PEHO-like syndrome

Summary

PEHO-like syndrome (MONDO:0020495) is a disease caused by CCDC88A (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CCDC88A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	PEHO-like syndrome
Mondo ID	MONDO:0020495
OMIM	617507
Orphanet	99807
UMLS	C1850056
MedGen	337956
GARD	0016911
Is cancer (heuristic)	no

Also known as: PEHO syndrome-like · peho-like syndrome · PEHOL · progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy-like syndrome

Data availability: 18 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › PEHO-like syndrome

Related subtypes (263): leukoencephalopathy, megalencephalic, epilepsy, familial adult myoclonic, encephalopathy, acute, infection-induced, GLUT1 deficiency syndrome, paraganglioma, familial hemiplegic migraine, stutter disorder, specific language impairment, anencephaly, complex cortical dysplasia with other brain malformations, familial periodic paralysis, tuberous sclerosis, essential tremor, intracranial extraskeletal myxoid chondrosarcoma, Parkinson disease, progressive external ophthalmoplegia, myalgic encephalomeyelitis/chronic fatigue syndrome, cerebral amyloid angiopathy, congenital nystagmus, Angelman syndrome, nevoid basal cell carcinoma syndrome, Chiari malformation type I, choreoathetosis, familial inverted, cluster headache, familial, coloboma of optic nerve, craniosynostosis-Dandy-Walker malformation-hydrocephalus syndrome, major affective disorder 1, neurohypophyseal diabetes insipidus, Duane retraction syndrome, lateral meningocele syndrome, encephalopathy, recurrent, of childhood, familial congenital palsy of trochlear nerve, Gerstmann-Straussler-Scheinker syndrome, Tourette syndrome, Guillain-Barre syndrome, familial, Frey syndrome, melanoma and neural system tumor syndrome, narcolepsy 1, linear nevus sebaceous syndrome, oculocerebrocutaneous syndrome, obsessive-compulsive disorder, paroxysmal extreme pain disorder, familial pterygium of the conjunctiva, retinal detachment, Sturge-Weber syndrome, DiGeorge syndrome, blue color blindness, velocardiofacial syndrome, von Hippel-Lindau disease, arthrogryposis, Chiari malformation type II, Behr syndrome, isolated cerebellar hypoplasia/agenesis, bilateral striopallidodentate calcinosis, Griscelli syndrome type 1, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, Riley-Day syndrome, glutaryl-CoA dehydrogenase deficiency, normal pressure hydrocephalus, hyperlexia, Johanson-Blizzard syndrome, macrocephaly/megalencephaly syndrome, autosomal recessive, neurocutaneous melanocytosis, myosclerosis, Bailey-Bloch congenital myopathy, choroid plexus papilloma, pyridoxine-dependent epilepsy, NPHP3-related Meckel-like syndrome, familial hemophagocytic lymphohistiocytosis type 1, mismatch repair cancer syndrome 1, orofaciodigital syndrome type 6, X-linked immunoneurologic disorder, HSD10 mitochondrial disease, rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked, severe neonatal-onset encephalopathy with microcephaly, dilated cardiomyopathy 3B, red-green color blindness, red color blindness, iris hypoplasia with glaucoma, major affective disorder 2, band heterotopia of brain, Brody myopathy, chorea, remitting, with nystagmus and cataract, isolated hereditary congenital facial paralysis, childhood apraxia of speech, megalencephaly-capillary malformation-polymicrogyria syndrome, familial infantile myoclonic epilepsy, TH-deficient dopa-responsive dystonia, glycine encephalopathy, spongiform encephalopathy with neuropsychiatric features, bilateral frontoparietal polymicrogyria, B4GALT1-congenital disorder of glycosylation, angioid streaks, familial meningioma, biotin-responsive basal ganglia disease, anxiety, rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome, specific phobia, bradyopsia, endogenous depression, narcolepsy 3, permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome, myofibrillar myopathy 5, major affective disorder 3, achromatopsia 6, pyridoxal phosphate-responsive seizures, prosopagnosia, hereditary, brain-lung-thyroid syndrome, polyhydramnios, megalencephaly, and symptomatic epilepsy, major affective disorder 4, major affective disorder 5, major affective disorder 6, major affective disorder 8, major affective disorder 7, major affective disorder 9, age-related hearing impairment 1, bilateral parasagittal parieto-occipital polymicrogyria, age-related hearing impairment 2, combined pituitary hormone deficiencies, genetic form, cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome, rhabdoid tumor predisposition syndrome 2, infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly, schizophrenia 15, schizophrenia 16, occipital pachygyria and polymicrogyria, familial retinal arterial macroaneurysm, narcolepsy 7, bilateral generalized polymicrogyria, myoclonus, familial, familial hyperprolactinemia, proximal myopathy with extrapyramidal