The proposita at age 16 years. A: Frontal view; (B) short ears, hypoplasia nasal alae, and micrognathia; (C) cutaneous mastocytosis; (D) the hands show camptodactyly of the right 5th finger and complete distal palmar crease at left; and (E) asymmetric small left foot. (Salpietro CD et al. Apparent third patient with cutaneous mastocytosis, microcephaly, conductive hearing loss, and microtia. Am. J. Med. Genet. 149A: 2270-2273, 2009)

Cutaneous mastocytosis, conductive hearing loss and microtia



 Abdominal pain (腹痛) [HP:0002027] [01420]
 Areflexia (無反射) [HP:0001284] [0242]
 Camptodactyly of finger (屈指) [HP:0100490] [15403]
 Clinodactyly of the 5th finger (第5指弯指) [HP:0004209] [15409]
 Conductive hearing impairment (伝音難聴) [HP:0000405] [0911]
 Delayed cranial suture closure (頭蓋骨縫合閉鎖遅延) [HP:0000270] [0331]
 Erythema (紅斑) [HP:0010783] [18008]
 Failure to thrive (成長障害) [HP:0001508] [01411]
 Generalized hyperpigmentation (不規則な高色素) [HP:0007440] [18017]
 High palate (高口蓋) [HP:0000218] [0821]
 Irregular hyperpigmentation (不規則な高色素) [HP:0007400] [18017]
 Macule (斑] [HP:0012733] [18007]
 Mastocytosis (肥満細胞症) [HP:0100495]
 Microcephaly (小頭) [HP:0000252] [03013]
 Micrognathia (小顎) [HP:0000347] [05401]
 Microtia (小耳) [HP:0008551] [090111]
 Muscular hypotonia (筋緊張低下) [HP:0001252] [0242]
 Optic atrophy (視神経萎縮) [HP:0000648] [06522]
 Papule (丘疹) [HP:0200034] [18007]
 Proptosis (眼球突出) [HP:0000520] [06603]
 Pruritus (掻痒) [HP:0000989] [18021]
 Seizures (けいれん) [HP:0001250] [01405]
 Short stature (低身長) [HP:0004322] [0130]
 Subcutaneous nodule (皮下結節] [HP:0001482] [18027]
 Thick lower lip vermilion (厚い下口唇唇紅部) [HP:0000179] [05522]
 Triangular face (三角顔) [HP:0000325] [0425]
 Upslanted palpebral fissure (眼瞼裂斜上) [HP:0000582] [0677]
 Urticaria (蕁麻疹) [HP:0001025] [18007]
 Ventriculomegaly (脳室拡大) [HP:0002119] [03010]
 Arrhythmia (不整脈) [HP:0011675] [01700]
 Fatigue (疲労) [HP:0012378] [01410]
 Hypotension (低血圧) [HP:0002615] [01416]
 Immunologic hypersensitivity (免疫学的過敏) [HP:0100326]
 Intellectual disability (知的障害) [HP:0001249] [0120]
 Irritability (被刺激性) [HP:0000737] [01418]
 Lichenification (苔癬化) [HP:0100725] [18019]
 Long nose (長い鼻) [HP:0003189] [0706]
 Lower limb asymmetry (下肢非対称) [HP:0100559] [1504]
 Pneumonia (肺炎) [HP:0002090] [014230]
 Prominent supraorbital ridges (目立つ眼窩上縁) [HP:0000336] [0511]
 Respiratory insufficiency (呼吸不全) [HP:0002093] [01606]
 Scoliosis (側弯) [HP:0002650] [161502]
 Severe global developmental delay (重度全般的発達遅滞) [HP:0011344] [0120]
 Skin vesicle (皮膚水泡) [HP:0200037] [18007]
 Telangiectasia of the skin (皮膚の毛細血管拡張] [HP:0100585] [18036]
 Thickened skin (肥厚した皮膚) [HP:0001072] [18019]
 Vomiting (嘔吐) [HP:0002013] [01425]
 Wide nasal bridge (幅広い鼻梁) [HP:0000431] [0703]
 Wide nose (幅広い鼻) [HP:0000445] [0703]
 Abnormality of metabolism/homeostasis (代謝-ホメオスターシス異常) [HP:0001939]
 Abnormality of skin pigmentation (皮膚色素異常) [HP:0001000] [-]
 Autosomal recessive inheritance (常染色体劣性遺伝) [HP:0000007]
 Cutaneous mastocytosis (皮膚肥満細胞症) [HP:0200151]
 Dermatographic urticaria (皮膚描画性蕁麻疹) [HP:0011971] [18007]
 Feeding difficulties (食餌摂取障害) [HP:0011968] [01411]
 Generalized hypotonia (全身性筋緊張低下) [HP:0001290] [0242]
 Underdeveloped nasal alae (鼻翼未発達) [HP:0000430] [0741]

