601
(68.2%)

Osteopathia striata-cranial sclerosis syndrome

Abnormality of the metaphysis Cleft palate Epicanthus Micrognathia

X-linked dominant inheritance

Osteopathia striata with cranial sclerosis (OS-CS) is a bone dysplasia characterized by longitudinal striations of the metaphyses of the long bones, sclerosis of the craniofacial bones, macrocephaly, cleft palate and hearing loss.

602
(68.2%)

Lowry-MacLean syndrome

Cleft palate Downslanted palpebral fissures Micrognathia Single transverse palmar crease

Lowry-MacLean syndrome is a very rare syndrome characterized by microcephaly, craniosynostosis, glaucoma, growth failure and visceral malformations.

603
(68.2%)

Sparse hair-short stature-skin anomalies syndrome

Short thumb Single median maxillary incisor

Sparse hair-short stature-skin anomalies syndrome combines short stature, sparse hair, skin hyperpigmentation and urticaria-like reactions on the hands and arms. An upper central incisor, hypoplastic thumbs and/or palmoplantar hyperkeratosis may also be present. It is thought to be a rare form of ectodermal dysplasia and has been described at least once in a mother and her three sons. Transmission is autosomal dominant, or X-linked.

603
(68.2%)

Autosomal dominant deafness-onychodystrophy syndrome

Abnormality of the dentition Short thumb

Autosomal dominant inheritance

Dominant deafness-onychodystrophy (DDOD) syndrome is a multiple congenital anomalies syndrome characterized by congenital hearing impairment, small or absent nails on the hands and feet, and small terminal phalanges.

603
(68.2%)

Vitamin K antagonist embryofetopathy

Macroglossia Short distal phalanx of finger

Vitamin K antagonist embryofetopathy is characterized by a group of symptoms that may be observed in a fetus or newborn when the mother has taken oral vitamin K antagonists, such as warfarin during pregnancy. Vitamin K antagonists are anticoagulant drugs that provide efficient thromboprophylaxis and that can cross the placenta. 5-12 % of infants exposed to warfarin between 6-9 weeks gestation present nasal hypoplasia and skeletal abnormalities, including short limbs and digits (brachydactyly), and stippled epiphyses. Warfarin fetopathy with central nervous system abnormalities (hydrocephalus, intellectual disability, spasticity, and hypotonia) or ocular abnormalities (microphthalmia, cataract, optic atrophy), fetal loss, and stillbirth, occurs in infants exposed at later gestations. Additional features that have been reported after in utero warfarin exposure include facial dysmorphism (cleft lip and/or palate, malformed ears), choanal atresia or stenosis, aorta coarctation, situs inversus totalis, bilobed lungs, and ventral midline dysplasia.

603
(68.2%)

Pycnodysostosis

Abnormality of the dentition Short distal phalanx of finger Short toe

Autosomal recessive inheritance

Pycnodysostosis is a genetic lysosomal disease characterized by osteosclerosis of the skeleton, short stature and brittle bones.

607
(68.2%)

Spondyloepimetaphyseal dysplasia congenita, Strudwick type

Cleft palate Hypoplasia of the odontoid process Micromelia Short femoral neck

Autosomal dominant inheritance

Spondyloepimetaphyseal dysplasia congenita, Strudwick type is characterized by disproportionate short stature from birth (with a very short trunk and shortened limbs) and skeletal abnormalities (lordosis, scoliosis, flattened vertebrae, pectus carinatum, coxa vara, clubfoot, and abnormal epiphyses or metaphyses).

608
(68.2%)

Lissencephaly type 3-metacarpal bone dysplasia syndrome

Facial edema Short distal phalanx of finger Short metacarpal

Autosomal recessive inheritance

This syndrome is characterised by severe microcephaly, agyria, agenesis of the corpus callosum, cerebellar hypoplasia, facial dysmorphology and epiphyseal stippling of the metacarpal bones. It has been described in two brothers. The syndrome is transmitted as an autosomal recessive trait and may be an allelic variant of Neu-Laxova syndrome and Lissencephaly type III with cystic dilations of the cerebellum and foetal akinesia sequence (see these terms).

609
(68.2%)

Metaphyseal anadysplasia

Abnormality of the metaphysis Abnormality of the ulna Aplasia/Hypoplasia of the radius

Metaphyseal anadysplasia is a very rare form of metaphyseal dysplasia characterized by short stature, rhizomelic micromelia and a mild varus deformity of the legs evident from the first months of life, that is associated with radiological features of severe metaphyseal changes (irregularities, widening and marginal blurring) in long bones, most prominent in proximal femurs, and generalized osteopenia, and that usually spontaneously resolves by the age of three years. Severe autosomal dominant and milder recessive variants have been observed.

609
(68.2%)

Femur-fibula-ulna complex

Abnormality of the ulna Micromelia Short humerus Split hand

Femur-fibula-ulna (FFU) complex is a non-lethal congenital anomaly of unknown etiology, more frequently reported in males than females, characterized by a highly variable combination of defects of the femur, fibula, and/or ulna, with striking asymmetry, including absence of the proximal part of the femur, absence of the fibula and malformation of the ulnar side of the upper limb. Axial skeleton, internal organs and intellectual function are usually normal.

609
(68.2%)

Weismann-Netter syndrome

Abnormality of the thyroid gland Abnormality of the ulna Aplasia/Hypoplasia of the radius

Autosomal dominant inheritance

Weismann-Netter syndrome is a rare, genetic, primary, bent bone dysplasia characterized by anterior diaphyseal bowing of the tibia and fibula, broadening of the fibula, posterior cortical thickening of both bones and short stature. Additional skeletal abnormalities include scoliosis with marked lumbar lordosis, horizontal sacrum and square iliac wings and/or, less frequently, vertebral malformations, abnormal shape of the clavicles and ribs, calvarial hyperostosis and delayed eruption of permanent teeth. Delayed ambulation is also frequently associated.

