Kilquist syndrome

Mendelian MONDO:0033664 Pathograph 10 hereditary disease syndromic hearing loss

Kilquist syndrome is an autosomal recessive multisystem disorder caused by biallelic loss-of-function variants in SLC12A2, which encodes the NKCC1 sodium-potassium-chloride cotransporter. Loss of NKCC1 disrupts ion transport in the cochlea, neurons, and secretory epithelia, producing profound sensorineural hearing loss, severe developmental delay, hypotonia, growth failure, gastrointestinal abnormalities, and marked impairment of saliva and other epithelial secretions.

1
Mappings
0
Definitions
1
Inheritance
9
Pathophysiology
0
Histopathology
5
Phenotypes
10
Pathograph
1
Genes
1
Treatments
0
Subtypes
2
Differentials
1
Datasets
0
Trials
0
Models
🔗

Mappings

MONDO
MONDO:0033664 Kilquist syndrome
skos:exactMatch MONDO
👪

Inheritance

1
Autosomal recessive inheritance HP:0000007
Kilquist syndrome is caused by biallelic loss of function of SLC12A2.
Autosomal recessive inheritance
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"Like other SLC12 gene family disorders, Kilquist syndrome is an autosomal recessive condition caused by the loss of function of SLC12A2."
This directly states the mode of inheritance and causal mechanism.
⚙

Pathophysiology

9
Biallelic SLC12A2 / NKCC1 deficiency
Kilquist syndrome is caused by biallelic pathogenic variants in SLC12A2, which encodes the NKCC1 cotransporter.
SLC12A2 link
monoatomic ion transmembrane transport link ⚠ ABNORMAL
Show evidence (2 references)
PMID:30740830 SUPPORT Human Clinical
"Next-generation sequencing revealed a uniparental isodisomy in chromosome 5, and a 22 kb homozygous deletion in SLC12A2, which encodes for sodium, potassium, and chloride transporter in the basolateral membrane of secretory epithelia."
This directly anchors the syndrome to a biallelic SLC12A2 lesion affecting the NKCC1 transporter.
PMID:30740830 SUPPORT Human Clinical
"Together with the described phenotype of the Slc12a2-knockout mouse model, our results suggest that the absence of functional SLC12A2 causes a new genetic syndrome and is crucial for the development of auditory, neurologic, and gastrointestinal tissues."
This directly links loss of functional SLC12A2 to the multisystem developmental phenotype.
Truncated or absent NKCC1 protein
Pathogenic splice variants produce truncated NKCC1 and impair dimerization or eliminate detectable transporter protein.
SLC12A2 link
Show evidence (3 references)
PMID:40678848 SUPPORT In Vitro
"The effect of this mutation was further investigated using exon-walking PCR and Sanger sequencing, which confirmed exon 23 skipping in the patient's mRNA, resulting in a truncated NKCC1 protein."
This directly supports RNA-level and protein-level disruption of NKCC1.
PMID:40678848 SUPPORT Computational
"In silico structural modeling suggested compromised dimerization stability"
This supports a computationally inferred structural mechanism in which mutant NKCC1 has impaired dimerization stability.
PMID:40678848 SUPPORT In Vitro
"immunoblotting analysis, revealing the absence of the dimeric form of NKCC1 in patient-derived peripheral blood mononuclear cells."
This provides cell-based support that the mutant transporter fails to form the normal dimeric state.
Cochlear endolymph secretion failure
NKCC1 deficiency disrupts the inner-ear fluid-secretion program required for normal auditory function and underlies profound hearing loss.
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"Together with the described phenotype of the Slc12a2-knockout mouse model, our results suggest that the absence of functional SLC12A2 causes a new genetic syndrome and is crucial for the development of auditory, neurologic, and gastrointestinal tissues."
This supports a distinct auditory-development branch downstream of NKCC1 loss.
Neuronal ion-homeostasis disruption
NKCC1 deficiency perturbs neuronal chloride transport and brain-development programs, contributing to severe developmental impairment and hypotonia.
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"Together with the described phenotype of the Slc12a2-knockout mouse model, our results suggest that the absence of functional SLC12A2 causes a new genetic syndrome and is crucial for the development of auditory, neurologic, and gastrointestinal tissues."
This supports a discrete neurologic-developmental branch downstream of NKCC1 deficiency.
Secretory epithelial fluid-secretion failure
Loss of NKCC1 compromises secretory epithelial function, producing marked salivary and other exocrine secretion defects with gastrointestinal and respiratory consequences.
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"Our case is the first known human presentation of complete loss of NKCC1 and demonstrates the role of SLC12A2 in human secretory systems and disease."
This directly supports a secretory-epithelial branch downstream of NKCC1 loss.
Profound sensorineural hearing impairment
Inner-ear dysfunction produces the hallmark profound bilateral sensorineural hearing loss of Kilquist syndrome.
Show evidence (1 reference)
PMID:40678848 SUPPORT Human Clinical
"This study presents the case of a child with multiple congenital anomalies, severe hypotonia, and profound bilateral sensorineural hearing loss."
This supports the phenotype-level auditory outcome downstream of cochlear NKCC1 dysfunction.
Severe neurodevelopmental impairment
Neuronal NKCC1 dysfunction contributes to global developmental delay and hypotonia.
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation."
This directly supports severe neurodevelopmental impairment as a downstream outcome in the human syndrome.
Xerostomia and epithelial secretion defects
Secretory failure produces profound impairment of salivary and other epithelial secretions.
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"This new syndrome is associated with a loss of function mutation in SLC12A2; we now refer to this novel disease as Kilquist syndrome, which is additionally characterized by the absence of saliva, tears, and sweat, mucus plugging and respiratory problems reminiscent of cystic fibrosis, and severe..."
This directly supports epithelial secretion failure as a distinct downstream branch of disease.
Gastrointestinal and respiratory complications
NKCC1-related secretory dysfunction contributes to severe gastrointestinal abnormalities and mucus-related respiratory disease.
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"In summary, we present a novel cause of syndromic hearing loss associated with global developmental delay, failure to thrive, respiratory problems, absent salivation and sweat production, and gastrointestinal abnormalities."
This directly supports downstream gastrointestinal and respiratory complications in the human syndrome.
⏥