 皮膚描画症 (皮膚描画性蕁麻疹)
(皮膚生検) 肥満細胞浸潤

Clinical Features
●Wolach ら(1990) は, 両親がいとこのSephardic ユダヤ人の5歳女児でこの組合わせを記載
 生検で diffuse cutaneous mastocytosis (154800) の診断が確定した
 Wolach ら(1990) は常染色体劣性遺伝を好んだ

Hennekam and Beemer (1992) studied a girl, born of nonconsanguineous parents in the Netherlands, who at birth was noted to have diffuse hyperpigmented, slightly elevated macules on her whole body, especially on the trunk and extremities, with exaggerated dermatographism. She had a large anterior fontanel, slight proptosis, upward slanting palpebral fissures, highly arched palate, receding chin, and clinodactyly of the fifth fingers. Neurologic examination revealed generalized hypotonia, decreased deep tendon reflexes, and absent swallowing reflex; she required lifelong feeding by gavage. Funduscopy showed slightly pale optic nerve heads, which remained unchanged over the next 8 years; visual evoked potentials were normal. She had bilateral mixed hearing loss of 60 to 70 dB. At 7 months of age, she began to have generalized seizures and continued to have 10 to 15 convulsions per day despite extensive antiseizure medication. She had very severe developmental retardation, reacting to tactile stimuli and able to smile, but with no other motor abilities. At 2 years of age, her length was in the 10th centile and weight in the 25th centile, and she remained in those centiles until her death at 8 years of age from bronchopneumonia. Hennekam and Beemer (1992) noted similarities to the patient described by Wolach et al. (1990).

Salpietro et al. (2009) reported a 16-year-old girl, born of nonconsanguineous parents, who at 3 years of age developed diffuse macules and papules on the neck and trunk, but did not have pruritus, feeding difficulties, or recurrent infections. She had mild mental retardation and hypotonia. Examination at 16 years of age revealed diffuse hyperpigmented macules and papules on the trunk, with fewer over the limbs; however, her face, scalp, palms, and soles were spared. Dermatographism was also present. She had microcephaly and a triangular face, with prominent supraorbital ridges, upward-slanting palpebral fissures, wide nasal bridge, long and prominent nose, hypoplastic nares, full lips, high-arched palate, micrognathia, bilateral short ears, long slender fingers, left complete distal palmar crease, camptodactyly of the right fifth finger, and small asymmetric feet, with the left foot being 2 cm shorter than the right. Laboratory studies, abdominal ultrasound, cardiologic evaluation, and ophthalmologic and audiologic examinations were all normal. Radiographs demonstrated a dislocation of the right proximal fifth finger interphalangeal joint, and skin biopsy showed prominent mast cell infiltration and confirmed the diagnosis of cutaneous mastocytosis. Salpietro et al. (2009) noted similarities to the patients previously reported by Wolach et al. (1990) and Hennekam and Beemer (1992), except for lack of feeding problems or hearing loss in the present patient.

(1) Wolach B et al. Skin mastocytosis with short stature, conductive hearing loss and microtia: a new syndrome. Clin Genet 37: 64-68, 1990
(2) Hennekam RCM, Beemer FA: Skin mastocytosis, hearing loss and mental retardation. Clin Dysmorph 1: 85-88, 1992