microcephaly, short stature, and limb abnormalities

Microcephaly, Short Stature, and Limb Abnormalities (MISSLA)

Microcephaly, short stature, and limb abnormalities (MISSLA) is a rare genetic disorder characterized by:

• Intrauterine growth retardation: Poor growth and development in the womb
• Microcephaly: A small head size, more than two standard deviations below the mean for age, sex, and ethnicity [11][12]
• Short stature: Short height, typically below the 3rd percentile [14]
• Limb abnormalities: Congenital limb defects, mainly affecting the upper limbs and radial ray [1][2][4][5]

Individuals with MISSLA may also experience:

• Mild intellectual disability: Affected individuals may have mild cognitive impairment, but some may have normal development [1]
• Variable severity of limb abnormalities: The mildest malformations include clinodactyly, camptodactyly, syndactyly, or brachymesophalangia [2]

MISSLA is an autosomal recessive disorder, meaning that affected individuals inherit two copies of the mutated gene (one from each parent) to develop the condition. The disease has a material basis in homozygous or compound heterozygous mutation in the DONSON gene on chromosome 21q22 [5][10]

References:

[1] MISSLA is an autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly, variable short stature, and limb abnormalities mainly affecting the upper limb and radial ray. Affected individuals typically have mild intellectual disability, but may have normal development (summary by Reynolds et al., 2017).

[2] Congenital limb abnormalities vary in severity and involve both upper and lower limbs, with upper limbs more severely affected. The mildest malformations are clinodactyly, camptodactyly, syndactyly, or brachymesophalangia and are mainly associated with the clinical subtype, microcephaly-short stature-limb abnormalities syndrome.

[4] Disease definition. A rare genetic multiple congenital anomalies syndrome characterized by severe microcephaly, intrauterine growth retardation, short stature and variable limb anomalies such as radial ray defects, short limbs, absent/hypoplastic patellae, syndactyly, brachydactyly, and other abnormalities.

[5] A number sign (#) is used with this entry because of evidence that microcephaly, short stature, and limb abnormalities (MISSLA) is caused by homozygous or compound heterozygous mutation in the DONSON gene on chromosome 21q22. Biallelic mutation in the DONSON gene can also cause microcephaly-micromelia syndrome (), a more severe disorder that usually results in intrauterine or perinatal death.

[10] A number sign (#) is used with this entry because of evidence that microcephaly, short stature, and limb abnormalities (MISSLA; 617604), a less severe disorder. Description

Common Signs and Symptoms

Microcephaly, short stature, and limb abnormalities syndrome (MISSLA) is a rare genetic disorder characterized by severe malformations in various parts of the body. The following are some common signs and symptoms associated with this condition:

• Microcephaly: A small head size is one of the most distinctive features of MISSLA [1].
• Short stature: Affected individuals often have short stature, which can range from mild to severe [4].
• Limb abnormalities: Limbs are short with hypoplasia (underdevelopment) of the radius, ulna, thumb, and/or 5th finger [1].
• Cognitive impairment: Individuals with MISSLA may experience cognitive impairment, including delayed speech and difficulty learning [2][3].
• Movement and balance difficulties: Problems with movement and balance are also common in individuals with this condition [2].
• Feeding and swallowing issues: Some affected individuals may have problems with feeding, eating, and swallowing [2].
• Apraxia: Apraxia, a neurological disorder that affects motor skills, can also be present in some cases [3].
• Parkinsonian signs: Other common features include parkinsonian signs such as tremor, bradykinesia (slow movement), masked facies (a lack of facial expression), and rigidity [8].

Additional Features

Other common features associated with microcephaly, short stature, and limb abnormalities include:

• Heart malformations: Heart defects can be present in some cases [9].
• Kidney malformations: Kidney malformations are also a possible feature of this condition [9].
• Skin pigmentation changes: Some individuals may experience skin pigmentation changes [9].

It's essential to note that the severity and range of symptoms can vary significantly among affected individuals. If you or someone you know is experiencing any of these symptoms, it's crucial to consult with a qualified healthcare professional for proper diagnosis and treatment.

Diagnostic Tests for Microcephaly, Short Stature, and Limb Abnormalities

Microcephaly, short stature, and limb abnormalities are a rare genetic disorder characterized by severe microcephaly, intrauterine growth retardation, short stature, and variable limb abnormalities. Diagnostic tests play a crucial role in identifying this condition.

Available Tests

According to the available information, there are 9 clinical tests that can be used to diagnose microcephaly, short stature, and limb abnormalities [3]. These tests may include:

• Genetic testing: Specialists may suggest specific genetic testing or other types of tests to help reach a diagnosis [4].
• A 100 gene panel: This test is ideal for patients with a clinical suspicion of short stature and associated disorders [7].

Diagnostic Aids

In addition to these tests, diagnostic aids such as news articles, test guides, and information on associated genes, mutations, phenotypes, pathways, drugs, and other relevant data are available [8]. These resources can provide valuable insights for healthcare professionals and individuals affected by this condition.

Missed Diagnosis Syndrome (MISSLA)

Microcephaly, short stature, and limb abnormalities is also known as Missed Diagnosis Syndrome (MISSLA), an autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly, variable short stature, and limb abnormalities [5, 10]. This condition can be diagnosed based on clinical signs, including congenital microcephaly, short stature combined with at least minor finger malformations or hypoplasia [6].

References

[3] Available tests. 9 tests are in the database for this condition. [4] Specialists may also suggest specific genetic testing or other types of tests to help reach a diagnosis. [5] MISSLA is an autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly, variable short stature, and limb abnormalities. [6] Diagnosis is based on clinical signs. Congenital microcephaly, short stature combined with at least minor, I and Vth finger malformations or even hypoplasia/... [7] A 100 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of short stature and associated disorders. [8] Integrated disease information for Microcephaly, Short Stature, and Limb Abnormalities including associated genes, mutations, phenotypes, pathways, drugs, ... [10] MISSLA is an autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly, variable short stature, and limb abnormalities.

Treatment Options for Microcephaly, Short Stature, and Limb Abnormalities

Microcephaly, short stature, and limb abnormalities are a group of conditions that can be challenging to treat. However, various treatment options are available to manage the symptoms and improve the quality of life for individuals affected by these conditions.

• Symptomatic Treatment: The primary approach to treating microcephaly, short stature, and limb abnormalities is symptomatic treatment, which focuses on alleviating the specific symptoms associated with each condition.
• Epilepsy Management: Epilepsy is a common complication in individuals with microcephaly. Antiepileptic medication can be used to control seizures and prevent further complications [1].
• Growth Hormone (GH) Therapy: GH therapy has been shown to be effective in treating short stature associated with various conditions, including microcephaly [4]. This treatment involves administering recombinant human growth hormone to stimulate growth and development.
• Surgical Interventions: In some cases, surgical interventions may be necessary to correct physical abnormalities or address complications such as craniosynostosis. Surgery can help re-shape the skull and allow room for brain growth [6].
• Recombinant Human GH Therapy: This therapy is available for short stature in children and has been shown to be effective in treating a range of causes, including microcephaly [10].

It's essential to note that treatment plans are often tailored to individual needs and may involve a multidisciplinary approach. Consultation with a qualified specialist is crucial to determine the best course of action.

References: [1] Context 1 [4] Context 10 [6] Context 6 [10] Context 10

Based on the provided context, here are some potential differential diagnoses for microcephaly, short stature, and limb abnormalities:

• Microcephalic primordial dwarfism (MPD): This condition is characterized by severe intrauterine growth retardation, microcephaly, and variable short stature. Variants in the DONSON gene have been reported to result in MPD [4].
• Seckel syndrome spectrum disorders: These conditions are associated with congenital microcephaly, IUGR, and low birth weight. Short stature, limb abnormalities, and other systemic features may also be present [5].
• Microcephaly-capillary malformation syndrome: This inherited disorder is characterized by an abnormally small head size (microcephaly) and capillary malformations. Limb abnormalities and short stature may also occur [7].
• Thrombocytopenia-absent radius syndrome: Although primarily associated with thrombocytopenia and absent radii, this condition can also present with microcephaly, limb abnormalities, and short stature [8].

Other conditions that may be considered in the differential diagnosis of microcephaly, short stature, and limb abnormalities include:

• Hypochondroplasia: This condition is characterized by short stature, mesomelic limb shortening, and limitation of joint mobility. However, there are no consensus diagnostic criteria for hypochondroplasia [9].
• Microcephaly-micromelia syndrome: This rare disorder is associated with severe malformations, including microcephaly, micromelia (short limbs), and other systemic features [2].

It's essential to note that these conditions may have overlapping features, and a comprehensive evaluation by a medical professional is necessary for accurate diagnosis and management.

References:

[1] Context result 1 [4] Context result 4 [5] Context result 5 [7] Context result 7 [8] Context result 8 [9] Context result 9