hydrolethalus syndrome 1

Hydrolethalus syndrome 1 (HLS1) is a rare and severe genetic disorder that affects fetal development, leading to multiple birth defects.

Characteristics of HLS1:

• Hydrocephaly: an accumulation of fluid in the brain, causing it to enlarge
• Absent upper midline structures of the brain: a rare condition where the upper part of the brain is missing or severely underdeveloped
• Micrognathia: a small lower jawbone
• Polydactyly: extra fingers or toes

Other possible features:

• Cleft lip or palate
• Club feet
• Anomalies of the ears, eyes, and nose
• Keyhole-shaped defect in the occipital bone (back of the skull)
• Abnormal genitalia
• Congenital heart and respiratory defects

HLS1 is an autosomal recessive lethal malformation syndrome, meaning that it is caused by a mutation in both copies of the HYLS1 gene and can be fatal if not detected and managed during fetal development.

References:

[1] (Context 10) - Hydrolethalus-1 (HLS1) is an autosomal recessive lethal malformation syndrome characterized by hydrocephaly with absent upper midline structures of the brain, micrognathia, and polydactyly. [2] (Context 4) - HLS is associated with HYLS1 mutations. The gene encoding HYLS1 is responsible for proper cilial development within the human body. [3] (Context 6) - Hydrolethalus syndrome 1 is an autosomal recessive lethal malformation syndrome characterized by hydrocephaly, absent upper midline brain structures, micrognathia, and polydactyly.

Common Signs and Symptoms of Hydrolethalus Syndrome 1

Hydrolethalus syndrome 1 (HLS1) is a rare genetic disorder that affects fetal development, resulting in severe birth defects. The signs and symptoms of HLS1 can vary, but some common features include:

• Craniofacial dysmorphic features: Micrognathia (small lower jaw), retrognathia (small upper jaw), cleft lip/palate, poorly formed nose, posteriorly rotated ears, and deep-set eyes [2][3]
• Abnormality of head or neck: Bifid nose
• Abnormality of limbs: Clubfoot
• Abnormality of prenatal development or birth: Polyhydramnios (excess amniotic fluid)
• Other features: Cleft lip or palate, club feet, anomalies of the ears, eyes, and nose, keyhole-shaped defect in the occipital bone, abnormal genitalia [4][5]

These symptoms can appear during pregnancy and as a newborn. It's essential to note that HLS1 is a severe fetal malformation syndrome characterized by craniofacial dysmorphic features, central nervous system, cardiac, respiratory tract, and limb abnormalities [10].

In most cases, the pregnancy is terminated after prenatal diagnosis due to the severity of the symptoms [8]. However, in some reported cases, additional features such as absent midline structures of the brain, congenital heart defect, and polydactyly have been observed [9][11].

It's crucial to understand that HLS1 affects fetal development in the womb and is a syndrome of infants only, with no reported cases of survival into childhood or adulthood [13].

Hydrolethalus syndrome 1 (HLS1) is a severe fetal malformation syndrome that requires prompt and accurate diagnosis to provide appropriate care and management for affected individuals.

Available Diagnostic Tests:

• Mutation scanning/screening and sequence analysis of selected exons: This test involves analyzing specific regions of the HYLS1 gene to identify mutations associated with HLS1. [5][8]
• Sanger sequencing (1): This is a type of DNA sequencing that can be used to confirm the presence of mutations in the HYLS1 gene. [5][8]
• Clinical Molecular Genetics test: This comprehensive test involves analyzing the entire coding region of the HYLS1 gene using bi-directional Sanger sequence analysis. [12]

Other Relevant Information:

• HLS1 can be distinguished from Meckel syndrome by analyzing kidney function, which is dysfunctional in Meckel syndrome due to cyst formation. [6]
• Abnormalities associated with HLS1 include hydrocephaly, absent upper midline brain structures, micrognathia, polydactyly, cleft lip or palate, club feet, ear, eye, and nose anomalies, a keyhole-shaped defect in the occipital bone, abnormal genitalia, and extra fluid surrounding the brain (hydrocephalus). [2][3][4]

Clinical Resources:

• Clinical Genetic Test offered by Bioarray for conditions (1): Hydrolethalus syndrome 1; Testing genes (1): HYLS1 (11q24.2) [5]
• Information about HLS1 and its clinical features, 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 can be found on various online platforms. [10]

Please note that these diagnostic tests may not be exhaustive, and it is essential to consult with a qualified healthcare professional for accurate diagnosis and management of HLS1.

