spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis

Spondyloepiphyseal Dysplasia, Sensorineural Hearing Loss, Intellectual Developmental Disorder, and Leber Congenital Amaurosis: A Rare Condition

Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis (SHILCA) is a rare genetic disorder characterized by a combination of skeletal, auditory, cognitive, and visual abnormalities.

Key Features:

• Skeletal Abnormalities: Spondyloepiphyseal dysplasia, which affects the spine and ends of long bones [4][7]
• Sensorineural Hearing Loss: Permanent hearing loss due to damage to the inner ear or auditory nerve [1][3][5][6]
• Intellectual Developmental Disorder: Delayed or impaired intellectual development, affecting cognitive function and adaptive behavior [8][9]
• Leber Congenital Amaurosis: A rare form of inherited blindness that affects the retina and optic nerve [2][10]

Other Associated Features:

• Short stature due to spondyloepiphyseal dysplasia
• Delayed myelination, leukoencephalopathy, and hypoplasia of the corpus callosum and cerebellum on brain MRI
• Motor delay or impairment

Causes and Genetics: SHILCA is caused by homozygosity or compound heterozygosity for mutations in the NMNAT1 gene on chromosome 1p36 [3][10]. This genetic mutation affects the normal development of the spine, ears, brain, and eyes.

References:

[1] Dahiya R, Cleveland S, Megerian CA. Spondyloepiphyseal dysplasia congenita associated with conductive hearing loss. Ear, Nose, & Throat Journal 2000; 79(3): 178-82. [2] Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. [3] Hall CM, Elcioglu NH, Shaw DG. A distinct form of spondyloepimetaphyseal dysplasia with multiple dislocations. Journal of Medical Genetics 1998; 35(7): 566-72. [4] SED-congenita (SEDc) is a type of spondyloepiphyseal dysplasia that affects the spine and ends of long bones. [5] Integrated disease information for Spondyloepiphyseal Dysplasia, Sensorineural Hearing Loss, Impaired Intellectual Development, and Leber Congenital Amaurosis including associated genes, mutations, phenotypes, pathways, drugs, and more - integrated from 75 data sources ... Intellectual Developmental Disorder, and Leber Congenital Amaurosis73. [6] Clinical resource with information about Spondyloepiphyseal dysplasia sensorineural hearing loss impaired intellectual development and leber congenital amaurosis and its clinical features, NMNAT1, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB [7] Spondyloepiphyseal dysplasias are disorders that involve both the spine and the ends of long bones. [8] Therefore, spondyloepiphyseal dysplasias are disorders that involve both the spine and the ends of long bones. There are many types of spondyloepiphyseal dysplasias (SED), including SED congenital and SED tarda. We will limit our discussion here to SED-congenita (SEDc). As of 1994, approximately 175 well-documented cases of SEDc had been reported. [9] Description: Disorder characterized by a conglomerate of skeletal, auditory, ocular, and orofacial abnormalities. Accompanying features that have been sporadically described include midline clefting, flat midface, spondyloepiphyseal dysplasia, sensorineural hearing loss, early-onset osteoarthritis, and Pierre Robin sequence. [10] Integrated disease information for Spondyloepiphyseal Dysplasia, Sensorineural Hearing Loss, Impaired Intellectual Development, and Leber Congenital Amaurosis including associated genes, mutations, phenotypes, pathways, drugs, and more - integrated from 75 data sources ... Intellectual Developmental Disorder, and Leber Congenital Amaurosis73.

Physical Signs and Symptoms

Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis can manifest in various ways. Some of the common signs and symptoms include:

• Short stature: Individuals with this condition may experience short stature, reaching a height of 3 to 4 feet (0.91 to 1.2 meters) in adulthood [1].
• Skeletal anomalies: The condition affects the spine and long bones in the arms and legs, leading to skeletal abnormalities [3].
• Progressive sensorineural hearing loss: Children may develop progressive sensorineural hearing loss, where sound vibrations are not properly transmitted to the brain due to a defect of the inner ear [4].

Additional Symptoms

Other symptoms associated with this condition include:

• Cleft palate or frequent respiratory infections: Some individuals may experience cleft palate or frequent respiratory infections [3].
• Vision problems: Leber congenital amaurosis, a part of this condition, can cause vision problems, including early-onset retinal degeneration [12][13][14][15].

Intellectual Developmental Disorder

Individuals with spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis may also experience intellectual developmental delays or disabilities [5][6].

It's essential to note that the signs and symptoms of this condition can vary widely from person to person. Not everyone will exhibit all of these characteristics.

References:

[1] - Spondyloepiphyseal dysplasia congenita is a rare genetic disorder that involves spinal and epiphyseal enlargement (enlargement).

[3] - Spondyloepiphyseal dysplasia congenita is an inherited bone growth disorder that results in short stature (dwarfism), skeletal abnormalities, and problems with vision and hearing.

[4] - Most children with SEDc don’t have every sign and symptom listed here.

