Cleft palate, and Coarse facial features

Medium match HYPERTROPHIC OSTEOARTHROPATHY, PRIMARY, AUTOSOMAL RECESSIVE, 1; PHOAR1

Primary hypertrophic osteoarthropathy is a familial disorder characterized by digital clubbing and osteoarthropathy, with variable features of pachydermia, delayed closure of the fontanels, and congenital heart disease. Secondary hypertrophic osteoarthropathy, or pulmonary hypertrophic osteoarthropathy, is a different disorder characterized by digital clubbing secondary to acquired diseases, most commonly intrathoracic neoplasm (Uppal et al., 2008).Touraine et al. (1935) recognized pachydermoperiostosis as a familial disorder with 3 clinical presentations or forms: a complete form characterized by periostosis and pachydermia; an incomplete form with bone changes but without pachydermia; and a 'forme fruste' with pachydermia and minimal skeletal changes. Genetic HeterogeneityPHOAR2 (OMIM ) is caused by mutation in the SLCO2A1 gene (OMIM ) on chromosome 3q22.1-q22.2.Families with an autosomal dominant form of primary hypertrophic osteoarthropathy have also been reported (PHOAD ).

HYPERTROPHIC OSTEOARTHROPATHY, PRIMARY, AUTOSOMAL RECESSIVE, 1; PHOAR1 Is also known as pho, autosomal recessive|pachydermoperiostosis, autosomal recessive|pdp, autosomal recessive|touraine-solente-gole syndrome

• Growth delay
• Neoplasm
• Cleft palate
• Pain
• Ptosis

SOURCES: OMIM MENDELIAN

Medium match PLATYSPONDYLIC DYSPLASIA, TORRANCE TYPE

Platyspondylic lethal skeletal dysplasia (PLSD), Torrance type (PLSD-T) is a skeletal dysplasia characterised by severe limb shortening (short and broad long bones), platyspondyly with wafer-like vertebral bodies, short ribs with anterior cupping, severe hypoplasia of the lower ilia and radial bowing. Histological findings include slightly enlarged chondrocytes and hypercellularity. The prevalence is unknown. The disorder is transmitted as an autosomal dominant trait and is caused by mutations in the C-propeptide domain of the COL2A1 gene. Although PLSD-T is generally lethal, survival to adulthood has been reported in two families.

PLATYSPONDYLIC DYSPLASIA, TORRANCE TYPE Is also known as platyspondylic dysplasia, torrance-luton type|thanatophoric dysplasia, torrance variant|lethal short-limbed platyspondylic dwarfism, torrance type|platyspondylic lethal skeletal dysplasia, torrance type|plsd-t

• Cleft palate
• Low-set ears
• Depressed nasal bridge
• Macrocephaly
• Short neck

SOURCES: OMIM MESH ORPHANET MENDELIAN

Medium match SHORT-RIB THORACIC DYSPLASIA 13 WITH OR WITHOUT POLYDACTYLY; SRTD13

• Hypertelorism
• Cleft palate
• Cryptorchidism
• Respiratory insufficiency
• Microphthalmia

SOURCES: OMIM MENDELIAN

Medium match BECKWITH-WIEDEMANN SYNDROME DUE TO CDKN1C MUTATION

• Strabismus
• Cleft palate
• Cryptorchidism
• Hepatomegaly
• Ventricular septal defect

SOURCES: ORPHANET MENDELIAN

Medium match LETHAL POLYMALFORMATIVE SYNDROME, BOISSEL TYPE

Lethal polymalformative syndrome, Boissel type is a rare, genetic, lethal, multiple congenital anomalies/dysmorphic syndrome characterized by failure to thrive, severe developmental delay, severe postanatal microcephaly, frequent congenital cardiac defects and characteristic facial dysmorphysm (including coarse face with anteverted nostrils, thin vermillion, prominent alveolar ridge and retro- or micrognatia). Additional common features include neurologic abnormalities (hyper-/hypotonia, sensorineural deafness, hydrocephalus, cerebral atrophy, seizures), as well as brachydactyly, cutis marmorata and genital anomalies.

