ORPHA:615954

Lethal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome

Synonyms: Fatal pontocerebellar hypoplasia-hypotonia-respiratory distress syndrome · Fatal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome

Type: Clinical syndrome
Group: Disorder
Age of onset: Antenatal, Neonatal
Status: active

A rare multiple congenital anomalies/dysmorphic syndrome characterized by pontocerebellar hypoplasia, hypotonia and respiratory insufficiency. Cardiac anomalies (particularly hypertrophic cardiomyopathy), eye manifestations (congenital cataracts, corneal clouding), seizures and facial dysmorphism (including microcephaly, bitemporal narrowing, absence of eyelashes, short palpebral fissures, small and low-set ears, anteverted nares, microstomia, and micrognathia) are present in the majority of the patients. Additional findings such as hepatosplenomegaly, edema, micropenis/cryptorchidism, hypoglycemia, hypernatremia, increased triglycerides, elevated plasma lactate and decreased plasma cholesterol were reported. Brain imaging may reveal simplified/delayed cortical gyration, dilated ventricles, and periventricular or diffuse white matter abnormalities. It is mostly caused by biallelic deletions in the ATAD3 gene cluster (ATAD3A, ATAD3B and ATAD3C) or by point mutations in the ATAD3A gene. Even though the syndrome is mostly neonatally lethal, some patients, regardless of the type of the mutation/deletion they harbor, may have a less severe condition and may survive.

Names in Orphadata languages

10 of 12 languages

Lang	Name	Synonyms
en	Lethal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome	Fatal pontocerebellar hypoplasia-hypotonia-respiratory distress syndrome · Fatal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome
fr	Syndrome létal d'hypoplasie pontocérébelleuse-hypotonie-insuffisance respiratoire	Syndrome fatal d'hypoplasie pontocérébelleuse-hypotonie-détresse respiratoire
de	Syndrom der letalen pontozerebellären Hypoplasie mit Hypotonie und respiratorischer Insuffizienz	Fatale pontozerebelläre Hypoplasie-Hypotonie-Atemwegsinsuffizienz-Syndrom
es	Síndrome letal de hipoplasia pontocerebelosa-hipotonía-insuficiencia respiratoria	Síndrome fatal de hipoplasia pontocerebelosa-hipotonía-distrés respiratorio · Síndrome fatal de hipoplasia pontocerebelosa-hipotonía-insuficiencia respiratoria
it	Sindrome letale da ipoplasia pontocerebellare, ipotonia e insufficienza respiratoria	Sindrome letale da ipoplasia pontocerebellare, ipotonia e distress respiratorio
nl	Letaal pontocerebellaire hypoplasie - hypotonie - respiratoire insufficiëntie-syndroom	Fataal pontocerebellaire hypoplasie - hypotonie - ademnood-syndroom · Fataal pontocerebellaire hypoplasie - hypotonie - respiratoire insufficiëntie-syndroom
pt	Síndrome letal de hipoplasia pontocerebelosa-hipotonia-insuficiência respiratória	Síndrome fatal de hipoplasia pontocerebelosa-hipotonia-dificuldade respiratória · Síndrome fatal de hipoplasia pontocerebelosa-hipotonia-insuficiência respiratória
pl	Letalny zespół hipoplazja mostowo-móżdżkowa-hipotonia-niewydolność oddechowa	= en
cs	Syndrom zahrnující letální pontocerebelární hypoplázii, hypotonii a respirační insuficienci	= en
uk	Летальний синдром понтоцеребеллярної гіпоплазії-гіпотонії-дихальної недостатності	Фатальна понтоцеребеллярна гіпоплазія-гіпотонія-респіраторний дистрес-синдром · Фатальний синдром понтоцеребеллярної гіпоплазії-гіпотонії-дихальної недостатності

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	618810	E		validated
ICD-10	Q04.8	NTBT	attributed	validated
ICD-11	LD20.0Y	NTBT	attributed	validated
MONDO	0032931	E		validated
UMLS	C5680387	E		validated

E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.

Classification

Preferential parent (Orphanet linearisation):

ORPHA:93890Rare developmental defect during embryogenesis

Parents in the classifications (3):

ORPHA:471383Genetic lethal multiple congenital anomalies/dysmorphic syndrome
rare genetic diseases
ORPHA:459787Lethal multiple congenital anomalies/dysmorphic syndrome
rare developmental anomalies during embryogenesis
ORPHA:728528Pontocerebellar hypoplasia and related disorders
rare developmental anomalies during embryogenesis; rare genetic diseases; rare neurological diseases

Children (2):

Genes

0 direct · 2 via subtypes

Orphanet records no gene directly on this code.

Recorded by Orphanet on subtypes of this disorder:

Gene	Subtype	Association	Status	HGNC	Ensembl	OMIM	Locus	Name	Source of validation
ATAD3A	ORPHA:615983Lethal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome due to a point mutation	Disease-causing germline mutation(s) in	Assessed	HGNC:25567	ENSG00000197785	612316	1p36.33	ATPase family AAA domain containing 3A	28549128[PMID]
ATAD3A	ORPHA:615986Lethal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome due to biallelic deletions in the ATAD3 gene cluster	Role in the phenotype of	Assessed	HGNC:25567	ENSG00000197785	612316	1p36.33	ATPase family AAA domain containing 3A	27640307[PMID]

Prevalence and incidence

2 records

Type	Class	Value	Area	Qualification	Validation	Source
Cases/families		16 cases	Worldwide	Case(s)	Validated	27640307[PMID]_28549128[PMID]_29053797[PMID]_31727539[PMID]
Point prevalence	<1 / 1 000 000	—	Worldwide	Class only	Validated	27640307[PMID]_28549128[PMID]_29053797[PMID]_31727539[PMID]_ORPHANET

Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.

HPO phenotypes

Orphanet has no HPO annotation for this code in this release.

Sources for this card

Orphanet page: orpha.net/en/disease/detail/615954
This record as JSON: /data/d/615954.json