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Kilquist syndrome Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Ear 1
Sensorineural hearing impairment Sensorineural hearing impairment (HP:0000407)
Show evidence (1 reference)
PMID:40678848 SUPPORT Human Clinical
"This study presents the case of a child with multiple congenital anomalies, severe hypotonia, and profound bilateral sensorineural hearing loss."
This directly supports profound sensorineural hearing loss as a core phenotype.
Head and Neck 1
Xerostomia Xerostomia (HP:0000217)
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"This new syndrome is associated with a loss of function mutation in SLC12A2; we now refer to this novel disease as Kilquist syndrome, which is additionally characterized by the absence of saliva, tears, and sweat, mucus plugging and respiratory problems reminiscent of cystic fibrosis, and severe..."
This directly supports severe salivary deficiency as a core phenotype.
Musculoskeletal 1
Hypotonia Hypotonia (HP:0001252)
Show evidence (1 reference)
PMID:40678848 SUPPORT Human Clinical
"This study presents the case of a child with multiple congenital anomalies, severe hypotonia, and profound bilateral sensorineural hearing loss."
This directly supports hypotonia as part of the phenotype.
Nervous System 1
Global developmental delay Global developmental delay (HP:0001263)
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation."
The original syndrome description directly identifies global developmental delay.
Growth 1
Failure to thrive Failure to thrive (HP:0001508)
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"In summary, we present a novel cause of syndromic hearing loss associated with global developmental delay, failure to thrive, respiratory problems, absent salivation and sweat production, and gastrointestinal abnormalities."
The syndrome summary explicitly includes failure to thrive.
🧬

Genetic Associations

1
SLC12A2 (Loss-of-function)
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"Like other SLC12 gene family disorders, Kilquist syndrome is an autosomal recessive condition caused by the loss of function of SLC12A2."
This directly supports the causal gene and variant mechanism.
💊