signs, sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome, polymicrogyria, bilateral perisylvian, autosomal recessive, ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome, cerebellar-facial-dental syndrome, myopathy due to calsequestrin and SERCA1 protein overload, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, Brown syndrome, epilepsy with myoclonic atonic seizures, polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, TELO2-related intellectual disability-neurodevelopmental disorder, hypermanganesemia with dystonia 2, aniridia 2, aniridia 3, severe congenital nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, myopic macular degeneration, 2-hydroxyglutaric aciduria, benign neonatal seizures, qualitative or quantitative defects of alpha-sarcoglycan, qualitative or quantitative defects of beta-sarcoglycan, qualitative or quantitative defects of gamma-sarcoglycan, qualitative or quantitative defects of delta-sarcoglycan, neuromuscular disease caused by qualitative or quantitative defects of dysferlin, caveolinopathy, neuromuscular disease caused by qualitative or quantitative defects of perlecan, neuromuscular disease caused by qualitative or quantitative defects of TRIM32, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, qualitative or quantitative defects of desmin, neuromuscular disease caused by qualitative or quantitative defects of telethonin, neuromuscular disease caused by qualitative or quantitative defects of beta-myosin heavy chain (MYH7), neuromuscular disease caused by qualitative or quantitative defects of plectin, spastic quadriplegic cerebral palsy, congenital stationary night blindness, holoprosencephaly, congenital hydrocephalus, intracranial berry aneurysm, familial congenital mirror movements, Moebius syndrome-axonal neuropathy-hypogonadotropic hypogonadism syndrome, Moyamoya disease, familial Alzheimer-like prion disease, phakomatosis pigmentokeratotica, benign familial infantile epilepsy, inborn aminoacylase deficiency, familial partial epilepsy, familial isolated pituitary adenoma, Hoyeraal-Hreidarsson syndrome, hereditary retinoblastoma, familial syringomyelia, PrP systemic amyloidosis, Prader-Willi-like syndrome, bilirubin encephalopathy, microcephaly-complex motor and sensory axonal neuropathy syndrome, undetermined early-onset epileptic encephalopathy, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, familial schizencephaly, lissencephaly spectrum disorders, Li-Fraumeni syndrome, multiminicore myopathy, parietal foramina, Ritscher-Schinzel syndrome, inherited retinal dystrophy, folinic acid-responsive seizures, megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome, nonsyndromic genetic hearing loss, progressive myoclonus epilepsy, pontocerebellar hypoplasia, cerebral lipidosis with dementia, inherited vitreoretinopathy, periventricular nodular heterotopia, familial porencephaly, X-linked deafness, hereditary progressive chorea without dementia, hereditary hyperekplexia, neurofibromatosis, inherited orthostatic hypotension, auditory neuropathy, retinal ciliopathy, Behrens Baumann dust syndrome, inherited reflex epilepsy, inherited neurodegenerative disorder, febrile seizures, familial, 11, famililal cerebral cavernous malformations, familial panic disorder, microangiopathy and leukoencephalopathy, pontine, autosomal dominant, schizophrenia 19, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, cathepsin a-related arteriopathy-strokes-leukoencephalopathy, parkinsonism with polyneuropathy, central nervous system lupus, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, inherited dystonia, encephalopathy due to mitochondrial and peroxisomal fission defect, alpha-actinopathy, dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive, TPM3-related myopathy, Uner Tan Syndrome, TUBB3-related tubulinopathy, TTN-related myopathy, TPM2-related myopathy, fatty acyl-CoA reductase 1 upregulation, hereditary ataxia, brain malformations with or without urinary tract defects, Mendelian neurodevelopmental disorder, SPAST-related motor disorder, hereditary neuromuscular disease, SERAC1-related neurological disorder, PRRT2-associated paroxysmal movement disorder, hereditary generalized epilepsy, VPS11-related neurological disorder, KIF5A-related neurological disorder, ATP1A3-associated neurological disorder, myopathy caused by variation in POMGNT1, SLC6A3-related dopamine transporter deficiency syndrome, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, dyskinesia with orofacial involvement, autosomal dominant, PAX6-related ocular dysgenesis, neuroocular syndrome, epilepsy, X-linked, with or without impaired intellectual development and dysmorphic features, encephalopathy, acute transient, LSM7-related leukodystrophy and cerebellar atrophy, infection-induced acute-onset axonal neuropathy, Valence-Farazi cerebellar ataxia syndrome, DHDDS-related syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