• Seizures
• Global developmental delay
• Hearing impairment
• Microcephaly
• Growth delay

SOURCES: MESH ORPHANET OMIM MENDELIAN

Medium match SIMPSON-GOLABI-BEHMEL SYNDROME, TYPE 2; SGBS2

An extremely rare and severe early-lethal form of Simpson-Golabi-Behmel syndrome. The disease is an overgrowth-multiple anomalies syndrome with characteristics of hydrops fetalis, macrocephaly, facial dysmorphism, short neck, redundant skin, skeletal defects (involving upper and lower limbs), hypoplastic nails, gastrointestinal and genitourinary anomalies, hypotonia and neurologic impairment. Severe intellectual disability, obesity and infections (pneumonia, sepsis) have been reported.

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Hypertelorism
• Abnormal facial shape

SOURCES: OMIM MESH ORPHANET MENDELIAN

Medium match HYPERPHOSPHATASIA-INTELLECTUAL DISABILITY SYNDROME

Hyperphosphatasia with mental retardation syndrome-1 is an autosomal recessive disorder characterized by mental retardation, various neurologic abnormalities such as seizures and hypotonia, and hyperphosphatasia. Other features include facial dysmorphism and variable degrees of brachytelephalangy (summary by Krawitz et al., 2010). The disorder is caused by a defect in glycosylphosphatidylinositol biosynthesis; see GPIBD1 (OMIM ). Genetic Heterogeneity of Hyperphosphatasia with Mental Retardation SyndromeSee also HPMRS2 (OMIM ), caused by mutation in the PIGO gene (OMIM ) on chromosome 9p13; HPMRS3 (OMIM ), caused by mutation in the PGAP2 gene (OMIM ) on chromosome 11p15; HPMRS4 (OMIM ), caused by mutation in the PGAP3 gene (OMIM ) on chromosome 17q12; HPMRS5 (OMIM ), caused by mutation in the PIGW gene (OMIM ) on chromosome 17q12; and HPMRS6 (OMIM ), caused by mutation in the PIGY gene (OMIM ) on chromosome 4q22.Knaus et al. (2018) provided a review of the main clinical features of the different types of HPMRS, noting that some patients have a distinct pattern of facial anomalies that can be detected by computer-assisted comparison, particularly those with mutations in the PIGV and PGAP3 genes. Individuals with HPMRS have variable increased in alkaline phosphatase (AP) as well as variable decreases in GPI-linked proteins that can be detected by flow cytometry. However, there was no clear correlation between AP levels or GPI-linked protein abnormalities and degree of neurologic involvement, mutation class, or gene involved. Knaus et al. (2018) concluded that a distinction between HPMRS and MCAHS (see, e.g., {614080}), which is also caused by mutation in genes involved in GPI biosynthesis, may be artificial and even inaccurate, and that all these disorders should be considered and classified under the more encompassing term of 'GPI biosynthesis defects' (GPIBD).

HYPERPHOSPHATASIA-INTELLECTUAL DISABILITY SYNDROME Is also known as mabry syndrome|glycosylphosphatidylinositol biosynthesis defect 2|gpibd2

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM ORPHANET MENDELIAN

Medium match OSTEOCRANIOSTENOSIS

Osteocraniostenosis is a lethal skeletal dysplasia characterized by a cloverleaf skull anomaly, facial dysmorphism, limb shortness, splenic hypo/aplasia and radiological anomalies including thin tubular bones with flared metaphyses and deficient calvarial mineralization.

OSTEOCRANIOSTENOSIS Is also known as habrodysplasia|osteocraniostenosis|gracile bone dysplasia|skeletal dysplasia, lethal, with gracile bones|osteocraniosplenic syndrome

• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM MESH ORPHANET MENDELIAN

Medium match COFFIN-SIRIS SYNDROME 6; CSS6

Coffin-Siris syndrome-6 is characterized by short stature, sparse hair, mild to severe intellectual disability, coarse facial features, and variable behavioral anomalies. Some patients have fifth digit clinodactyly with small nails. Other congenital anomalies and seizures may be present. This description is based on reports of 7 unrelated patients (Shang et al., 2015; Van Paemel et al., 2017; Bramswig et al., 2017).For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (OMIM ).

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM MENDELIAN

Medium match COFFIN-SIRIS SYNDROME

Coffin-Siris syndrome (CSS) is a rare congenital multi-systemic genetic disorder characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth digit, developmental delay, intellectual disability, coarse facial features, and other variable clinical manifestations.

COFFIN-SIRIS SYNDROME Is also known as css

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Hearing impairment

SOURCES: ORPHANET MENDELIAN