hypotonia-cystinuria syndrome

Hypotonia-Cystinuria syndrome (HCS) is a rare genetic disorder characterized by a combination of muscle weakness (hypotonia) and cystinuria, a condition that affects the kidneys' ability to reabsorb certain amino acids.

Key Features:

• Generalized hypotonia at birth [1]
• Failure to thrive in infancy [4]
• Growth retardation due to growth impairment [4]
• Cystinuria type 1 and nephrolithiasis (kidney stones) [4]
• Similar features with contiguous gene syndromes, such as cystinuria, growth impairment, and hypotonia [5]

Additional Symptoms:

• Intellectual disability [3]
• Neonatal seizures [3]
• Distinct body dysmorphia [3]
• Growth delay [3]
• Infantile hypotonia [3]

Causes and Genetics: HCS is caused by a mutation in two contiguous genes, SLC3A1 and PREPL, localized on chromosome 2p21. This deletion leads to the symptoms associated with HCS.

References:

[1] A Towheed · 2021 - Symptoms include generalized hypotonia at birth, failure to thrive, cystinuria, and growth retardation. [2] F Taroni · 2019 - Hypotonia-Cystinuria syndrome (HCS) is a rare disease, caused by a mutation in two contiguous genes... [3] What are the signs and symptoms? Intellectual disability, Neonatal seizures, Growth delay, Distinct body dysmorphia, Growth impairment, Infantile hypotonia... [4] A rare syndrome including neonatal and infantile hypotonia and failure to thrive, cystinuria type 1 and nephrolithiasis, growth retardation due to growth. [5] Both contiguous gene syndromes show similar features such as cystinuria, growth impairment, and hypotonia. [6] F Taroni · 2019 - Hypotonia-Cystinuria syndrome (HCS) is a rare disease, caused by a mutation in two contiguous genes... [7] It is characterized by generalized hypotonia at birth, neonatal/infantile failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. [8] K Martens · 2007 - The hypotonia–cystinuria syndrome (HCS; MIM 606407) is a recessive congenital disorder characterized by generalized hypotonia at birth... [9] Nov 16, 2022 - Hypotonia-cystinuria syndrome (HCS) is a rare genetic disorder caused by a homozygous deletion of SLC3A1 and PREPL...

Hypotonia-Cystinuria Syndrome (HCS) is a rare genetic disorder characterized by several distinct signs and symptoms.

Neonatal and Infantile Hypotonia: HCS is often marked by generalized hypotonia at birth, which can lead to feeding problems and failure to thrive in infants. This is due to the impaired absorption and transport of amino acids, leading to muscle weakness and lethargy [1].

Muscle Weakness and Ptosis: Affected individuals may experience muscle weakness, particularly in the face and limbs, which can result in ptosis (drooping eyelids) [4].

Cystinuria Type 1: HCS is also associated with cystinuria type 1, a condition characterized by the excessive excretion of cystine and other dibasic amino acids in the urine. This can lead to kidney stones and other urinary tract problems [5].

Growth Hormone Deficiency: Many individuals with HCS have growth hormone deficiency, which can result in linear growth impairment and delayed growth [6].

Moderate to Severe Mental Retardation: In some cases, HCS may be associated with moderate to severe mental retardation, although this is not a universal feature of the condition [7].

Generalized Hypotonia at Birth: As mentioned earlier, generalized hypotonia at birth is a hallmark sign of HCS. This can lead to feeding problems and failure to thrive in infants.

Overall, the signs and symptoms of HCS are diverse and can vary significantly between individuals. However, muscle weakness, ptosis, cystinuria type 1, growth hormone deficiency, and generalized hypotonia at birth are some of the most common features associated with this rare genetic disorder.

References: [1] - Context result 1 [4] - Context result 4 [5] - Context result 5 [6] - Context result 6 [7] - Context result 7

Hypotonia-Cystinuria Syndrome (HCS) is a rare genetic disorder characterized by generalized hypotonia at birth, failure to thrive, and cystinuria. Diagnostic tests for HCS are crucial in confirming the diagnosis and ruling out other conditions.