612
(68.1%)

Thrombotic thrombocytopenic purpura

Absent radius Facial edema Keratoconjunctivitis

Thrombotic thrombocytopenic purpura (TTP) is an aggressive and life-threatening form of thrombotic microangiopathy (TMA; see this term) characterized by profound peripheral thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and organ failure of variable severity and is comprised of congenital TTP and acquired TTP (see these terms).

613
(68.1%)

Hypohidrotic ectodermal dysplasia

Cutaneous syndactyly Hypoplasia of the maxilla Keratoconjunctivitis sicca Thick vermilion border

Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder of ectoderm development characterized by malformation of ectodermal structures such as skin, hair, teeth and sweat glands. It comprises three clinically almost indistinguishable subtypes with impaired sweating as the key symptom: Christ-Siemens-Touraine (CST) syndrome (X-linked), autosomal recessive (AR), and autosomal dominant (AD) HED, as well as a fourth rare subtype with immunodeficiency as the key symptom (HED with immunodeficiency) (see these terms).

614
(68.1%)

X-linked intellectual disability-cubitus valgus-dysmorphism syndrome

Downslanted palpebral fissures Malar flattening Short philtrum Tapered finger

X-linked recessive inheritance

X-linked intellectual disability-cubitus valgus-dysmorphism syndrome is characterised by moderate intellectual deficit, marked cubitus valgus, mild microcephaly, a short philtrum, deep-set eyes, downslanting palpebral fissures and multiple nevi. Less than ten individuals have been described so far. Transmission is thought to be X-linked recessive.

614
(68.1%)

X-linked intellectual disability, Brooks type

Epicanthus inversus Malar flattening Tapered finger Thin upper lip vermilion

X-linked recessive inheritance

X-linked intellectual disability, Brooks type is a rare X-linked intellectual disability syndrome characterized by failure to thrive, speech delay, intellectual disability, muscle hypotonia, spastic diplegia, optic atrophy with myopia, and distinct facial features (including triangular face, bifrontal narrowness, deeply set eyes, low-set/cupped ears, prominent nose, short philtrum, and thin upper lip with tented morphology) that can be evident from birth. Additional manifestations reported in some patients include large joint contractures and pectus excavatum (which become more evident with age) and seizures.

614
(68.1%)

PEHO syndrome

Abnormality of upper lip Epicanthus Malar flattening Tapered finger

Autosomal dominant inheritance Autosomal recessive inheritance

PEHO (Progressive encephalopathy with Edema, Hypsarrhythmia and Optic atrophy) syndrome is a rare neurodegenerative disorder belonging to the group of infantile progressive encephalopathies.

617
(68.0%)

Low isolated anorectal malformation

Absent radius Bifid scrotum

Low anorectal malformation is a rare, genetic, non-syndromic subtype of anorectal malformation, resulting from a developmental defect during embryogenesis, characterized by a wide spectrum of anorectal anomalies lying below the ischial tuberosity (e.g., anovestibular fistula in female, perineal and anocutaneous fistulas, and anal stenosis). Patients may present with failure to pass meconium, failure to thrive, and chronic constipation.

617
(68.0%)

Auriculoosteodysplasia

Aplasia/Hypoplasia of the radius Macrotia

Autosomal dominant inheritance

A very rare condition characterized by multiple osseous dysplasia, characteristic ear shape (elongation of the lobe that is attached and accompanied by a small, slightly posterior lobule) and somewhat short stature.

617
(68.0%)

Kuskokwim syndrome

Abnormal clavicle morphology Aplasia/Hypoplasia of the patella Aplasia/Hypoplasia of the radius

A very rare congenital contracture disorder, reported exclusively in Yup'ik Eskimos of the Kuskokwim River delta region of Alaska, characterized by multiple contractures of large joints (predominantly the knees and ankles) that present at birth or during childhood but are lifelong; deformities of the spine, pelvis and feet; and sometimes proximally or distally displaced patellae and muscle atrophy in the limbs with contractures. Additional radiological features include mild vertebral wedging, elongation of the vertebral pedicle, and clubbing of the distal clavicle. An autosomal recessive pattern of inheritance has been suggested.

617
(68.0%)

High isolated anorectal malformation

Absent radius Bifid scrotum

High anorectal malformation is a rare, genetic, non-syndromic subtype of anorectal malformation, resulting from a developmental defect during embryogenesis, characterized by a wide spectrum of anorectal anomalies, with or without a rectourogenital fistula, located above the pubococcygeal line (i.e. anorectal agenesis, rectal agenesis, atresia, or stenosis). Patients may present with meconuria, pyuria, strangury, and fecal and urinary incontinence.

617
(68.0%)

46,XX disorder of sex development-anorectal anomalies syndrome

Aplasia/Hypoplasia of the radius Multicystic kidney dysplasia

46,XX disorder of sex development-anorectal anomalies syndrome is a rare developmental defect during embryogenesis syndrome characterized by a normal female karyotype, normal ovaries, male or ambiguous genitalia, urinary tract malformations (ranging from bilateral renal agenesis to mild unilateral hydronephrosis), Müllerian duct anomalies (e.g. complete absence of the uterus and vagina, bicornuate uterus), and imperforate anus. Additional features may include tracheoesophageal fistula, radial aplasia, and malrotation of the gut.

617
(68.0%)

Atresia of urethra

Absent radius Neurogenic bladder

Aa rare congenital bladder outlet obstruction, a fetal lower urinary tract obstruction (fetal LUTO), that is usually fatal. Unless there is some other egress for the urine to escape the bladder, such as patent urachus or anuro-rectal communication, these lesions are not compatible with renal development.