18 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 benign, 5 pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1365714	NM_001365480.1(CCDC88A):c.1942del (p.Lys647_Ile648insTer)	CCDC88A	Pathogenic	criteria provided, single submitter
1435609	NM_001365480.1(CCDC88A):c.4161_4162dup (p.Pro1388fs)	CCDC88A	Pathogenic	criteria provided, single submitter
253149	NM_001365480.1(CCDC88A):c.2315del (p.Thr771_Leu772insTer)	CCDC88A	Pathogenic	no assertion criteria provided
3376503	NM_001365480.1(CCDC88A):c.1292G>A (p.Trp431Ter)	CCDC88A	Pathogenic	no assertion criteria provided
3376504	NM_001365480.1(CCDC88A):c.1795_1798del (p.Thr599fs)	CCDC88A	Pathogenic	no assertion criteria provided
1347598	NM_001365480.1(CCDC88A):c.543G>A (p.Met181Ile)	CCDC88A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033728	NM_001365480.1(CCDC88A):c.3263G>C (p.Arg1088Thr)	CCDC88A	Uncertain significance	criteria provided, single submitter
1351927	NM_001365480.1(CCDC88A):c.2603C>T (p.Thr868Ile)	CCDC88A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1356497	NM_001365480.1(CCDC88A):c.3527C>T (p.Ser1176Phe)	CCDC88A	Uncertain significance	criteria provided, single submitter
1683539	NM_001365480.1(CCDC88A):c.3580G>A (p.Glu1194Lys)	CCDC88A	Uncertain significance	criteria provided, single submitter
2439806	NM_001365480.1(CCDC88A):c.432A>C (p.Arg144Ser)	CCDC88A	Uncertain significance	criteria provided, single submitter
2439807	NM_001365480.1(CCDC88A):c.1340A>G (p.Gln447Arg)	CCDC88A	Uncertain significance	criteria provided, single submitter
1167007	NM_001365480.1(CCDC88A):c.882+20G>A	CCDC88A	Benign	criteria provided, multiple submitters, no conflicts
1170918	NM_001365480.1(CCDC88A):c.344-9C>T	CCDC88A	Benign	criteria provided, multiple submitters, no conflicts
1192541	NM_001365480.1(CCDC88A):c.4745-53C>T	CCDC88A	Benign	criteria provided, multiple submitters, no conflicts
1192542	NM_001365480.1(CCDC88A):c.4744+85T>G	CCDC88A	Benign	criteria provided, multiple submitters, no conflicts
1192543	NM_001365480.1(CCDC88A):c.800+31T>A	CCDC88A	Benign	criteria provided, multiple submitters, no conflicts
1534144	NM_001365480.1(CCDC88A):c.403-7A>G	CCDC88A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CCDC88A	Strong	Autosomal recessive	PEHO-like syndrome	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCDC88A	Orphanet:99807	PEHO-like syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CCDC88A	HGNC:25523	ENSG00000115355	Q3V6T2	Girdin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCDC88A	Girdin	Bifunctional modulator of guanine nucleotide-binding proteins (G proteins).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CCDC88A	Other/Unknown	no		CH_dom, CH_dom_sf, HOOK_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	1
cortical plate	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCDC88A	250	ubiquitous	marker	medial globus pallidus, corpus callosum, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCDC88A	1,471

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCDC88A	Q3V6T2	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RND1 GTPase cycle	1	265.6×	0.004	CCDC88A
RND3 GTPase cycle	1	259.6×	0.004	CCDC88A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maintenance of protein location in plasma membrane	1	8426.0×	0.002	CCDC88A
positive regulation of protein localization to cilium	1	2808.7×	0.003	CCDC88A
activation of protein kinase activity	1	1532.0×	0.004	CCDC88A
cytoskeleton-dependent intracellular transport	1	936.2×	0.004	CCDC88A
TOR signaling	1	766.0×	0.004	CCDC88A
positive regulation of cilium assembly	1	766.0×	0.004	CCDC88A
membrane organization	1	510.7×	0.004	CCDC88A
positive regulation of epidermal growth factor receptor signaling pathway	1	495.6×	0.004	CCDC88A
lamellipodium assembly	1	443.5×	0.004	CCDC88A
regulation of neuron projection development	1	432.1×	0.004	CCDC88A
cytoplasmic microtubule organization	1	343.9×	0.005	CCDC88A
positive regulation of stress fiber assembly	1	312.1×	0.005	CCDC88A
small GTPase-mediated signal transduction	1	183.2×	0.008	CCDC88A
regulation of actin cytoskeleton organization	1	157.5×	0.008	CCDC88A
regulation of cell population proliferation	1	115.4×	0.010	CCDC88A
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.014	CCDC88A
cell migration	1	61.5×	0.017	CCDC88A
nervous system development	1	45.9×	0.022	CCDC88A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCDC88A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CCDC88A

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CCDC88A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.