Severe achondroplasia - developmental delay - acanthosis nigricans

General Information (adopted from Orphanet):

Synonyms, Signs: THANATOPHORIC DYSPLASIA
LETHAL SHORT-LIMBED PLATYSPONDYLIC DWARFISM, SAN DIEGO TYPE ACHONDROPLASIA, SEVERE, WITH DEVELOPMENTAL DELAY AND ACANTHOSIS NIGRICANS, INCLUDED
PLATYSPONDYLIC LETHAL SKELETAL DYSPLASIA, SAN DIEGO TYPE
SADDAN, INCLUDED
SADDAN
THANATOPHORIC DWARFISM
TD
TD1
Number of Symptoms 30
OrphanetNr: 85165
OMIM Id: 187600
ICD-10: Q77.4
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 4 cases [Orphanet]
Inheritance: Autosomal dominant
[Orphanet]
Age of onset: Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: FGFR3-related chondrodysplasia
 -Rare genetic disease
Other epidermis disorder
 -Rare skin disease
Other genetic epidermal disease
 -Rare genetic disease
Primary bone dysplasia with micromelia
 -Rare bone disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
(HPO:0002677) Small foramen magnum 4 / 7739
2
(HPO:0000256) Macrocephaly 298 / 7739
3
(HPO:0000274) Small face 18 / 7739
4
(HPO:0002007) Frontal bossing 366 / 7739
5
(HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
6
(HPO:0000910) Wide-cupped costochondral junctions 3 / 7739
7
(HPO:0000774) Narrow chest 167 / 7739
8
(HPO:0002991) Abnormality of the fibula Frequent [Orphanet] 49 / 7739
9
(HPO:0000773) Short ribs 70 / 7739
10
(HPO:0003185) Short sacroiliac notch 7 / 7739
11
(HPO:0002992) Abnormality of the tibia Frequent [Orphanet] 51 / 7739
12
(HPO:0006660) Aplastic clavicles Frequent [Orphanet] 70 / 7739
13
(HPO:0000924) Abnormality of the skeletal system Very frequent [Orphanet] 114 / 7739
14
(HPO:0004565) Severe platyspondyly 13 / 7739
15
(HPO:0000946) Hypoplastic ilia 21 / 7739
16
(HPO:0002823) Abnormality of the femur Frequent [Orphanet] 61 / 7739
17
(HPO:0006584) Small abnormally formed scapulae 4 / 7739
18
(HPO:0001561) Polyhydramnios 191 / 7739
19
(HPO:0008909) Lethal short-limbed short stature 4 / 7739
20
(HPO:0004763) Paroxysmal supraventricular tachycardia 10 / 7739
21
(HPO:0002093) Respiratory insufficiency 410 / 7739
22
(OMIM) Profound mental retardation and hypotonia in survivors 2 / 7739
23
(HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
24
(OMIM) Temporal lobe heterotopias 2 / 7739
25
(OMIM) Prenatal diagnosis by ultrasound 5 / 7739
26
(OMIM) Marked shortness and bowing of long bones 2 / 7739
27
(HPO:0000238) Hydrocephalus 278 / 7739
28
(OMIM) Cloverleaf skull rarely 2 / 7739
29
(OMIM) 'French telephone receiver femurs' 2 / 7739
30
(OMIM) Severe growth deficiency in survivors 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Thanatophoric dysplasia is a severe short-limb dwarfism syndrome that is usually lethal in the perinatal period. Norman et al. (1992) classified cases of TD into subtypes based on the presence of curved as opposed to straight femurs; patients ...
Diagnosis OMIM - Prenatal Diagnosis

In utero diagnosis was demonstrated by Keats et al. (1970).

Although prenatal diagnosis of TD had been accomplished by ultrasonography in the second trimester (Schild et al., 1996), it was not ...

Clinical Description OMIM Maroteaux et al. (1967) referred to patients with micromelic dwarfism who died in the first hours of life as having 'thanatophoric dwarfism.' The ribs and bones of the extremities were very short and the vertebral bodies were greatly ...
Genotype-Phenotype Correlations OMIM Wilcox et al. (1998) examined the clinical, radiographic, and histologic findings in 91 cases with FGFR3 mutations from the International Skeletal Dysplasia Registry. The most common mutation was R248C (134934.0005), occurring in 45 (50%) cases, and the second ...
Molecular genetics OMIM Reardon et al. (1994) noted that fibroblast growth factor receptor-3 (FGFR3; 134934), which is mutant in achondroplasia, is structurally very similar to FGFR2. Their observation that FGFR2 mutations cause craniosynostosis suggested to them that the lethal skeletal disorder ...
Population genetics OMIM Camera and Mastroiacovo (1982) identified 13 cases of thanatophoric dysplasia among 217,061 Italian births. All were sporadic. In the same series, there were 8 cases of achondroplasia (100800) and 1 case each of camptomelic dysplasia (114290), Ellis-van Creveld ...
Diagnosis GeneReviews Thanatophoric dysplasia (TD) is one of the short-limb dwarfism conditions suspected when significantly shortened long bones and a narrow thorax are detected prenatally or neonatally, especially when perinatal death occurs....
Clinical Description GeneReviews Thanatophoric dysplasia (TD) types I and II are diagnosed prenatally or in the immediate newborn period. Both subtypes are considered lethal skeletal dysplasias; most affected infants die of respiratory insufficiency in the first hours or days of life. Respiratory insufficiency may be secondary to a small chest cavity and lung hypoplasia, compression of the brain stem by the small foramen magnum, or a combination of both. Some affected children have survived into childhood with aggressive ventilatory support....
Genotype-Phenotype Correlations GeneReviews TD types I and II do not share common FGFR3 mutations [Wilcox et al 1998, Brodie et al 1999, Camera et al 2001]. ...
Differential Diagnosis GeneReviews Disorders to consider in the differential diagnosis of thanatophoric dysplasia (TD) [Passos-Bueno et al 1999, De Biasio et al 2000, Lee et al 2002, Neumann et al 2003]:...
Management GeneReviews To establish the extent of disease in a newborn diagnosed with thanatophoric dysplasia (TD), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....