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Diaphragmatic defect - limb deficiency - skull defect

General Information (adopted from Orphanet):

Synonyms, Signs:	FROSTER SYNDROME Froster-Huch syndrome
Number of Symptoms	32
OrphanetNr:	2141
OMIM Id:	601163
ICD-10:	Q87.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	4 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Antenatal Neonatal [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
-Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
-Rare developmental defect during embryogenesis
Syndromic diaphragmatic or abdominal wall malformation
-Rare abdominal surgical disease
-Rare developmental defect during embryogenesis
Syndromic diaphragmatic or thoracic malformation
-Rare surgical thoracic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000130)	Abnormality of the uterus	Occasional [Orphanet]	86 / 7739
2	(HPO:0000029)	Testicular atrophy		13 / 7739
3	(HPO:0004331)	Decreased skull ossification	Very frequent [Orphanet]	31 / 7739
4	(HPO:0000316)	Hypertelorism		644 / 7739
5	(HPO:0000463)	Anteverted nares		305 / 7739
6	(HPO:0000369)	Low-set ears		372 / 7739
7	(HPO:0009466)	Radial deviation of finger	Very frequent [Orphanet]	101 / 7739
8	(HPO:0000912)	Sprengel anomaly	Very frequent [Orphanet]	51 / 7739
9	(HPO:0002817)	Abnormality of the upper limb	Very frequent [Orphanet]	25 / 7739
10	(HPO:0002997)	Abnormality of the ulna	Very frequent [Orphanet]	75 / 7739
11	(HPO:0003063)	Abnormality of the humerus	Very frequent [Orphanet]	36 / 7739
12	(HPO:0004209)	Clinodactyly of the 5th finger		288 / 7739
13	(HPO:0001159)	Syndactyly		140 / 7739
14	(HPO:0002991)	Abnormality of the fibula	Very frequent [Orphanet]	49 / 7739
15	(HPO:0006101)	Finger syndactyly	Very frequent [Orphanet]	198 / 7739
16	(HPO:0002823)	Abnormality of the femur	Very frequent [Orphanet]	61 / 7739
17	(HPO:0002818)	Abnormality of the radius	Very frequent [Orphanet]	96 / 7739
18	(HPO:0001770)	Toe syndactyly		149 / 7739
19	(HPO:0002814)	Abnormality of the lower limb	Very frequent [Orphanet]	23 / 7739
20	(HPO:0000776)	Congenital diaphragmatic hernia		36 / 7739
21	(HPO:0001539)	Omphalocele	Very frequent [Orphanet]	102 / 7739
22	(HPO:0002566)	Intestinal malrotation		89 / 7739
23	(HPO:0000775)	Abnormality of the diaphragm	Very frequent [Orphanet]	62 / 7739
24	(HPO:0002101)	Abnormal lung lobation	Very frequent [Orphanet]	33 / 7739
25	(HPO:0002089)	Pulmonary hypoplasia		80 / 7739
26	(OMIM)	Limb hypoplasia		2 / 7739
27	(OMIM)	Pulmonary hypoplasia associated with diaphragmatic hernia		1 / 7739
28	(MedDRA:10053652)	Limb deformity		2 / 7739
29	(HPO:0000007)	Autosomal recessive inheritance		2538 / 7739
30	(HPO:0040065)	Abnormal morphology of bones of the upper limbs	Very frequent [Orphanet]	25 / 7739
31	(OMIM)	Limb amelia		2 / 7739
32	(OMIM)	Hypertelorism, mild		11 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Froster et al. (1996) described a 'possibly new' autosomal recessive syndrome in 4 successive fetuses (2 females; 2 males) from a healthy nonconsanguineous couple. Both prenatal and postnatal findings were reported. The spectrum of malformations included diaphragmatic defects, ... Froster et al. (1996) described a 'possibly new' autosomal recessive syndrome in 4 successive fetuses (2 females; 2 males) from a healthy nonconsanguineous couple. Both prenatal and postnatal findings were reported. The spectrum of malformations included diaphragmatic defects, hypoplastic lungs, omphalocele, limb deficiencies, syndactyly of toes, and ossification defect of the skull. The specific spectrum of anomalies was not fully compatible with that of any established syndrome. No prenatal exposure to any possible teratogen was found. The limb anomalies were more severe in the 2 last born fetuses. The diaphragmatic defect, which was of postural lateral Bochdalek type, was found in all 4. Gonadal mosaicism in 1 parent was mentioned as a possible alternative to autosomal recessive inheritance. Koifman et al. (2009) reported a female fetus diagnosed prenatally with left diaphragmatic hernia and absence of the right femur. Family history was unremarkable and the parents were not related. The pregnancy was terminated, and on autopsy the fetus was found to have complete absence of the right femur and a left diaphragmatic hernia. The only other abnormality observed was bilateral fifth finger clinodactyly. The authors proposed that the infant had the same condition as the sibs reported by Froster et al. (1996) and suggested that the condition be called Froster syndrome. Gardham et al. (2013) reported 2 sibs, born to healthy nonconsanguineous parents, with features similar to those in the patients reported by Froster et al. (1996) and Koifman et al. (2009). The first, a male fetus, was found on prenatal ultrasonography to have multiple congenital anomalies. Pathologic examination following pregnancy termination showed bilateral diaphragmatic hernia, limb hypoplasia, omphalocele, partial intestinal malrotation, absent right pelvic bone with a single long bone in the right leg, and right testicular atrophy. In addition, the fetus had mild hypertelorism, low-set ears, and an upturned nose. The second sib, a female fetus, was also found on prenatal ultrasonography to have a diaphragmatic hernia. Following pregnancy termination, pathologic examination showed bilateral diaphragmatic hernia with lung hypoplasia. No other abnormalities were observed. A maternally inherited 1.2-Mb duplication in chromosome 8p22 was seen in the female sib on oligonucleotide microarray, but was believed to be a benign copy number variant.

Symptoms & Signs

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