficial.

References
Article Title: 

Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis

Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, R?ob U, Shattuck D, Salamon G, Kudo LC, Ou J, Lin DD, Salih MA, Kansu T, Al Dhalaan H, Al Zayed Z, MacDonald DB, Stigsby B, Plaitakis A, Dretakis EK, Gottlob I, Pieh C, Traboulsi EI, Wang Q, Wang L, Andrews C, Yamada K, Demer JL, Karim S, Alger JR, Geschwind DH, Deller T, Sicotte NL, Nelson SF, Baloh RW, Engle EC. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science. 2004 Jun 4;304(5676):1509-13.

PubMed ID: 
15105459

Friedreich Ataxia 1

Clinical Characteristics
Ocular Features: 

Nystagmus and optic atrophy are important ocular signs.  The visual pathway, both anterior and posterior, is consistently involved and field defects are common even though many patients are asymptomatic.  OCT usually shows a reduced nerve fiber layer secondary to loss of axons.  About half of patients have abnormal visual evoked potentials.  A few patients experience a sudden loss of central vision during the second decade of life.

Systemic Features: 

Friedreich ataxia is a progressive neurodegenerative disorder with onset before puberty.  The spinocerebellar tracts, dorsal columns, pyramidal tracts, cerebellum, medulla, and optic radiation, may all be involved.  The outstanding symptom is ataxia with impairment of gait and weakness in the limbs.  Muscle weakness, extensor plantar responses, and absent lower limb reflexes are usually present.  Dysarthria is usually notable.  Sensory signs include impairment of position and vibratory senses.  'Twitching' in limbs and digits is often noted and 'restless leg syndrome' is common.

Secondary changes include pes cavus, scoliosis, and hammer toe.  Cardiac disease is frequently present and heart failure is the most common cause of death.  Most patients have hypertrophic cardiomyopathy with characteristic EKG changes and some have subaortic stenosis as part of the hypertrophied myocardium.  Diabetes mellitus is present in 20-25%.  Some hearing loss occurs in more than 10% of individuals.

Most patients require a wheelchair within 15 years of disease onset and the mean age of death is about 36 years.

Rare patients with a later onset of FRDA retain lower limb deep tendon reflexes.

Genetics

Homozygous mutations in FXN (9p21.11) are responsible for Friedreich ataxia.  The most common DNA abnormality is a GAA trinucleotide repeat expansion in intron 1.  The number of repeats in patients is 70 to more than 1000 compared with 5-30 in normal individuals.  FXN encodes the mitochondrial protein frataxin.

About 2% of individuals have point mutations in FXN instead of trinucleotide repeats.

Some of the phenotypic variations may be explained by differences in the number of GAA repeats.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Treatment is largely directed at symptoms including speech and physical therapy and mobility assistive devices. Scoliosis may require surgical intervention.

References
Article Title: 

Visual system involvement in patients with Friedreich's ataxia

Fortuna F, Barboni P, Liguori R, Valentino ML, Savini G, Gellera C, Mariotti C, Rizzo G, Tonon C, Manners D, Lodi R, Sadun AA, Carelli V. Visual system involvement in patients with Friedreich's ataxia. Brain. 2009 Jan;132(Pt 1):116-23.

PubMed ID: 
18931386

Friedreich ataxia: an overview

Delatycki MB, Williamson R, Forrest SM. Friedreich ataxia: an overview. J Med Genet. 2000 Jan;37(1):1-8. Review.

PubMed ID: 
10633128

Retinitis Pigmentosa and Mental Retardation

Clinical Characteristics
Ocular Features: 

The lenses may have pleomorphic white axial opacities but in other patients can be totally opacified.  Optic atrophy is present and vision may be reduced to light perception but nystagmus is absent.  Evidence suggests that vision loss is progressive.  Some patients have extensive posterior synechiae while others have been noted to have sluggish pupils.  High myopia is a feature. The retinal pigmentation has a typical retinitis pigmentosa picture with attenuated retinal vessels and equatorial bone spicule pigmentation located in the midperiphery while the macula can have a bull’s eye appearance.   