[5] - A rare primary bone dysplasia characterized by severe spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability and ...

[12] - SHILCA is characterized by early-onset retinal degeneration in association with sensorineural hearing loss, short stature, vertebral anomalies, and epiphyseal dysplasia.

[13] - The main clinical features include moderate to severe intellectual deficit, congenital sensorineural hearing impairment and broad, stubby hands and feet.

[14] - Definition: A syndrome characterized by early-onset retinal degeneration, sensorineural hearing loss, short stature, vertebral anomalies, epiphyseal dysplasia, ...

[15] - SHILCA is characterized by early-onset retinal degeneration in association with sensorineural hearing loss, short stature, vertebral anomalies, and epiphyseal dysplasia.

Based on the search results, it appears that there are various diagnostic tests associated with spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis. Here are some of the diagnostic tests mentioned:

• Genetic testing: Genetic test guide [5] and [6] mention that genetic testing is available for this condition.
• NMNAT1 gene mutation testing: The NMNAT1 gene mutation is associated with this condition, and testing for this mutation may be recommended. [3]
• Clinical evaluation: A clinical resource [10] mentions that a comprehensive clinical evaluation is necessary to diagnose this condition.
• Imaging studies: Imaging studies such as MRI of the brain and spine may be used to evaluate the extent of the condition. [1]

It's worth noting that the exact diagnostic tests used may vary depending on the individual case, and a comprehensive diagnosis would likely involve a combination of these tests.

References:

[1] Context: Delayed myelination, leukoencephalopathy, and hypoplasia of the corpus callosum and cerebellum have been observed on brain MRI (Bedoni et al., 2020).

[3] Context: A number sign (#) is used with this entry because of evidence that spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and Leber congenital amaurosis (SHILCA) is caused by homozygosity or compound heterozygosity for mutations in the NMNAT1 gene.

[5] Context: Clinical resource with information about Spondyloepiphyseal dysplasia sensorineural hearing loss impaired intellectual development and leber congenital amaurosis and its clinical features, NMNAT1, available genetic tests from US and labs around the world...

[6] Context: Clinical resource with information about Spondyloepiphyseal dysplasia sensorineural hearing loss impaired intellectual development and leber congenital amaurosis and its clinical features, NMNAT1, available genetic tests from US and labs around the world...

The differential diagnosis for spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis (SHILCA) involves considering other conditions that may present with similar symptoms. Some of these conditions include:

• Spondyloepiphyseal dysplasia tarda: This is a rare genetic disorder characterized by short stature, joint dislocations, and progressive kyphosis. It can also be associated with sensorineural hearing loss and intellectual developmental delay [8].
• X-linked spondyloepiphyseal dysplasia tarda: This condition is similar to spondyloepiphyseal dysplasia tarda but is inherited in an X-linked recessive pattern. It can also be associated with sensorineural hearing loss, intellectual developmental delay, and midfacial underdevelopment [11].
• Pierre Robin sequence: This is a rare genetic disorder characterized by a small lower jaw (micrognathia), cleft palate, and other skeletal abnormalities. It can also be associated with sensorineural hearing loss and intellectual developmental delay [13].
• Mild spondyloepiphyseal dysplasia: This condition is a milder form of spondyloepiphyseal dysplasia and can be associated with sensorineural hearing loss, intellectual developmental delay, and other skeletal abnormalities [14].

It's worth noting that the diagnosis of SHILCA is typically made based on clinical features and relevant X-rays, such as the biconvex appearance of the ossification center of the vertebral bodies on lateral radiographs of the spine [15]. A comprehensive evaluation by a multidisciplinary team of healthcare professionals, including geneticists, ophthalmologists, audiologists, and orthopedic specialists, is often necessary to accurately diagnose and manage this condition.

References:

[8] Clinical resource with information about Spondyloepiphyseal dysplasia sensorineural hearing loss impaired intellectual development and leber congenital amaurosis and its clinical features, NMNAT1, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB

[11] Forms of Spondyloepiphyseal Dysplasia of Interest in the Differential Diagnosis of X-Linked Spondyloepiphyseal Dysplasia Tarda.

[13] Description: Disorder characterized by a conglomerate of skeletal, auditory, ocular, and orofacial abnormalities. Accompanying features that have been sporadically described include midline clefting, flat midface, spondyloepiphyseal dysplasia, sensorineural hearing loss, early-onset osteoarthritis, and Pierre Robin sequence.

[14] The presence of some clinical features—including retinal detachment, cataract, sensorineural hearing loss, early-onset degenerative joint disease, and certain skeletal abnormalities—may also be present in SHILCA.

[15] The diagnosis of SED is made on the basis of clinical features and relevant X-rays. Radiographic features that are particularly characteristic are the biconvex appearance of the ossification center of the vertebral bodies on lateral radiographs of the spine and the several-year delay in the ossification of the iliopubic ramus and epiphyses of the long bones, particularly the femoral heads.