623
(68.0%)

Deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome

Abnormality of the dentition Abnormality of the metacarpal bones Epicanthus Short hallux

Deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome is characterised by sensorineural deafness, bilateral synostosis of the 4th and 5th metacarpals and metatarsals, genital anomalies (hypospadias in males), psychomotor delay and abnormal dermatoglyphics. So far, it has been described in two unrelated patients. Facial dysmorphism was noted in both patients (prominent forehead, ear anomalies, facial asymmetry and an open mouth appearance).

624
(68.0%)

Laurin-Sandrow syndrome

Abnormality of the nose Absent radius Aplasia/Hypoplasia of the thumb Downturned corners of mouth

Autosomal dominant inheritance

Laurin-Sandrow syndrome (LSS) is characterised by complete polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella), often associated with ulnar and/or fibular duplication (and sometimes tibial agenesis). It has been described in less than 20 cases. Some cases with the same clinical signs but without nasal defects have also been reported, and may represent the same entity. The etiology of LSS is unknown. Different modes of inheritance have been suggested.

625
(67.9%)

Duplication/inversion 15q11

Brachycephaly Brachydactyly Clinodactyly of the 5th finger Downslanted palpebral fissures Short philtrum

The duplication/inversion 15q11 or isodicentric 15 chromosome (inv dup(15) or idic(15)) syndrome is a chromosomal disorder with distinctive clinical findings characterized by early central hypotonia, developmental delay and intellectual deficit, epilepsy, and autistic behavior.

625
(67.9%)

Alpha-thalassemia-X-linked intellectual disability syndrome

Brachydactyly Clinodactyly of the 5th finger Epicanthus Microcephaly Tented upper lip vermilion

X-linked recessive inheritance X-linked dominant inheritance

X-linked alpha thalassaemia mental retardation (ATR-X) syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal.

627
(67.9%)

Dysmorphism-cleft palate-loose skin syndrome

Cleft palate Epicanthus Micrognathia

Dysmorphism-cleft palate-loose skin syndrome is a rare, genetic developmental defect during embryogenesis characterized by severe psychomotor delay, intellectual disability, congenital, symmetrical circumferential skin creases of arms and legs, cleft palate, and facial dysmorphism (incl. elongated face, high forehead, blepharophimosis, short palpebral fissures, microphthalmia, microcornea, epicanthic folds, telecanthus, microtia, posteriorly angulated ears, broad nasal bridge, microstomia and micrognathia). Additional features reported include short stature, microcephaly, hypotonia, pectus excavatum, severe scoliosis, hypoplastic scrotum, and mixed hearing loss.

627
(67.9%)

Isotretinoin-like syndrome

Cleft palate Micrognathia Upslanted palpebral fissure

Autosomal recessive inheritance

Isotretinoin-like syndrome is a phenocopy of the isotretinoin embryopathy.

627
(67.9%)

Double outlet right ventricle

Cleft palate Epicanthus Micrognathia

Double outlet right ventricle (DORV) is a rare cono-truncal anomaly in which both the aorta and pulmonary artery originate, either entirely or predominantly, from the morphologic right ventricle.

630
(67.9%)

Böök syndrome

Abnormal eyebrow morphology Abnormality of the dentition Small hand

Autosomal dominant inheritance

Book syndrome is a rare autosomal dominant ectodermal dysplasia syndrome reported in a Swedish family (25 cases from 4 generations), and one isolated case, and is characterized by premolar aplasia, hyperhidrosis, and premature graying of the hair. Additional features reported in the isolated case include a narrow palate, hypoplastic nails, eyebrow anomalies, a unilateral simian crease, and poorly formed dermatoglyphics.

631
(67.8%)

Acrodysostosis with multiple hormone resistance

Absent/hypoplastic paranasal sinuses Malar flattening Short metacarpal Short metatarsal

632
(67.8%)

Catel-Manzke syndrome

Abnormality of epiphysis morphology Cleft palate Clinodactyly of the 5th finger Highly arched eyebrow Micrognathia

Autosomal recessive inheritance

Catel-Manzke syndrome is a rare bone disease characterized by bilateral hyperphalangy and clinodactyly of the index finger typically in association with Pierre Robin sequence (see this term) comprising micrognathia, cleft palate and glossoptosis.

633
(67.8%)

Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome

Abnormality of the metaphysis Downslanted palpebral fissures Malar flattening Tapered finger Thin vermilion border

X-linked recessive inheritance

A rare constitutional hemolytic anemia that is characterised by the association of Alport syndrome, midface hypoplasia, intellectual deficit and elliptocytosis. It has been described in two families. The syndrome is transmitted as an X-linked trait is caused by a contiguous gene deletion in Xq22.3 involving several genes including COL4A5, FACL4 and AMMECR1.

634
(67.8%)

Hidrotic ectodermal dysplasia

Conjunctivitis Small hand Sparse eyelashes

Autosomal dominant inheritance

Clouston syndrome (or hidrotic ectodermal dysplasia) is characterised by the clinical triad of nail dystrophy, alopecia, and palmoplantar hyperkeratosis.

634
(67.8%)

Pachydermoperiostosis

Blepharitis Coarse facial features Small hand

Pachydermoperiostosis (PDP) is a form of primary hypertrophic osteoarthropathy (see this term), a rare hereditary disorder, and is characterized by digital clubbing, pachydermia and subperiosteal new bone formation associated with pain, polyarthritis, cutis verticis gyrata, seborrhea and hyperhidrosis. Three forms have been described: a complete form with pachydermia and periostitis, an incomplete form with evidence of bone abnormalities but lacking pachydermia, and a forme frusta with prominent pachydermia and minimal-to-absent skeletal changes.