Treatments

1
Supportive multidisciplinary management
Action: supportive care MAXO:0000950
Management is supportive and may include hearing rehabilitation, nutritional support, airway and pulmonary management, and treatment of gastrointestinal complications.
Show evidence (1 reference)
PMID:30740830 PARTIAL Human Clinical
"Cochlear implants were placed although the parents not that he has functionally derived no benefit."
This provides partial support that management is currently symptomatic, including hearing-directed interventions.
🔀

Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from Kilquist syndrome:

Cystic fibrosis MONDO:0009061
Overlapping Features Kilquist syndrome can resemble cystic fibrosis because of mucus plugging, poor growth, and gastrointestinal symptoms, but it is distinguished by profound congenital hearing loss and biallelic SLC12A2 deficiency.
Distinguishing Features
  • Profound sensorineural hearing loss and absent salivation favor Kilquist syndrome.
  • Positive CFTR-associated testing and classic pancreatic-pulmonary phenotype favor cystic fibrosis.
Usher syndrome Not Yet Curated MONDO:0019501
Overlapping Features Usher syndrome overlaps with Kilquist syndrome through congenital hearing loss, but Kilquist syndrome is distinguished by severe gastrointestinal and secretory epithelial dysfunction rather than retinitis pigmentosa.
Distinguishing Features
  • Global developmental delay and absent epithelial secretions favor Kilquist syndrome.
  • Progressive retinopathy with deafblindness favors Usher syndrome.
📊

Related Datasets

1
Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2. PMID:30740830
Foundational human case-based dataset defining Kilquist syndrome through deep clinical phenotyping, genomic diagnosis, and fibroblast-based functional validation of complete NKCC1 loss.
human n=1
Conditions: Kilquist syndrome homozygous SLC12A2 deletion
PMID:30740830
Show evidence (1 reference)
PMID:30740830 SUPPORT Human Clinical
"Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation."
This supports the publication as the foundational disease-defining human phenotype dataset for Kilquist syndrome.
{ }

