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hypotonia, infantile, with psychomotor retardation and characteristic facies (IHPRF) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

hypotonia, infantile, with psychomotor retardation and characteristic facies

MONDO:0014176

Also known as:IHPRFIHPRF syndromehypotonia-speech impairment-severe cognitive delay syndrome

Overview

A rare, genetic neurodegenerative disorder characterized by severe, persistent hypotonia (presenting at birth or in early infancy), severe global developmental delay (with poor or absent speech, difficulty or inability to roll, sit or walk), profound intellectual disability, and failure to thrive. Additional manifestations include microcephaly, progressive peripheral spasticity, bilateral strabismus and nystagmus, constipation, and variable dysmorphic facial features (including plagiocephaly, broad forehead, small nose, low-set ears, micrognathia and open mouth with tented upper lip).

OnsetANTENATAL

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: before birth.

GeneReviews

Clinical Guidance

To date, at least 117 individuals have been identified [E Durham, personal observation] and 73 individuals have been reported in the literature with biallelic pathogenic variants in TBCK [, , , , , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. TBCK-Related Neurodevelopmental Disorder: Frequency of Select Features

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

No consensus clinical diagnostic criteria for TBCK-related neurodevelopmental disorder (TBCK-NDD) have been published.

Suggestive Findings

TBCK-NDD should be considered in probands with the following clinical, laboratory, and brain MRI findings and family history.

Clinical findings

Source: GeneReviews — "TBCK-Related Neurodevelopmental Disorder"

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for hypotonia, infantile, with psychomotor retardation and characteristic facies. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for TBCK-related neurodevelopmental disorder (TBCK-NDD) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with TBCK-NDD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. TBCK-Related Neurodevelopmental Disorder: Recommended Surveillance

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for hypotonia, infantile, with psychomotor retardation and characteristic facies.

40 publications have been identified in PubMed for hypotonia, infantile, with psychomotor retardation and characteristic facies. Research spans Case Report / Case Series (57%), Review / Meta-Analysis (25%), and Epidemiology / Natural History (8%).

Research Type	Count	% of Total
Patient case studies	23	57%

Data assembled from 4 of 12 sources · Last updated Sep 21, 2026, 4:55 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:371364

GARD

Genetic and Rare Diseases Info Center

GARD:17609

Questions for Your Care Team

→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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Feature	% of Persons w/Feature	Comment
Severe-to-profound developmental delay/ intellectual disability	100%	—
Severe hypotonia	100%	—
Macroglossia	Up to 90% by age 10 yrs	Progressive w/age
Eye anomalies	90%	—
Cardiovascular	86.6% w/dyslipidemia	Dyslipidemia typically involves hypercholesterolemia /or hypertriglyceridemia
There are a few reports of congenital cardiac structural defects (10 affected persons reported) Aberrant head shape /or size	85.7%	Incl 3/22 (14%) w/microcephaly, 7/22 (32%) w/macrocephaly, 5/22 (23%) w/brachycephaly, 3/22 (14%) w/turricephaly
Respiratory insufficiency/failure	84%	Can be progressive; congenital in fewer than 10%
Osteopenia	84%	Which may predispose to bony fractures
Seizures	76.7%	Onset usually between age 0-3 yrs
Genitourinary findings	60% by age 15 yrs	Typically recurrent urinary tract infections /or nephrolithiasis; renal anomalies not common Developmental delay (DD) and intellectual disability (ID). Gross and fine motor delays are often severe, with a majority of affected individuals unable to ambulate independently during their lifetime.

GeneReviews

Differential Diagnosis

Genetic disorders of interest in the differential diagnosis of TBCK-related neurodevelopmental disorder (TBCK-NDD) are listed in . Note: Most affected individuals exhibit some degree of developmental regression and/or neurologic decompensation in the setting of illness, which often raises clinical concerns for mitochondrial disorders, although the features of TBCK-NDD are not sufficient to suggest a specific monogenic mitochondrial disorder per se. Table 3. Genes of Interest in the Differential Diagnosis of TBCK-Related Neurodevelopmental Disorder

Gene(s)	Disorder	MOI	Features of Disorder
NALCN	Infantile hypotonia w/psychomotor retardation characteristic facies-1 (OMIM 615419)	AR	Hypotonia; Severe DD/ID; Seizures; Peripheral motor neuropathy
NDD w/hypotonia, facial dysmorphism, brain abnormalities	AR	Hypotonia; Severe DD/ID; Coarse dysmorphic features incl macroglossia; Note: Phenotype is very similar to TBCK-NDD (TBCK PPP1R21 are part of same molecular complex).	Blue sclerae SPTBN4
SPTBN4 disorder	AR	Congenital hypotonia; Seizures; Peripheral neuropathy	Auditory neuropathy AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; NDD = neurodevelopmental disorder; TBCK-NDD = TBCK-related neurodevelopmental disorder

Source: GeneReviews — "TBCK-Related Neurodevelopmental Disorder"

Kisho

hypotonia, infantile, with psychomotor retardation and characteristic facies

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Constitutional

Craniofacial

Neurologic

Development

Psychiatric

Musculoskeletal

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

hypotonia, infantile, with psychomotor retardation and characteristic facies

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Constitutional

Craniofacial

Neurologic

Development

Psychiatric

Musculoskeletal

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications