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Filippi syndrome

General Information (adopted from Orphanet):

Synonyms, Signs:	SCOTT CRANIODIGITAL SYNDROME WITH MENTAL RETARDATION FILIPPI SYNDROME Syndactyly type 1 - microcephaly - intellectual deficit
Number of Symptoms	44
OrphanetNr:	3255
OMIM Id:	272440
ICD-10:	Q87.8
UMLs:	C0795940
MeSH:	C538152
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	< 25 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Neonatal Infancy [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Multiple congenital anomalies/dysmorphic syndrome-intellectual deficit
-Rare developmental defect during embryogenesis
-Rare genetic disease
Rare genetic intellectual deficit with developmental anomaly
-Rare genetic disease
Rare intellectual deficit with developmental anomaly
-Rare neurologic disease
Syndrome with limb duplication, polydactyly, syndactyly, and/or hyperphalangy
-Rare bone disease
-Rare developmental defect during embryogenesis

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000028)	Cryptorchidism		347 / 7739
2	(HPO:0000035)	Abnormality of the testis	Very frequent [Orphanet]	296 / 7739
3	(HPO:0000062)	Ambiguous genitalia	rare [HPO:skoehler]	74 / 7739
4	(HPO:0000520)	Proptosis		192 / 7739
5	(HPO:0000322)	Short philtrum		130 / 7739
6	(HPO:0000252)	Microcephaly	Very frequent [Orphanet]	832 / 7739
7	(HPO:0000431)	Wide nasal bridge		290 / 7739
8	(HPO:0000445)	Wide nose	Very frequent [Orphanet]	190 / 7739
9	(HPO:0000668)	Hypodontia	rare [HPO:skoehler]	81 / 7739
10	(HPO:0000337)	Broad forehead		116 / 7739
11	(HPO:0000430)	Underdeveloped nasal alae	Very frequent [Orphanet]	90 / 7739
12	(HPO:0000426)	Prominent nasal bridge	Very frequent [Orphanet]	121 / 7739
13	(HPO:0000233)	Thin vermilion border		124 / 7739
14	(HPO:0002007)	Frontal bossing	Frequent [Orphanet]	366 / 7739
15	(HPO:0000691)	Microdontia		104 / 7739
16	(HPO:0000648)	Optic atrophy		238 / 7739
17	(HPO:0000505)	Visual impairment		297 / 7739
18	(HPO:0001249)	Intellectual disability		1089 / 7739
19	(HPO:0001250)	Seizures		1245 / 7739
20	(HPO:0002167)	Neurological speech impairment	Very frequent [Orphanet]	308 / 7739
21	(HPO:0001332)	Dystonia		197 / 7739
22	(HPO:0002750)	Delayed skeletal maturation	Frequent [Orphanet]	250 / 7739
23	(HPO:0006101)	Finger syndactyly	Very frequent [Orphanet]	198 / 7739
24	(HPO:0000954)	Single transverse palmar crease	Frequent [Orphanet]	162 / 7739
25	(HPO:0004209)	Clinodactyly of the 5th finger	Very frequent [Orphanet]	288 / 7739
26	(HPO:0010714)	2-4 toe syndactyly		2 / 7739
27	(HPO:0004322)	Short stature	Very frequent [Orphanet]	1232 / 7739
28	(HPO:0008897)	Postnatal growth retardation		113 / 7739
29	(HPO:0001511)	Intrauterine growth retardation		358 / 7739
30	(HPO:0004325)	Decreased body weight		492 / 7739
31	(HPO:0008070)	Sparse hair	rare [HPO:skoehler]	94 / 7739
32	(HPO:0000998)	Hypertrichosis	rare [HPO:skoehler]	52 / 7739
33	(HPO:0001629)	Ventricular septal defect		316 / 7739
34	(OMIM)	Megacisterna magna (rare)		1 / 7739
35	(OMIM)	Dystonic tongue protrusion		1 / 7739
36	(OMIM)	Prominent columella		4 / 7739
37	(OMIM)	Retrobulbar venous varix		1 / 7739
38	(HPO:0000007)	Autosomal recessive inheritance		2538 / 7739
39	(HPO:0012758)	Neurodevelopmental delay	Very frequent [Orphanet]	949 / 7739
40	(OMIM)	Straight mouth		1 / 7739
41	(OMIM)	Arachnoidal cyst		2 / 7739
42	(OMIM)	Diffuse enlargement of subarachnoid spaces and lateral ventricles (rare)		1 / 7739
43	(HPO:0001272)	Cerebellar atrophy		197 / 7739
44	(OMIM)	Hairy forehead		1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Scott et al. (1971) described a craniodigital syndrome with mental retardation in 3 brothers. The mother and the maternal grandmother had soft tissue syndactyly between toes 2 and 3. The father and mother were 46 and 31 years ... Scott et al. (1971) described a craniodigital syndrome with mental retardation in 3 brothers. The mother and the maternal grandmother had soft tissue syndactyly between toes 2 and 3. The father and mother were 46 and 31 years old, respectively, at the birth of their first child. Somatic and mental development was delayed. From birth the facies were abnormal with brachycephaly, small and narrow nose, 'startled' appearance, thick head hair with extension of the hair unusually far on the temples and sideburn areas, long eyelashes, thick eyebrows, and somewhat short mandible. The digital anomalies were soft-tissue syndactyly between toes 2 and 3 and between fingers 2, 3, and 4. The dermatoglyphic patterns on the hands were considered unusual. Because the disorder occurred in 3 brothers, Scott et al. (1971) suggested X-linked inheritance. Filippi (1985) described an apparently distinct syndrome in 3 (2 boys, 1 girl) of 8 sibs with healthy, unrelated parents. The affected individuals had striking syndactyly of fingers 3 and 4, clinodactyly of the fifth finger, and syndactyly of toes 2, 3 and 4. There was microcephaly and severe physical and mental retardation. The nose had a broad base resembling that in Waardenburg syndrome. Lorenz et al. (1990) reported what they designated the craniofacial digital syndrome of Scott in a boy whose mother had bilateral cutaneous syndactyly of toes 2 and 3. Photographs of the hands in the boy showed syndactyly of fingers 2, 3, and 4 (especially 3 and 4) and syndactyly of toes 2-4. The syndactyly of the toes in the mother appeared in a photograph to have been very mild. Zerres et al. (1992) described a 2-year-old boy with mental retardation, postnatal short stature, postnatal microcephaly, a small atrial septal defect, dysmorphic face, syndactyly 2/5 of the hands and 1/4 of the feet, and brachymesophalangy of fingers 2 and 5. Meinecke (1993) described an 18-year-old boy and his 15-year-old sister with the same syndrome. They showed pre- and postnatal short stature, microcephaly, moderate to severe mental retardation, and cutaneous syndactyly of hands and feet. In addition, they showed a mildly dysmorphic but apparently characteristic face. Radiologically, the hands and feet showed brachydactyly, the metacarpals and metatarsals being the most severely affected. Toriello and Higgins (1995) concluded that the appropriate diagnosis was Filippi syndrome in a boy who showed low birth weight, congenital microcephaly, multiple minor facial anomalies, cleft palate, soft tissue syndactyly of fingers and toes, and moderate to severe mental retardation. Heron et al. (1995) reported the case of a 9-year-old girl, born to first-cousin Tunisian parents, with microcephaly, cutaneous syndactyly of the toes, and moderate mental retardation with marked speech involvement. The face showed high nasal root and skeletal anomalies were demonstrated radiologically: hypoplasia of radial heads and dislocation of the elbows; synostosis of 2 carpal bones, and brachymesophalangism of the fifth fingers. Fryer (1996) described 2 brothers with pre- and postnatal growth retardation, microcephaly, syndactyly of fingers and toes (only feet were affected in the younger brother), cryptorchidism, and only minimal learning difficulties. Williams et al. (1999) described 3 unrelated patients with Filippi syndrome. All had microcephaly, minor facial anomalies, variable syndactyly of the digits, growth impairment, and developmental delay. One patient also had polydactyly, which had not previously been reported in Filippi syndrome. Franceschini et al. (2002) reported a patient with the characteristic features of Filippi syndrome. They compared her features with those of other reported patients, including 11 males and 5 females, and underscored the peculiar and specific shape of the nasal bridge. A high nasal bridge was found to be present from an early age. The metacarpophalangeal profile showed a peculiar shortness of all metacarpals and of the proximal first phalanx. Franceschini et al. (2002) also compared the clinical findings in all 17 cases of Filippi syndrome with those in other 'craniodigital syndromes.' Schorderet et al. (2002) described 2 brothers of Bosniak origin with syndactyly of the fingers and/or toes, cerebellar atrophy, axial hypotonia, limb hypertonia, and severe mental retardation. Sharif and Donnai (2004) reported 2 unrelated children with Filippi syndrome. Both showed typical facial dysmorphism, syndactyly of fingers and toes, growth retardation, postnatal microcephaly and developmental delay, particularly involving speech. In addition, both children had unusual teeth and hair. The authors proposed that neurologic and ectodermal involvement may be underrecognized features of the syndrome. Milani et al. (2007) reported a girl, born of unrelated Italian patients, with a phenotype most reminiscent of Scott syndrome. She showed intrauterine growth retardation during the second semester and had microsomia with small body and microcephaly at age 3 years. She had severely delayed psychomotor development, learned to walk at 3.5 years, and showed poor social interaction and stereotyped movements. Dysmorphic features included fine hair, synophrys, long eyelashes, hypertelorism, bulbous nasal tip, anteverted ears with hyperconvoluted helix, shallow philtrum, thin lips, small and widely spaced teeth, and generalized hirsutism. Severe syndactyly of toes 2 and 3 was present bilaterally, which was also found in the mother and paternal grandfather. Brain MRI showed Chiari type I malformation. She had a single seizure at age 4 years. In addition, her bone age was delayed, and Milani et al. (2007) noted that the patient reported by Lorenz et al. (1990) also had delayed bone age. Although Milani et al. (2007) favored dominant inheritance of the disorder with variable expressivity, the occurrence of the disorder in a female argues against this (Sobreira, 2013). Battaglia et al. (2008) published MRI images of a child with Filippi syndrome, the offspring of healthy nonconsanguineous parents, which showed diffuse enlargement of subarachnoid spaces and lateral ventricles and the presence of a megacisterna magna. For similar craniodigital syndromes, see 251255 and 615236.

Symptoms & Signs

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