Source YAML

click to show 
name: Kilquist syndrome
creation_date: '2026-04-11T19:38:25Z'
updated_date: '2026-04-12T00:11:00Z'
category: Mendelian
description: >-
  Kilquist syndrome is an autosomal recessive multisystem disorder caused by
  biallelic loss-of-function variants in SLC12A2, which encodes the NKCC1
  sodium-potassium-chloride cotransporter. Loss of NKCC1 disrupts ion transport
  in the cochlea, neurons, and secretory epithelia, producing profound
  sensorineural hearing loss, severe developmental delay, hypotonia, growth
  failure, gastrointestinal abnormalities, and marked impairment of saliva and
  other epithelial secretions.
disease_term:
  preferred_term: Kilquist syndrome
  term:
    id: MONDO:0033664
    label: Kilquist syndrome
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0033664
      label: Kilquist syndrome
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
parents:
- hereditary disease
- syndromic hearing loss
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    Kilquist syndrome is caused by biallelic loss of function of SLC12A2.
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Like other SLC12 gene family disorders, Kilquist syndrome is an autosomal recessive condition caused by the loss of function of SLC12A2.
    explanation: >-
      This directly states the mode of inheritance and causal mechanism.
pathophysiology:
- name: Biallelic SLC12A2 / NKCC1 deficiency
  description: >-
    Kilquist syndrome is caused by biallelic pathogenic variants in SLC12A2,
    which encodes the NKCC1 cotransporter.
  genes:
  - preferred_term: SLC12A2
    term:
      id: hgnc:10911
      label: SLC12A2
  biological_processes:
  - preferred_term: monoatomic ion transmembrane transport
    modifier: ABNORMAL
    term:
      id: GO:0034220
      label: monoatomic ion transmembrane transport
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Next-generation sequencing revealed a uniparental isodisomy in chromosome 5, and a 22 kb homozygous deletion in SLC12A2, which encodes for sodium, potassium, and chloride transporter in the basolateral membrane of secretory epithelia.
    explanation: >-
      This directly anchors the syndrome to a biallelic SLC12A2 lesion affecting
      the NKCC1 transporter.
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Together with the described phenotype of the Slc12a2-knockout mouse model, our results suggest that the absence of functional SLC12A2 causes a new genetic syndrome and is crucial for the development of auditory, neurologic, and gastrointestinal tissues.
    explanation: >-
      This directly links loss of functional SLC12A2 to the multisystem
      developmental phenotype.
  downstream:
  - target: Truncated or absent NKCC1 protein
    description: Biallelic pathogenic variants abolish normal NKCC1 protein production or stability
- name: Truncated or absent NKCC1 protein
  description: >-
    Pathogenic splice variants produce truncated NKCC1 and impair dimerization or
    eliminate detectable transporter protein.
  genes:
  - preferred_term: SLC12A2
    term:
      id: hgnc:10911
      label: SLC12A2
  evidence:
  - reference: PMID:40678848
    reference_title: "Identification and Characterization of a Novel Biallelic SLC12A2 Variant Associated With Kilquist Syndrome (OMIM #619080)."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The effect of this mutation was further investigated using exon-walking PCR and Sanger sequencing, which confirmed exon 23 skipping in the patient's mRNA, resulting in a truncated NKCC1 protein.
    explanation: >-
      This directly supports RNA-level and protein-level disruption of NKCC1.
  - reference: PMID:40678848
    reference_title: "Identification and Characterization of a Novel Biallelic SLC12A2 Variant Associated With Kilquist Syndrome (OMIM #619080)."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: In silico structural modeling suggested compromised dimerization stability
    explanation: >-
      This supports a computationally inferred structural mechanism in which
      mutant NKCC1 has impaired dimerization stability.
  - reference: PMID:40678848
    reference_title: "Identification and Characterization of a Novel Biallelic SLC12A2 Variant Associated With Kilquist Syndrome (OMIM #619080)."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      immunoblotting analysis, revealing the absence of the dimeric form of NKCC1 in patient-derived peripheral blood mononuclear cells.
    explanation: >-
      This provides cell-based support that the mutant transporter fails to form
      the normal dimeric state.
  downstream:
  - target: Cochlear endolymph secretion failure
    description: Loss of NKCC1 disrupts the inner-ear ion transport needed for hearing
  - target: Neuronal ion-homeostasis disruption
    description: Loss of NKCC1 perturbs neuronal chloride handling and early brain development
  - target: Secretory epithelial fluid-secretion failure
    description: Loss of NKCC1 compromises epithelial fluid secretion
- name: Cochlear endolymph secretion failure
  description: >-
    NKCC1 deficiency disrupts the inner-ear fluid-secretion program required for
    normal auditory function and underlies profound hearing loss.
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Together with the described phenotype of the Slc12a2-knockout mouse model, our results suggest that the absence of functional SLC12A2 causes a new genetic syndrome and is crucial for the development of auditory, neurologic, and gastrointestinal tissues.