636
(67.8%)

Multiple epiphyseal dysplasia type 4

Cleft palate Small hand

Autosomal recessive inheritance

Multiple epiphyseal dysplasia type 4 is a multiple epiphyseal dysplasia with a late-childhood onset, characterized by joint pain involving hips, knees, wrists, and fingers with occasional limitation of joint movements, deformity of hands, feet, and knees (club foot, clinodactyly, brachydactyly), scoliosis and slightly reduced adult height. Radiographs display flat epiphyses with early arthritis of the hip, and double-layered patella. Multiple epiphyseal dysplasia type 4 follows an autosomal recessive mode of transmission. The disease is allelic to diastrophic dwarfism, atelosteogenesis type 2 and achondrogenesis type 1B with whom it forms a clinical continuum.

636
(67.8%)

Oculo-palato-cerebral syndrome

Cleft palate Short foot Small hand

Autosomal recessive inheritance

Oculopalatocerebral syndrome is characterised by the association of four anomalies: intellectual deficit, microcephaly, palate anomalies and ocular abnormalities.

638
(67.8%)

Plasmacytoma

Cheilitis Dacryocystitis Missing ribs

Plasmacytoma is a localized mass of neoplastic monoclonal plasma cells that represents approximately 5% of all plasma cell neoplasms. There are two separate entities: primary plasmacytoma of the bone and extramedullary plasmacytoma of the soft tissues. Of the extramedullary plasmacytomas, 80% occur in the head and neck, usually in the upper respiratory tract. The median age at diagnosis is 50 years and the male to female ratio is 3:1. Long-term survival is possible following local radiotherapy, particularly for soft tissue presentations.

639
(67.7%)

Kyphomelic dysplasia

Flat face Large hands Micrognathia Micromelia

Autosomal recessive inheritance

A rare primary bone dysplasia characterized, radiologically, by short, stubby long bones, severely angulated femurs and lesser bowing of other long bones (mild, moderate or no bowing), short and wide illiac wings with horizontal acetabular roofs, platyspondyly and a narrow thorax, clinically manifesting with severe, disproportionate short stature. Regression of femora angulation is observed with advancing age.

640
(67.7%)

Brachydactyly-arterial hypertension syndrome

Hypertension Short metacarpal

Autosomal dominant inheritance

Brachydactyly - arterial hypertension is a rare genetic brachydactyly syndrome characterized by the association of brachydactyly type E (see this term) with hypertension (due to vascular or neurovascular anomalies) as well as the additional features of short stature and low birth weight (compared to non-affected family members), stocky build and a round face. The onset of hypertension is often in childhood and, if untreated, most patients will have had a stroke by the age of 50.

640
(67.7%)

Talo-patello-scaphoid osteolysis

Enlarged joints Short 4th metacarpal

Autosomal recessive inheritance

Talo-patello-scaphoid osteolysis is an extremely rare form of primary osteolysis (see this term), described in two sisters to date, characterized by bilateral osteolysis of the tali, scaphoids, and patellae (accompanied by periarticular swelling and pain) and short fourth metacarpals (brachydactyly type E; see this term), in the absence of renal disease. Autosomal recessive inheritance has been suggested.

642
(67.7%)

X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome

Bilateral single transverse palmar creases Mandibular prognathia Short philtrum Synophrys

X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome is characterized by moderate intellectual deficit, bilateral single palmar creases, seizures, variable hypogammaglobulinemia and characteristic features (synophrys, prognathism, and hirsutism). It has been reported in three males from two generations of one family. All underwent progressive neurological deterioration. This syndrome is transmitted as an X-linked trait, and the causative gene is located between Xq21.33 and Xq23.

643
(67.7%)

Mowat-Wilson syndrome

Broad hallux phalanx Cleft upper lip Epicanthus Microcephaly Tapered finger

Autosomal dominant inheritance

Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, intellectual disability, epilepsy, Hirschsprung disease (HSCR; see this term) and variable congenital malformations.

644
(67.7%)

Wolcott-Rallison syndrome

Abnormality of the metaphysis Brachydactyly Epicanthus Microcephaly Thin vermilion border

Autosomal recessive inheritance

Wolcott-Rallison syndrome (WRS) is a very rare genetic disease, characterized by permanent neonatal diabetes mellitus (PNDM) with multiple epiphyseal dysplasia and other clinical manifestations, including recurrent episodes of acute liver failure.

645
(67.7%)

3MC syndrome

Craniosynostosis Downslanted palpebral fissures Oral cleft Radioulnar synostosis

3MC syndrome describes a rare developmental disorder, that unifies the overlapping autosomal recessive disorders previously known as Carnevale, Mingarelli, Malpuech and Michels syndromes, characterized by a spectrum of developmental anomalies that include distinctive facial dysmorphism (i.e. hypertelorism, blepharophimosis, blepharoptosis, highly arched eyebrows), cleft lip and/or palate, craniosynostosis, learning disability, radioulnar synostosis and genital and vesicorenal anomalies. Less common features reported include anterior chamber defects, cardiac anomalies (e.g. ventricular septal defect; see this term), caudal appendage, umbilical hernia/omphalocele and diastasis recti.

646
(67.7%)

Penoscrotal transposition

Epicanthus Micrognathia Patellar aplasia

Penoscrotal transposition (PST) is a rare congenital genital anomaly in which the scrotum is positioned superior and anterior to the penis. PST may present with a broad spectrum of anomalies ranging from simple shawl scrotum (doughnut scrotum) to very complex extreme transposition with craniofacial, central nervous system, cardiac, gastrointestinal, urological, and other genital (undescended testicles, hypospadias, chordee) malformations. Growth deficiency and intellectual disability may also be noticed (60% of cases).