Systemic Features: 

Early development may seem normal but developmental milestones are usually delayed.  Postnatal microcephaly and growth deficiency with mental retardation and early hypotonia are typical features.  The mental retardation may be severe.  Scoliosis and arachnodactyly have been noted and hypogonadism has been reported.  Speech may not develop and mobility is sometimes limited.

Genetics

The family pattern suggests autosomal recessive inheritance.  Homozygosity mapping has identified in a region of chromosome 8 (8q21.2-22.1) that overlaps the region for Cohen syndrome () but no specific mutated gene has been identified.      

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

None.

References
Article Title: 

Retinitis Pigmentosa with Ataxia

Clinical Characteristics
Ocular Features: 

Pigmentary retinopathy has been noted by 6 months of age. Typical symptoms of retinitis pigmentosa are reported by early childhood.  The visual fields are progressively constricted and a ring scotoma can be plotted.  Night blindness and visual acuity loss are evident in the first decade of life and progressively worsen leading to severe handicaps by the third.  Fundus pigmentation in the midperiphery becomes more prominent and in at least some patients the pattern consists of typical bone spicules.  Cellophane maculopathy has been described.

Systemic Features: 

Proprioceptive deficits and areflexia appear in early childhood and ataxia worsens as individuals mature.  Scoliosis and general weakness and wasting become prominent manifestations.  Sensory neuropathy with loss of vibratory and position sense, astereognosia, and agraphesthesia can become apparent in the first decade of life.  Walking is delayed and gait abnormalities are clearly evident by the second decade leading to orthopedic deformities such as scoliosis.  Unassisted walking becomes impossible.  The intrinsic hand and foot muscles also have mild weakness.  Sural nerve biopsy may reveal loss of large myelinated fibers.  Hyperintense signals in the posterior spinal columns can be seen on MRI.  No anatomic changes have been described in the cerebrum or cerebellum.

Genetics

This is an autosomal recessive disorder resulting from homozygous mutations in FLVCR1 (1q32.2-q41).  This disorder has some clinical similarities to Biemond 1 syndrome but differs in the inheritance pattern and the molecular basis.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No specific treatment is available but physical therapy and low vision aids may improve the quality of life.

References
Article Title: 

Multiple Endocrine Neoplasia, Type IIB

Clinical Characteristics
Ocular Features: 

Corneal nerves are medullated and appear prominent.  Neuromas of the lid margins and sometimes the conjunctiva are common features.  Thickening of the entire eyelids may be present.

Systemic Features: 

Some manifestations may be seen in early childhood.  Prominent physical features include full lips, thickened eyelids, high arched palate and a marfanoid habitus.  Medullary carcinoma of the thyroid is almost always present and can be the cause of death in relatively young individuals. Metastases are usually to the regional lymph nodes or to liver, lungs, or bone. Pheochromocytomas and megacolon secondary to gastrointestinal neuromas are commonly seen.  The esophagus sometimes lacks normal motility for the same reason.  Neuromas often lead to thickening of the lips and tongue and can also appear as pedunculated nodules on these structures.  Cafe-au-lait spots and increased pigmentation of the hands, feet, and circumoral areas are frequently present.  Many patients have dysmorphic features suggestive of Marfan syndrome including a typical habitus, pectus excavatum, scoliosis, and pes cavus. Proximal myopathy and peripheral neuropathy are sometimes seen.

Another form of multiple endocrine neoplasia, called MEN2A, differs in the absence of mucosal neuromas and the marfanoid habitus.  MEN2A patients are more likely to have parathyroid hyperplasia.

Genetics

This is an autosomal dominant disorder caused by mutations in the tyrosine kinase domain of the RET gene (10q11.2). This disorder (MEN2B) may be allelic to MEN2A.  Perhaps half of MEN2B cases occur sporadically and in these the mutant RET allele is usually of paternal origin.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Treatment of local lesions is sometimes indicated.  Biochemical testing for pheochromocytoma should be done before any surgery.

References
Article Title: 

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