    explanation: >-
      This supports a distinct auditory-development branch downstream of NKCC1
      loss.
  downstream:
  - target: Profound sensorineural hearing impairment
    description: Cochlear fluid-homeostasis failure produces the syndrome's hallmark deafness
- name: Neuronal ion-homeostasis disruption
  description: >-
    NKCC1 deficiency perturbs neuronal chloride transport and brain-development
    programs, contributing to severe developmental impairment and hypotonia.
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Together with the described phenotype of the Slc12a2-knockout mouse model, our results suggest that the absence of functional SLC12A2 causes a new genetic syndrome and is crucial for the development of auditory, neurologic, and gastrointestinal tissues.
    explanation: >-
      This supports a discrete neurologic-developmental branch downstream of
      NKCC1 deficiency.
  downstream:
  - target: Severe neurodevelopmental impairment
    description: Neuronal transport defects contribute to developmental delay and hypotonia
- name: Secretory epithelial fluid-secretion failure
  description: >-
    Loss of NKCC1 compromises secretory epithelial function, producing marked
    salivary and other exocrine secretion defects with gastrointestinal and
    respiratory consequences.
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our case is the first known human presentation of complete loss of NKCC1 and demonstrates the role of SLC12A2 in human secretory systems and disease.
    explanation: >-
      This directly supports a secretory-epithelial branch downstream of NKCC1
      loss.
  downstream:
  - target: Xerostomia and epithelial secretion defects
    description: Secretory failure causes absent salivation and related epithelial symptoms
  - target: Gastrointestinal and respiratory complications
    description: Secretory failure contributes to severe GI dysfunction and mucus-related respiratory problems
- name: Profound sensorineural hearing impairment
  description: >-
    Inner-ear dysfunction produces the hallmark profound bilateral sensorineural
    hearing loss of Kilquist syndrome.
  evidence:
  - reference: PMID:40678848
    reference_title: "Identification and Characterization of a Novel Biallelic SLC12A2 Variant Associated With Kilquist Syndrome (OMIM #619080)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This study presents the case of a child with multiple congenital anomalies, severe hypotonia, and profound bilateral sensorineural hearing loss.
    explanation: >-
      This supports the phenotype-level auditory outcome downstream of cochlear
      NKCC1 dysfunction.
- name: Severe neurodevelopmental impairment
  description: >-
    Neuronal NKCC1 dysfunction contributes to global developmental delay and
    hypotonia.
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation.
    explanation: >-
      This directly supports severe neurodevelopmental impairment as a downstream
      outcome in the human syndrome.
- name: Xerostomia and epithelial secretion defects
  description: >-
    Secretory failure produces profound impairment of salivary and other
    epithelial secretions.
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This new syndrome is associated with a loss of function mutation in SLC12A2; we now refer to this novel disease as Kilquist syndrome, which is additionally characterized by the absence of saliva, tears, and sweat, mucus plugging and respiratory problems reminiscent of cystic fibrosis, and severe gastrointestinal problems.
    explanation: >-
      This directly supports epithelial secretion failure as a distinct
      downstream branch of disease.
- name: Gastrointestinal and respiratory complications
  description: >-
    NKCC1-related secretory dysfunction contributes to severe gastrointestinal
    abnormalities and mucus-related respiratory disease.
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In summary, we present a novel cause of syndromic hearing loss associated with global developmental delay, failure to thrive, respiratory problems, absent salivation and sweat production, and gastrointestinal abnormalities.
    explanation: >-
      This directly supports downstream gastrointestinal and respiratory
      complications in the human syndrome.
phenotypes:
- name: Sensorineural hearing impairment
  category: Otolaryngologic
  description: >-
    Profound bilateral sensorineural hearing loss is the hallmark phenotype of
    Kilquist syndrome.
  phenotype_term:
    preferred_term: Sensorineural hearing impairment
    term:
      id: HP:0000407
      label: Sensorineural hearing impairment
  evidence:
  - reference: PMID:40678848
    reference_title: "Identification and Characterization of a Novel Biallelic SLC12A2 Variant Associated With Kilquist Syndrome (OMIM #619080)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This study presents the case of a child with multiple congenital anomalies, severe hypotonia, and profound bilateral sensorineural hearing loss.
    explanation: >-
      This directly supports profound sensorineural hearing loss as a core
      phenotype.
- name: Global developmental delay
  category: Neurologic
  description: >-
    Severe developmental impairment is part of the syndromic neurologic
    phenotype.
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation.