Unfortunately, there are no specific drug treatments available for Hydrolethalus Syndrome 1 (HLS1). According to the search results, there is no treatment for HLS1, and it is considered a lethal malformation syndrome with a severe prognosis.

However, I can provide some information on the management and treatment of HLS1. While there are no specific drugs or treatments available, genetic counseling is recommended for affected families to discuss the 25% recurrence risk after an affected pregnancy [13].

It's also worth noting that HLS1 is often associated with other severe fetal malformations, such as hydrocephaly, absent midline structures of the brain, micrognathia, and polydactyly. In these cases, prenatal diagnosis may be possible through ultrasound or genetic testing.

Unfortunately, the prognosis for individuals with HLS1 is generally poor, with stillbirth or neonatal death being the rule [13]. However, rare cases of survival have been reported in some instances.

References: [13] - Management and treatment There is no treatment for HLS. Prognosis Stillbirth or neonatal death is the rule, although rare cases with several months survival have been reported. [15] - Hydrolethalus-1 (HLS1) is an autosomal recessive lethal malformation syndrome characterized by hydrocephaly with absent upper midline structures of the brain, micrognathia, and polydactyly. Various other features such as cleft lip or palate, club feet, anomalies of the ears, eyes...

Differential Diagnosis of Hydrolethalus Syndrome 1

Hydrolethalus syndrome 1 (HLS1) is a rare and severe genetic disorder characterized by hydrocephaly, absent upper midline brain structures, micrognathia, and polydactyly. When diagnosing HLS1, it's essential to consider other midline malformation syndromes that may present similar symptoms.

Other Midline Malformation Syndromes:

• Pallister-Hall Syndrome: A rare genetic disorder characterized by craniofacial dysmorphic features, central nervous system abnormalities, and limb anomalies.
• Smith-Lemli-Opitz Syndrome: A metabolic disorder that affects the development of multiple organs and systems, including the brain, heart, and limbs.
• Pseudo-trisomy 13: A rare genetic condition characterized by craniofacial dysmorphic features, central nervous system abnormalities, and limb anomalies.

Key Features to Consider:

When differentiating HLS1 from other midline malformation syndromes, the following key features should be considered:

• Hydrocephaly: The presence of hydrocephaly is a distinctive feature of HLS1.
• Absent upper midline brain structures: This characteristic is unique to HLS1 and can help differentiate it from other midline malformation syndromes.
• Micrognathia: Micrognathia, or a small lower jaw, is a common feature in HLS1.

Differential Diagnosis:

To accurately diagnose HLS1, clinicians should consider the following differential diagnosis:

• Meckel Syndrome: A rare genetic disorder characterized by craniofacial dysmorphic features, central nervous system abnormalities, and limb anomalies.
• Other midline malformation syndromes: Such as Pallister-Hall Syndrome, Smith-Lemli-Opitz Syndrome, and Pseudo-trisomy 13.

Genetic Testing:

Genetic testing can help confirm the diagnosis of HLS1. A missense mutation in the HYLS1 gene has been identified as the causative genetic alteration for HLS1.

References:

• Kopra O et al. (2005). Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1. Hum Mol Genet, 14(11), 1475-88.
• Chan BC, Shek TW, Lee CP. First-trimester diagnosis of hydrolethalus syndrome: A case report and review of the literature. Am J Med Genet, 2007;146A(2), 245-50.

By considering these key features and differential diagnoses, clinicians can accurately diagnose HLS1 and provide appropriate management and support for affected individuals and their families.