647
(67.7%)

Ectodermal dysplasia-intellectual disability-central nervous system malformation syndrome

Cleft palate Epicanthus Retrognathia Sandal gap

X-linked recessive inheritance

Ectodermal dysplasia-intellectual disability-central nervous system malformation syndrome is a rare, multiple developmental anomalies syndrome characterized by the triad of ectodermal dysplasia (mostly hypohidrotic with dry skin and reduced sweating and sparse, fair scalp hair, eyebrows and eyelashes), severe intellectual disability and variable central nervous system anomalies (cerebellar hypoplasia, dilatation of ventricles, corpus callosum agenesis, Dandy-Walker malformation). Distinct craniofacial dysmorphism with macrocephaly, frontal bossing, midfacial hypoplasia and high arched or cleft palate, as well as cryptorchidism, feeding difficulties and hypotonia, are associated. There have been no further descriptions in the literature since 1998.

648
(67.6%)

Porencephaly

Dacryocystitis Hemiatrophy Micrognathia Sialadenitis

A rare, genetic or acquired, cerebral malformation characterized by an intracerebral fluid-filled cyst or cavity with or without communication between the ventricle and subarachnoid space. Clinical manifestations depend on location and severity and may include hemiparesis, seizures, intellectual disability, and dystonia.

649
(67.6%)

Microcephaly-albinism-digital anomalies syndrome

Microcephaly Micrognathia Short distal phalanx of finger

Microcephaly - albinism - digital anomalies syndrome is a very rare syndrome associating microcephaly, micrognathia, oculocutaneous albinism, hypoplasia of the distal phalanx of fingers and agenesia of the distal end of the right big toe.

650
(67.6%)

Joubert syndrome

Hand polydactyly Highly arched eyebrow Micrognathia Oral cleft

Joubert syndrome (JS) is characterized by congenital malformation of the brainstem and agenesis or hypoplasia of the cerebellar vermis leading to an abnormal respiratory pattern, nystagmus, hypotonia, ataxia, and delay in achieving motor milestones.

651
(67.5%)

Dyssegmental dysplasia, Silverman-Handmaker type

Cleft palate Micrognathia Micromelia

Autosomal recessive inheritance

Dyssegmental dysplasia, Silverman-Handmaker type is a rare, genetic, primary bone dysplasia disorder, and lethal form of neonatal short-limbed dwarfism, characterized by anisospondyly, severe short stature and limb shortening, metaphyseal flaring and distinct dysmorphic features (i.e. flat facial appearance, abnormal ears, short neck, narrow thorax). Additional features may include other skeletal findings (e.g. joint contractures, bowed limbs, talipes equinovarus) and urogenital and cardiovascular abnormalities.

651
(67.5%)

Kniest dysplasia

Cleft palate Glossoptosis Micrognathia Micromelia

Autosomal dominant inheritance

Kniest dysplasia is a severe type II collagenopathy characterized by a short trunk and limbs, prominent joints and midface hypoplasia (round face with a flat nasal root).

653
(67.5%)

Iniencephaly

Mandibular aplasia Narrow mouth Oral cleft Rhizomelia

Iniencephaly is a rare form of neural tube defect in which a malformation of the cervico-occipital junction is associated with a malformation of the central nervous system.

654
(67.5%)

H syndrome

Cleft upper lip Hallux valgus Shallow orbits Upper eyelid edema

Autosomal recessive inheritance

A rare cutaneous disease and a systemic inherited histiocytosis mainly characterized by hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height, and occasionally, hyperglycemia/diabetes mellitus. Due to overlapping clinical features, it is now considered to include pigmented hypertrichosis with insulin dependent diabetes mellitus syndrome (PHID), Faisalabad histiocytosis (FHC) and familial sinus histiocytosis with massive lymphadenopathy (FSHML). Some cases of dysosteosclerosis may also represent the syndrome.

655
(67.5%)

Aicardi-Goutières syndrome

Chilblains Eyelid coloboma Microcephaly

An inherited, subacute encephalopathy characterised by the association of basal ganglia calcification, leukodystrophy and cerebrospinal fluid (CSF) lymphocytosis.

656
(67.4%)

Autosomal dominant spondylocostal dysostosis

Cleft palate Missing ribs Upslanted palpebral fissure

A very rare and mild form of spondylocostal dysostosis characterized by vertebral and costal segmentation defects, often with a reduction in the number of ribs.

657
(67.4%)

Acrocardiofacial syndrome

Abnormality of the metacarpal bones Camptodactyly of finger Cleft palate Cleft upper lip Long eyelashes

Autosomal recessive inheritance

A rare genetic disorder characterized by split-hand/split-foot malformation (SHFM), facial anomalies, cleft lip/palate, congenital heart defect (CHD), genital anomalies, and intellectual deficit.

658
(67.3%)

Cortical blindness-intellectual disability-polydactyly syndrome

Abnormal palate morphology Long philtrum Microretrognathia Postaxial hand polydactyly

Autosomal recessive inheritance

A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by congenital, total, cortical blindness, intellectual disability, postaxial polydactyly of the hands and feet, pre- and postnatal growth delay, psychomotor developmental retardation, and mild facial dysmorphism (incl. prominent forehead, short nose, long philtrum, high-arched palate, and microretrognathia). Recurrent respiratory and intestinal infections, as well as moderate hypertonia and hyperreflexia, are also associated. There have been no further descriptions in the literature since 1985.

658
(67.3%)

Crisponi syndrome

Bilateral camptodactyly Long philtrum Micrognathia Narrow mouth

Autosomal recessive inheritance

Crisponi syndrome (CS) is a severe disorder characterized by muscular contractions at birth, intermittent hyperthermia, facial abnormalities and camptodactyly.

658
(67.3%)

Infantile-onset X-linked spinal muscular atrophy

Adducted thumb Long philtrum Micrognathia Open mouth

X-linked recessive inheritance

X-linked distal arthrogryposis multiplex congenital (SMAX2) is a rare form of spinal muscular atrophy characterized by the neonatal onset of severe hypotonia, areflexia, profound weakness, multiple congenital contractures, facial dysmorphic features (myopathic face with open, tent-shaped mouth), cryptorchidism, and mild skeletal abnormalities (i.e. kyphosis, scoliosis), that is often preceded by polyhydramnios and reduced fetal movements in utero and followed by bone fractures shortly after birth. SMAX2 patients often have a limited life span, often succumbing to the disease within 2 years, as muscle weakness is progressive and chest muscle involvement eventually leads to ventilatory insufficiency and respiratory failure.

658
(67.3%)

Cataract-intellectual disability-hypogonadism syndrome

High palate Micrognathia Short philtrum Ulnar deviation of finger

Autosomal recessive inheritance

This syndrome is characterized by the association of intellectual deficit, congenital cataract, and hypogonadotropic hypogonadism.

658
(67.3%)

PLAA-associated neurodevelopmental disorder

High palate Micrognathia Postaxial hand polydactyly Smooth philtrum

663
(67.3%)

Langer mesomelic dysplasia

Abnormality of the ulna High palate Micromelia Short metacarpal

Autosomal recessive inheritance

A rare disorder characterized by severe disproportionate short stature with mesomelic and rhizomelic shortening of the upper and lower limbs.

664
(67.3%)

Metaphyseal acroscyphodysplasia

Brachydactyly Epicanthus Micromelia Short toe

Autosomal recessive inheritance

Metaphyseal acroscyphodysplasia is an extremely rare form of metaphyseal dysplasia characterized by the distinctive radiological sign of cone-shaped upper tibial and lower femoral epiphyses embedded in large cup-shaped metaphyses, associated with short stature and micromelia. Upper limb involvement includes brachydactyly and phalangeal and metacarpal cone-shaped epiphyses. The association of metaphyseal acroscyphodysplasia with psychomotor delay and alopecia has also been reported in some cases.

665
(67.3%)

Campomelia, Cumming type

Brachydactyly Cleft palate Micromelia

Autosomal recessive inheritance

Campomelia, Cumming type, is characterized by the association of limb defects and multivisceral anomalies.

666
(67.2%)

Familial osteodysplasia, Anderson type

Aplasia/hypoplasia of the femur Carious teeth Missing ribs Thick eyebrow

Familial osteodysplasia, Anderson type is a rare, genetic dysostosis disorder characterized by craniofacial bone abnormalities (i.e. midface hypoplasia, broad, flat nasal bridge, narrow, thin prognathic mandible with pointed chin, malocclusion, partial dental agenesis) associated with additional osseous anomalies, including scoliosis, calvarial thinning, pointed spinous processes, clinodactyly and abnormal phalanges. Elevated erythrocyte sedimentation rate, hyperuricemia and hypertension have also been reported. There have been no further descriptions in the literature since 1982.

667
(67.2%)

SPONASTRIME dysplasia

Malar flattening Mesomelia Thick vermilion border

Autosomal recessive inheritance

A rare, genetic, spondyloepimetaphyseal dysplasia disease characterized by short-limbed short stature (more pronounced in lower limbs) associated with characterisitic facial dysmorphism (i.e. relative macrocephaly, frontal bossing, midface hypoplasia, depressed nasal root, small upturned nose, prognathism) and abnormal radiological findings, which include abnormal vertebral bodies (particularly in the lumbar region), striated metaphyses, generalized mild osteoporosis, and delayed ossification of the carpal bones. Progressive coxa vara, short dental roots, hypogammaglobulinemia and cataracts may be occasionally associated.

668
(67.1%)

Neurogenic arthrogryposis multiplex congenita

Aplasia/Hypoplasia of the radius Micrognathia Round face

Autosomal recessive inheritance

Neurogenic arthrogryposis multiplex congenita is a form of arthrogryposis multiplex congenita characterized by congenital immobility of the limbs with fixation of multiple joints and muscle wasting. This condition is secondary to neurogenic muscular atrophy.

669
(67.1%)

Metatropic dysplasia

Cleft palate Clinodactyly of the 5th finger Hypoplastic cervical vertebrae Micromelia

Autosomal dominant inheritance

Metatropic dysplasia (MTD) is a rare spondyloepimetaphyseal dysplasia characterized by a long trunk and short limbs in infancy followed by severe and progressive kyphoscoliosis causing a reversal in proportions during childhood (short trunk and long limbs) and a final short stature in adulthood.

670
(67.1%)

Microcephaly-brachydactyly-kyphoscoliosis syndrome

Broad thumb Downslanted palpebral fissures High, narrow palate Malar flattening

Microcephaly-brachydactyly-kyphoscoliosis syndrome is characterized by profound intellectual deficit in association with microcephaly, short stature, brachydactyly type D, a flattened occiput, downslanting palpebral fissures, low-set large ears, a broad prominent nose and kyphoscoliosis. It has been described in three sisters. The disorder is likely to be transmitted as an autosomal recessive trait.

671
(67.1%)

Mucopolysaccharidosis type 1

Abnormality of the metaphysis Cicatricial entropion Sinusitis Split hand Thick lower lip vermilion

Mucopolysaccharidosis type 1 (MPS 1) is a rare lysosomal storage disease belonging to the group of mucopolysaccharidoses. There are three variants, differing widely in their severity, with Hurler syndrome being the most severe, Scheie syndrome the mildest and Hurler-Scheie syndrome giving an intermediate phenotype.

672
(67.1%)

Sarcoidosis

Cheilitis Cicatricial entropion Finger swelling Palmar pits Sinusitis

Sarcoidosis is a multisystemic disorder of unknown cause characterized by the formation of immune granulomas in involved organs.

673
(67.1%)

Fibular aplasia-ectrodactyly syndrome

Abnormality of the ulna Aplasia/Hypoplasia of the fibula Split hand

Autosomal dominant inheritance

A rare disorder characterized by fibular aplasia and ectrodactyly. Less than 50 familial and sporadic cases have been reported in the literature. Shortening of the femur, a curved tibia, severe foot anomalies and pathologies of the hip, knee and ankle may also be present. The disorder is probably inherited as an autosomal dominant trait, with reduced penetrance, especially in females.

673
(67.1%)

Boomerang dysplasia

Abnormality of the ulna Aplasia/Hypoplasia of the fibula Cryptorchidism Micromelia

Autosomal dominant inheritance

Boomerang dysplasia (BD) is a rare lethal skeletal dysplasia characterized by severe short-limbed dwarfism, dislocated joints, club feet, distinctive facies and diagnostic x-ray findings of underossified and dysplastic long tubular bones, with a boomerang-like bowing.

675
(67.0%)

Developmental malformations-deafness-dystonia syndrome

Hypoplastic scapulae Macroglossia Micromelia Oral cleft

Autosomal dominant inheritance

Developmental malformations-deafness-dystonia syndrome is characterised by the association of midline malformations, sensory hearing loss, and a delayed-onset generalised dystonia syndrome.

676
(67.0%)

Auricular abnormalities-cleft lip with or without cleft palate-ocular abnormalities syndrome

Incomplete cleft of the upper lip Micrognathia Oral cleft

The association of auricular abnormalities and cleft lip with or without cleft palate has been described in two siblings. One sibling had postauricular pits, profound myopia, nystagmus and retinal pigment abnormalities. The second sibling was a fetus (gestational age: 23 weeks) with severe cleft lip, cleft palate and external ear abnormalities.

676
(67.0%)

Lethal osteosclerotic bone dysplasia

Gingival fibromatosis Median cleft lip and palate Micrognathia

Autosomal recessive inheritance

A rare disorder defined by generalized osteosclerosis with periosteal bone formation, characteristic facial dysmorphism, brain abnormalities including intracerebral calcifications, and neonatal lethal course.

676
(67.0%)

Triploidy

Micrognathia Non-midline cleft lip Wide mouth

Triploidy is a rare chromosomal anomaly, polyploidy, characterized by early in utero growth restriction, and multiple birth defects, including neural tube defects, facial abnormalities, cleft lip/palate, congenital heart anomalies, genital malformations, and peripheral skeletal abnormalities. It is usually prenatally lethal.

679
(67.0%)

Scalp-ear-nipple syndrome

Abnormality of the dentition Eyelid coloboma Syndactyly

Autosomal dominant inheritance

A rare syndrome characterised by the following triad: areas of hairless raw skin over the scalp (present at birth and healing during childhood), prominent, hypoplastic ears with almost absent pinnae, and bilateral amastia. Renal and urinary tract abnormalities, as well as cataract, have also been observed.

680
(67.0%)

17q23.1q23.2 microdeletion syndrome

Epicanthus Narrow mouth Patellar hypoplasia

Sporadic

17q23.1q23.2 microdeletion syndrome is a recently described syndrome characterized by developmental delay, microcephaly, short stature, heart defects and limb abnormalities.

681
(67.0%)

Neurofibromatosis type 2

Nasal obstruction Retinal hamartoma Small finger

Autosomal dominant inheritance

Neurofibromatosis type 2 (NF2) is a tumor-prone disorder characterized by the development of multiple schwannomas and meningiomas.

682
(67.0%)

Syndactyly type 4

Hand polydactyly Short tibia

Autosomal dominant inheritance

Syndactyly type 4 (SD4) is a very rare congenital distal limb malformation characterized by complete bilateral syndactyly (involving all digits 1 to 5).

682
(67.0%)

Autosomal recessive axonal neuropathy with neuromyotonia

Hyperhidrosis Short third metatarsal

Autosomal recessive inheritance

A rare peripheral neuropathy characterized by slowly progressive axonal, motor greater than sensory, polyneuropathy combined with neuromytonia (including spontaneous muscular activity at rest (myokymia), impaired muscle relaxation (pseudomyotonia), and contractures of hands and feet) and neuromyotonic or myokymic discharges on needle EMG. It presents with distal lower limb weakness with gait impairment, muscle stiffness, fasciculations and cramps in hands and legs worsened by cold, decreased to absent tendon reflexes, intrinsic hand muscle atrophy and, variably, mild distal sensory impairment.

684
(67.0%)

XK aprosencephaly syndrome

Abnormal morphology of the radius Narrow mouth Phocomelia

Autosomal recessive inheritance

XK aprosencephaly syndrome is a very rare syndromic type of cerebral malformation characterized by aprosencephaly (absence of telencephalon and diencephalon), oculo-facial anomalies (i.e. ocular hypotelorism or cyclopia, malformation/absence of nasal structures, cleft lip), preaxial limb defects (i.e. hypoplastic hands, absent halluces) and various other anomalies including ambiguous genitalia, imperforate anus, and vertebral anomalies. The syndrome is thought to have an autosomal recessive mode of inheritance.

685
(66.9%)

Hereditary acrokeratotic poikiloderma

Abnormality of the metacarpal bones Camptodactyly of finger Ectropion Narrow mouth Trismus

686
(66.9%)

Nance-Horan syndrome

Abnormality of the dentition Mandibular prognathia Short metacarpal

X-linked dominant inheritance

Nance-Horan syndrome (NHS) is characterized by the association in male patients of congenital cataracts with microcornea, dental anomalies and facial dysmorphism.