    explanation: >-
      The original syndrome description directly identifies global developmental
      delay.
- name: Hypotonia
  category: Neurologic
  description: >-
    Generalized hypotonia is a recurrent neurologic feature in Kilquist
    syndrome.
  phenotype_term:
    preferred_term: Hypotonia
    term:
      id: HP:0001252
      label: Hypotonia
  evidence:
  - reference: PMID:40678848
    reference_title: "Identification and Characterization of a Novel Biallelic SLC12A2 Variant Associated With Kilquist Syndrome (OMIM #619080)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This study presents the case of a child with multiple congenital anomalies, severe hypotonia, and profound bilateral sensorineural hearing loss.
    explanation: >-
      This directly supports hypotonia as part of the phenotype.
- name: Failure to thrive
  category: Growth
  description: >-
    Poor growth and nutritional failure reflect the syndrome's severe
    gastrointestinal and secretory dysfunction.
  phenotype_term:
    preferred_term: Failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In summary, we present a novel cause of syndromic hearing loss associated with global developmental delay, failure to thrive, respiratory problems, absent salivation and sweat production, and gastrointestinal abnormalities.
    explanation: >-
      The syndrome summary explicitly includes failure to thrive.
- name: Xerostomia
  category: Gastrointestinal
  description: >-
    Absent or severely reduced salivation is a hallmark secretory manifestation
    of Kilquist syndrome.
  phenotype_term:
    preferred_term: Xerostomia
    term:
      id: HP:0000217
      label: Xerostomia
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This new syndrome is associated with a loss of function mutation in SLC12A2; we now refer to this novel disease as Kilquist syndrome, which is additionally characterized by the absence of saliva, tears, and sweat, mucus plugging and respiratory problems reminiscent of cystic fibrosis, and severe gastrointestinal problems.
    explanation: >-
      This directly supports severe salivary deficiency as a core phenotype.
genetic:
- name: SLC12A2
  association: Loss-of-function
  gene_term:
    preferred_term: SLC12A2
    term:
      id: hgnc:10911
      label: SLC12A2
  notes: >-
    Kilquist syndrome is caused by biallelic loss of NKCC1 function due to
    deletion or splice-disrupting variants in SLC12A2.
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Like other SLC12 gene family disorders, Kilquist syndrome is an autosomal recessive condition caused by the loss of function of SLC12A2.
    explanation: >-
      This directly supports the causal gene and variant mechanism.
treatments:
- name: Supportive multidisciplinary management
  description: >-
    Management is supportive and may include hearing rehabilitation, nutritional
    support, airway and pulmonary management, and treatment of gastrointestinal
    complications.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cochlear implants were placed although the parents not that he has functionally derived no benefit.
    explanation: >-
      This provides partial support that management is currently symptomatic,
      including hearing-directed interventions.
differential_diagnoses:
- name: Cystic fibrosis
  disease_term:
    preferred_term: cystic fibrosis
    term:
      id: MONDO:0009061
      label: cystic fibrosis
  description: >-
    Kilquist syndrome can resemble cystic fibrosis because of mucus plugging,
    poor growth, and gastrointestinal symptoms, but it is distinguished by
    profound congenital hearing loss and biallelic SLC12A2 deficiency.
  distinguishing_features:
  - Profound sensorineural hearing loss and absent salivation favor Kilquist syndrome.
  - Positive CFTR-associated testing and classic pancreatic-pulmonary phenotype favor cystic fibrosis.
- name: Usher syndrome
  disease_term:
    preferred_term: Usher syndrome
    term:
      id: MONDO:0019501
      label: Usher syndrome
  description: >-
    Usher syndrome overlaps with Kilquist syndrome through congenital hearing
    loss, but Kilquist syndrome is distinguished by severe gastrointestinal and
    secretory epithelial dysfunction rather than retinitis pigmentosa.
  distinguishing_features:
  - Global developmental delay and absent epithelial secretions favor Kilquist syndrome.
  - Progressive retinopathy with deafblindness favors Usher syndrome.
clinical_trials: []
datasets:
- accession: PMID:30740830
  title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
  description: >-
    Foundational human case-based dataset defining Kilquist syndrome through
    deep clinical phenotyping, genomic diagnosis, and fibroblast-based
    functional validation of complete NKCC1 loss.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 1
  conditions:
  - Kilquist syndrome
  - homozygous SLC12A2 deletion
  publication: PMID:30740830
  evidence:
  - reference: PMID:30740830
    reference_title: "Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation.
    explanation: >-
      This supports the publication as the foundational disease-defining human
      phenotype dataset for Kilquist syndrome.
notes: >-
  Asta deep research was run as requested, but final curation relied on direct
  review of PubMed references because the retrieval output was noisy and only
  partially disease-specific.