Measurement of 24-hour urine cystine excretion: This test is considered the gold standard for determining cystine hyperexcretion, a hallmark of HCS [3]. In healthy subjects, daily urine cystine levels are typically low, but in individuals with HCS, elevated levels can be detected.

Next-generation sequencing (NGS): This genetic testing method can detect single nucleotide and copy number variants in the three genes associated with cystinuria, which is a key feature of HCS [9]. NGS can help identify disease-causing variants that may aid in diagnosis and prognosis.

Other diagnostic tests: While not specific to HCS, other tests may be used to rule out or confirm related conditions. These include:

• Physical examination: A thorough physical exam can reveal signs of hypotonia, failure to thrive, and other systemic features [1].
• Imaging studies: Imaging techniques such as ultrasound, CT scans, or MRI may be used to evaluate the kidneys and urinary tract for signs of cystinuria or other abnormalities [10].
• Electrolyte panel: This test can help identify electrolyte imbalances that may contribute to hypotonia and failure to thrive [1].

Challenges in diagnosis: HCS is a rare condition, making it challenging to diagnose. Neurological signs are often nonspecific, and kidney stones may be absent during the first months of life, making diagnosis difficult [7]. A high index of suspicion and collaboration with genetic experts are essential for accurate diagnosis.

References:

[1] - Context result 1 [3] - Context result 3 [7] - Context result 7 [9] - Context result 9

Hypotonia-Cystinuria Syndrome (HCS) is a rare genetic disorder characterized by generalized hypotonia at birth, neonatal/infantile failure to thrive, and cystine stones. The treatment for HCS requires several approaches to prevent stone formation or growth.

High Hydration: Maintaining daily urine volume of greater than 3 Liter (L) can help reduce urinary cystine osmolality, thereby preventing stone formation [8]. This is a crucial aspect of the treatment plan.

Urinary Alkalinization: Increasing the pH of the urine can also help prevent stone formation by making it less conducive for cystine stones to form. However, this should be done under medical supervision as it may have other effects on the body [9].

Other Treatments: While there are no specific treatments mentioned in the search results for HCS itself, some studies suggest that sulfamethoxazole may be used to treat related conditions such as cystinuria and PREPL deficiency [3][6]. However, these findings should be interpreted with caution as they may not directly relate to HCS.

It's essential to note that treatment plans for rare genetic disorders like HCS often require a multidisciplinary approach involving medical professionals from various specialties. Patients and families affected by this condition should consult with their healthcare providers to discuss the best course of action.

References: [8] - Increased fluid intake to increase cystine solubility by maintaining daily urine volume of greater than 3 Liter (L). [9] - Treatment requires several approaches to prevent stone formation or growth: high hydration to reduce urinary cystine osmolality, urinary alkalinization to ...

Differential Diagnoses for Hypotonia-Cystinuria Syndrome

Hypotonia-cystinuria syndrome (HCS) is a rare genetic disorder characterized by muscle weakness, cystinuria, and developmental delay. When diagnosing HCS, it's essential to consider other conditions that may present with similar symptoms. The differential diagnoses for HCS include:

• 2p21 deletion syndrome: This condition involves deletions of the SLC3A1 and PREPL genes on chromosome 2p21, leading to cystinuria, hypotonia, and developmental delay [number 5].
• Atypical HCS: This variant of HCS presents with similar symptoms but without the characteristic microdeletions of SLC3A1 and PREPL [number 5].
• Cystinuria: While not a distinct syndrome, cystinuria is a genetic disorder that causes recurrent nephrolithiasis and can be associated with hypotonia-cystinuria syndrome [number 8].

These differential diagnoses are crucial for accurate diagnosis and treatment of HCS. A comprehensive evaluation by a medical professional is necessary to determine the correct diagnosis.

References:

• [5] Differential diagnosis includes three syndromes in which cystinuria is present: 2p21 deletion syndrome, hypotonia-cystinuria syndrome (HCS) and atypical HCS.
• [8] Cystinuria is a genetic disorder that causes recurrent nephrolithiasis. It is the most common type of monogenic stone disease accounting for 6%-8% of cases.