687
(66.9%)

16p13.11 microdeletion syndrome

Camptodactyly of finger Cleft upper lip Downslanted palpebral fissures Microcephaly

16p13.11 microdeletion syndrome is a recently described syndrome characterized by developmental delay, microcephaly, epilepsy, short stature, facial dysmorphism and behavioral problems.

687
(66.9%)

Branchio-oculo-facial syndrome

Dolichocephaly Non-midline cleft lip Preaxial hand polydactyly Telecanthus

Autosomal dominant inheritance

Branchio-oculo-facial syndrome (BOFS) is characterised by low birth weight and growth retardation, bilateral branchial clefts that may be hemangiomatous, sometimes with linear skin lesions behind the ears ('burn-like' lesions), congenital strabismus, obstructed nasolacrimal ducts, a broad nasal bridge with a flattened nasal tip, a protruding upper lip with an unusually broad and prominent philtrum, and full mouth.

689
(66.9%)

Acrogeria

Convex nasal ridge Hypodontia Micrognathia Small hand

689
(66.9%)

Central precocious puberty

Micrognathia Small hand Tongue nodules

Central precocious puberty (CPP), also referred to as gonadotropin dependent precocious puberty, is an endocrine-related developmental disease characterized by the onset of pubertal changes, with development of secondary sexual characteristics and accelerated growth and bone maturation, before the normal age of puberty (8 years in girls and 9 years in boys).

689
(66.9%)

Autosomal dominant spastic paraplegia type 17

Microdontia Micrognathia Small hand Triangular face

Autosomal dominant inheritance

A complex hereditary spastic paraplegia characterized by progressive spastic paraplegia, upper and lower limb muscle atrophy, hyperreflexia, extensor plantar responses, pes cavus and occasionally impaired vibration sense. Association with hand muscles amyotrophy typical.

692
(66.9%)

Beta-mercaptolactate cysteine disulfiduria

Arachnodactyly Downslanted palpebral fissures High palate Micromelia

Autosomal recessive inheritance

An extremely rare disorder of methionine cycle and sulfur amino acid metabolism characterized by increased urine excretion of beta-mercaptolactate-cysteine disulfide (due to deficiency of mercaptopyruvate sulfurtransferase activity in erythrocytes), leading to a positive cyanide nitroprusside test. Association with intellectual disability, congenital lens dislocation, and behavioral abnormalities has been reported, however the causal link remains to be established. There have been no further descriptions in the literature since 1981.

692
(66.9%)

X-linked dominant chondrodysplasia punctata

Abnormality of the dentition Clinodactyly of the 5th finger Epicanthus Rhizomelia

X-linked dominant chondrodysplasia punctata (CDPX2) is a rare genodermatosis with great phenotypic variation and characterized most commonly by ichthyosis, chondrodysplasia punctata (CDP), asymmetric shortening of the limbs, cataracts and short stature.

692
(66.9%)

Ito hypomelanosis

Abnormality of the dentition Hemiatrophy Triphalangeal thumb Upslanted palpebral fissure

Autosomal dominant inheritance Autosomal recessive inheritance X-linked recessive inheritance Heterogeneous Somatic mosaicism

Hypomelanosis of Ito (HI) is a multisystemic neurocutaneous condition with hypopigmented skin lesions along the Blaschko lines.

692
(66.9%)

Systemic lupus erythematosus

Blepharitis Chilblains Hemiatrophy Oral ulcer

696
(66.9%)

Filippi syndrome

Clinodactyly of the 5th finger Downslanted palpebral fissures Enlarged epiphyses Microcephaly Short philtrum

Autosomal recessive inheritance

Filippi syndrome is characterised by microcephaly, cutaneous syndactyly of the fingers and toes, intellectual deficit, growth retardation and a characteristic facies (high and broad nasal bridge, thin alae nasi, micrognathia and a high frontal hairline). So far, less than 25 cases have been reported. Cryptorchidism, polydactyly, and teeth and hair anomalies may also be present. Transmission is autosomal recessive.

697
(66.9%)

Monosomy 22q13

Dental crowding Epicanthus Large hands Malar flattening

Autosomal dominant inheritance Sporadic

Monosomy 22q13 syndrome (deletion 22q13.3 syndrome or Phelan-McDermid syndrome) is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features.

698
(66.9%)

Renal dysplasia

Micrognathia Potter facies Short 4th metacarpal

Renal dysplasia is a form of renal malformation in which the kidney(s) are present but their development is abnormal and incomplete. Renal dysplasia can be unilateral or bilateral (see these terms), segmental, and of variable severity, with renal aplasia corresponding to extreme dysplasia.

699
(66.9%)

Rhizomelic chondrodysplasia punctata

Abnormality of the dentition Epicanthus Rhizomelia

Rhizomelic chondrodysplasia is a form chondrodysplasia punctata (see this term), a group of diseases in which the common characteristic is calcifications near joints at birth.

700
(66.9%)

Acrofacial dysostosis, Weyers type

Abnormality of the dentition Overlapping fingers Small hand

Autosomal dominant inheritance

A rare ectodermal dysplasia syndrome with bone abnormalities characterized by onychodystrophy; anomalies of the lower jaw, oral vestibule and dentition; post-axialpolydactyly; moderately restricted growth with short limbs; and normal intelligence. Although it closely resembles Ellis-van Creveld syndrome (see this term), an allelic disorder and another type of ciliopathy, WAD is usually a milder disease without the presence of heart abnormalities and is inherited in an autosomal dominant manner.